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being female, older age (per 10 y) & women on NNRTI predicted AEs requiring discontinuation (depression 23% of discontinuation due to AE)....older age (per 10 y) also predicted an AE causing a dose modification
JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 October 2010
Bhattacharya, Debika MD*; Umbleja, T MS; Carrat, F MD, PhD; Chung, R T MD; Peters, M G MD; Torriani, F MD; Andersen, J PhD; Currier, J S MD, MSc*. From the *University of California, Los Angeles, CA; Harvard School of Public Health, Boston, MA; UMR-S 707, UPMC-Paris 6 and INSERM; Saint-Antoine Hospital, APHP, Paris, France; Massachusetts General Hospital, Harvard University School of Medicine, Boston, MA; University of California, San Francisco, CA; and University of California, San Diego, CA.
"In conclusion, women are more likely to experience AEs, leading to hepatitis C treatment dose modification and discontinuation in the setting of HIV/HCV coinfection. Women on NNRTI regimens were more likely to discontinue therapy, and women on AZT-containing regimens were more likely to require dose modifications, suggesting an important sex-mediated role of ARV regimen on the impact of AEs during hepatitis C therapy. ARV regimen may be an important predictor of treatment discontinuation and modification in women and should be further explored as predictors of AEs in HIV/HCV coinfection trials.
Primary endpoints were AEs requiring treatment discontinuation (AETD) or first dose modification (AEDM).
Women were more likely to experience an AETD than men, 24% vs. 16% (P = 0.003).....female sex [odds ratio (OR) = 1.63] was a predictor of AETD. .....female sex was a predictor of AEDM (OR = 1.72)......Women were more likely to experience an AEDM than men, 61% vs. 48% (P < 0.0001)......Women discontinued therapy and required dose modification earlier than men......women experience some AEs (depression and anemia) more commonly than men.10,11.....Women on NNRTI-containing regimens were more likely to have an AETD than ARV-naive women or women on other ARV regimens (OR = 2.23), whereas in men, no association between NNRTI-containing regimen and AETD was observed. Of the 69 women with an AETD, depression was responsible for 16 of 69 AETDs (23%); women on NNRTI therapy were more likely to experience depression, 8 of 25 (32%) than those who were on other ARV or not on ARV 8 of 44 (18%); (P = 0.02).
The aim of our study was to investigate whether female sex was associated with an increased incidence and/or more rapid onset of AEs requiring treatment modification or discontinuation. In addition, we examined whether factors such as ARV regimen and BMI were important in predicting AEs in women and men.
We performed a meta-analysis of the AIDS Clinical Trials Group (ACTG) A5071, AIDS Pegasys Ribavirin International Coinfection Trial (APRICOT), and Agence Nationale de Recherches sur le SIDA (ANRS) HCO2-RIBAVIC HCV treatment studies in HIV/HCV coinfection, conducted by different clinical trial networks between 2000 and 2003.
Fifty-three percent of women vs. 67% of men completed study treatment as specified by the respective study protocol; 24% vs. 16% discontinued treatment early due to toxicities, 11% vs. 9% due to nonresponse, 9% vs. 6% due to other known reasons;
Adverse Events Requiring Treatment Discontinuation
Women were more likely to experience an AETD than men, 24% vs. 16% (P = 0.003). Primary etiologies of AETD among the 238 who experienced an AETD included constitutional or other symptoms in 176 (74%) and depression in 44 (18%). Discontinuation due to hematologic abnormalities was not common; anemia, thrombocytopenia, and neutropenia were involved in 5%, 5%, and 3% of the treatment discontinuations, respectively, and there was no difference observed by sex. In a post hoc analysis that examined detailed etiologies of AETD among the 176 subjects with constitutional or other symptoms, 68 (39%) included fever, fatigue, weight loss, or gastrointestinal symptoms; 42 (24%) neurologic or psychiatric side effects, and 15 (9%) elevations in hepatic transaminases or lactic acid. The type of AETD was similar between the 2 sexes.
Our finding that women on NNRTI regimens were more likely to discontinue HCV therapy than men is in agreement with other studies examining ARV regimen discontinuation in HIV infection. Women were more likely to discontinue efavirenz (EFV)-based regimens with 38.8% (95% CI: 28.8% to 48.7%) stopping EFV by 48 weeks of treatment compared with 28.3% of men (95% CI: 23.4% to 33.2%).23 In our analysis, among women with AETD, women receiving NNRTI-based regimens had more depression. This finding, along with the findings that women are more likely to have elevated plasma EFV concentrations24 are more likely to have mood disorders25 and may be more likely to experience depression while on interferon therapy,11 raise the possibility that neuropsychiatric side effects from interferon and EFV-based regimens may be accentuated in women. These findings should be interpreted with caution in this study, however, as we did not have data on type of NNRTI regimen and the number of women on NNRTI regimens who discontinued was small.
The finding that women were more likely to have AEDMs with AZT-containing regimens and a subgroup analysis demonstrating that the majority of AEDM on AZT-containing regimens were hematologic are not unexpected. Women are at an increased risk of developing anemia during ribavirin therapy,10 and our study suggests that AZT may also play a role in hematologic toxicities in women receiving ribavirin. In hepatitis C monoinfection trials, Sulkowski et al10 found that the incidence of reaching a Hgb <10 g/dL was 4-fold higher in women, whereas an analysis of interferon alpha-2a trials also found that women were more likely to have anemia.26 One study demonstrated higher levels of AZT in women,27 suggesting a possible mechanism for the additive toxicity of ribavirin and AZT. Anderson et al found that women had significantly higher intracellular concentrations of AZT with a female to male ratio of 2:3. Interestingly, we did not find a statistically significant sex difference in the rates of anemia leading to treatment discontinuation; the respective rates were small among both men and women, suggesting that these AEs were well managed in this clinical trial setting.
We also found that older age was independently associated with the incidence of AETD and dose modification. This is supported by Sulkowski et al10 who also found that older age was associated with hemoglobin decrease in hepatitis C monoinfection studies. The authors speculated that older age may impact hematopoietic reserves in bone marrow, leading to more bone marrow suppression than in younger subjects.10"
Abstract
Background: In HIV/ hepatitis C virus (HCV) coinfection, adverse events (AEs) during HCV therapy account for 12%-39% of treatment discontinuations. It is unknown whether sex influences complications.
Methods: Meta-analysis to study the effect of sex and other predictors of AEs in 3 randomized trials, ACTG 5071, APRICOT, and ANRSHCO2-RIBAVIC of Interferon (IFN) and Pegylated IFN (PEG), both with and without Ribavirin, in HIV/HCV coinfection. Primary endpoints were AEs requiring treatment discontinuation (AETD) or first dose modification (AEDM). Multi-covariate stratified logistic regression was used to study predictors and assess interactions with sex.
Results: Twenty-one percent of 1376 subjects were women; 61% had undetectable HIV RNA; 14% were antiretroviral (ARV) therapy naive at entry; median CD4 was 485 cells per cubicmillimeter. Seventeen percent had an AETD and 50% AEDM; women had more AETD than men (24% vs. 16% P = 0.003) and AEDM (61% vs. 48% P < 0.0001). AETD and AEDM occurred earlier in women; but the types of AETD and AEDM were similar between sexes. Seventy-four percent of AETDs and 49% of AEDMs involved constitutional AEs; 18% of AETD depression; and 26% of AEDM neutropenia. We identified interactions with sex and body mass index (BMI) (P = 0.04, continuous) and nonnucleoside reverse transcriptase inhibitor (P = 0.03); more AETDs were seen in men with lower BMI (P = 0.01) and in women on nonnucleoside reverse transcriptase inhibitors (P = 0.009). More AEDMs were seen with PEG [odds ratio (OR) = 2.07]; older age (OR = 1.48 per 10 years); decreasing BMI (OR = 1.04 per kg/m2); HCV genotype 1, 4 (OR = 1.31); Ishak 5, 6 (OR = 1.42); decreasing Hgb (OR = 1.23 per g/dL); and decreasing absolute neutrophil count (1.04 per 500 cells/mm3). Interactions between sex and ARV-naive status (P = 0.001) and zidovudine (P = 0.001) were identified: There were more AEDMs in ARV-naive women (P = 0.06) and ARV-experienced men (P = 0.001) and higher AEDMs in women with zidovudine (P = 0.0002).
Conclusions: Although there was no difference in type of AE, AETD and AEDM were more frequent and occurred earlier in women. In women, ARV regimen may be an important predictor of AETDs during HCV therapy and should be explored as a predictor of AEs in HIV/HCV coinfection trials.
INTRODUCTION
HIV and hepatitis C virus (HCV) coinfection is common, with reported prevalences of 16%-33% in HIV-infected individuals in the United States.1,2 Liver-related mortality is the leading cause of death among HIV-infected persons in the United States in the highly active antiretroviral therapy era.3 When compared with HCV monoinfection, hepatitis C therapy is less effective in HIV- and HCV-coinfected individuals due, in part, to high rates of treatment discontinuation.4-6 In HCV infection without HIV, the percentage of discontinuations secondary to adverse events (AEs) or laboratory abnormalities ranged from 7% to 21%,7-9 whereas in HIV coinfection, treatment discontinuations occurred in 12%-39%.4-6 Understanding the role of factors such as sex and its relationship with the development of adverse drug reactions will be critical to improving treatment outcomes in HIV and HCV coinfection.
In HCV monoinfection, women are more likely to experience anemia with interferon and ribavirin therapy10 and may be more likely to develop depression.11-13 In HIV infection, studies with nucleoside analogue therapy suggested that women were more likely to require dose modifications, to develop severe symptoms, and to experience AEs related to didanosine.14,15 There is little known, however, about the sex differences in AEs during HCV therapy in HIV/HCV coinfection. Additionally, the relationship between female sex, AEs during therapy, and other factors potentially related to AEs such as body mass index (BMI) and antiretroviral (ARV) regimen have not been well described in HIV and HCV coinfection.
The aim of our study was to investigate whether female sex was associated with an increased incidence and/or more rapid onset of AEs requiring treatment modification or discontinuation. In addition, we examined whether factors such as ARV regimen and BMI were important in predicting AEs in women and men.
RESULTS
One thousand three hundred seventy-six subjects were included in the analysis, 288 (21%) of whom were women; 133 (10%), 860 (62%), and 383 (28%) subjects were from A5071, APRICOT, and ANRSHCO2-RIBAVIC, respectively. Subjects from A5071 were more likely to be non-white (52%), older (median age 45 years), overweight, or obese (57%) and have HCV genotype 1 or 4 (80%) than the subjects from APRICOT (21%, 39 years, 39% and 68%) or from ANRSHCO2-RIBAVIC (5%, 39 years, 18% and 61%).
Overall, 67% of subjects were infected with HCV genotype 1 or 4, and 83% had Ishak fibrosis score <4 (Table 1). Treatment regimens included pegylated interferon and ribavirin in 40%, interferon and ribavirin in 39%, and pegylated interferon alone in 21%; 40% of men and 40% of women received pegylated interferon and ribavirin therapy. Seventeen percent of women and 13% of men were ARV naive (P = 0.16); 48% of women and 42% of men were on D4T-containing regimens (P = 0.11); 18% of women and 11% of men were on nucleoside reverse transcriptase inhibitor-only regimens (P = 0.004); 29% of women and 34% of men were on AZT-containing regimens (P = 0.15); and 26% of women and 28% of men were on NNRTI-containing regimens (P = 0.47).
Fifty-three percent of women vs. 67% of men completed study treatment as specified by the respective study protocol; 24% vs. 16% discontinued treatment early due to toxicities, 11% vs. 9% due to nonresponse, 9% vs. 6% due to other known reasons; 1 woman of 288 vs. 1 man of 1088 died, and 3% of both women and men were lost to follow-up (P = 0.002, stratified by study) (not shown in Table 1).
Adverse Events Requiring Treatment Discontinuation
Women were more likely to experience an AETD than men, 24% vs. 16% (P = 0.003). Primary etiologies of AETD among the 238 who experienced an AETD included constitutional or other symptoms in 176 (74%) and depression in 44 (18%). Discontinuation due to hematologic abnormalities was not common; anemia, thrombocytopenia, and neutropenia were involved in 5%, 5%, and 3% of the treatment discontinuations, respectively, and there was no difference observed by sex. In a post hoc analysis that examined detailed etiologies of AETD among the 176 subjects with constitutional or other symptoms, 68 (39%) included fever, fatigue, weight loss, or gastrointestinal symptoms; 42 (24%) neurologic or psychiatric side effects, and 15 (9%) elevations in hepatic transaminases or lactic acid. The type of AETD was similar between the 2 sexes.
Predictors of AETD
In simple stratified analysis, female sex [odds ratio (OR) = 1.63] was a predictor of AETD. In addition, older age and lower baseline hemoglobin were statistically significant and lower baseline BMI was a marginally significant risk factor of AETD (Table 2). There was no evidence of association between AETD and the other factors listed in Methods-Statistical Analysis. In multicovariate analysis, age (P < 0.0001) and interactions between sex and BMI (P = 0.04) and between sex and NNRTI (P = 0.03) were statistically significant (Table 2). Men with higher BMIs were less likely to experience AETD than men with lower BMIs (OR = 0.94). This association was not observed in women. Women on NNRTI-containing regimens were more likely to have an AETD than ARV-naive women or women on other ARV regimens (OR = 2.23), whereas in men, no association between NNRTI-containing regimen and AETD was observed. Of the 69 women with an AETD, depression was responsible for 16 of 69 AETDs (23%); women on NNRTI therapy were more likely to experience depression, 8 of 25 (32%) than those who were on other ARV or not on ARV 8 of 44 (18%); (P = 0.02).
Adverse Events Requiring Treatment Modification
Women were more likely to experience an AEDM than men, 61% vs. 48% (P < 0.0001). Neutropenia and anemia were the primary hematologic etiologies of AEDM, involved in 26% and 17% of the AEDMs, respectively, and 49% of AEDMs involved constitutional AEs, but the type of AEDM was similar in men and women. An analysis that examined only subjects who received pegylated interferon and ribavirin, the standard of care regimen, demonstrated similar results (not shown).
Predictors of AEDM
In simple stratified analysis, female sex was a predictor of AEDM (OR = 1.72). In addition, pegylated interferon-containing regimen; non-white race; older age; lower baseline BMI; HCV genotype 1 or 4; Ishak fibrosis score 5 or 6; CD4 cell count <500; ARV experienced; AZT use; and lower baseline ANC, Hgb, and alanine aminotransferase were statistically significant predictors of AEDM (Table 3). The other factors listed in the Methods-Statistical Analysis were not statistically significantly associated with AEDM. In multicovariate analysis, receipt of pegylated interferon therapy (OR = 2.07, P < 0.0001), increasing age (OR = 1.48 per 10 years), decreasing BMI (OR = 1.04 per kg/m2), HCV genotype 1, 4 (OR = 1.31), Ishak 5, 6 (OR = 1.42), decreasing ANC (OR = 1.04 per 500 cells/mm3), and decreasing Hgb (OR = 1.23 per g/dL) remained statistically significant (Table 3).
We also identified interactions between sex and ARV-naive status (P = 0.001) and between sex and AZT use (P = 0.001). Interestingly, ARV-naive women were more likely to experience AEDMs than ARV-experienced women (OR = 1.96, P = 0.06), but ARV-naive men were less likely to experience AEDMs (OR = 0.51, P = 0.001). In women, more AEDMs were seen with AZT compared with non-AZT regimens or no ARV (OR 3.56, P = 0.0002); but this association was not seen in men (P = 0.59). In a subgroup analysis examining etiologies of dose modifications in 175 women with AEDM, women on AZT-containing therapy were more likely to experience neutropenia and anemia: 20 of 67 (30%) vs. 21 of 108 (19%) (P = 0.12) and 23 of 67 (34%) vs. 13 of 108 (12%) (P = 0.0004), respectively.
Time to AETD and AEDM
Women discontinued therapy and required dose modification earlier than men. The Cox proportional hazards ratio for time to AETD was 1.54 (95% CI: 1.16 to 2.04) for women compared with men (P = 0.003), whereas the Cox proportional hazards ratio for time to AEDM was 1.43 (95% CI: 1.20 to 1.70) for women compared with men (P < 0.0001) (Fig. 1). The median time to AEDM was 24 weeks in women and 48 weeks in men. There was also a trend toward more rapid platelet decline in women; the median time to the lowest platelet level was 15.6 (12.1-18.1) vs. 18.1 (16.1-18.9) weeks (P = 0.05).
DISCUSSION
In a meta-analysis of 3 large HIV/HCV coinfection trials, women were more likely to experience an AETD or AEDM during HCV therapy in HIV infection. However, the observed types of AEs were similar between sexes. Additionally, AETD and AEDM occurred earlier in women. When exploring the effect modification by sex, women on regimens containing an NNRTI without a PI experienced more AETD and women on AZT-containing regimens experienced more AEs requiring interferon or ribavirin dose modification.
This is the first study to demonstrate that HIV-infected women on hepatitis C therapy experience more AETDs. Although similar sex effects on treatment discontinuation were not reported in large trials of HIV-uninfected HCV-infected women receiving interferon and ribavirin therapy,7-9 other hepatitis C monoinfection analyses have demonstrated that women experience some AEs (depression and anemia) more commonly than men.10,11 The relatively lower proportion of women enrolled in the landmark registration trials7-9 may have precluded analysis of sex effects and discontinuation rates.
When examining the HIV literature, our findings of higher treatment discontinuations in women are similar to some17,18 but not all14,19,20 studies in HIV infection. In the CASCADE collaboration, women were more likely to discontinue ARV therapy (HR = 1.61, 95% CI: 1.15 to 2.27),17 whereas in the ICONA study group, women were twice as likely to discontinue treatment secondary to toxicity.18 Conversely, 3 other studies did not find higher overall rates of treatment discontinuations among women.14,19,20
A sex effect on ARV modifications has also been noted in HIV studies; Currier et al14 demonstrated that women were 1.25 times more likely to modify didanosine dosage. In HIV infection, women are also more likely to experience AEs while on therapy with descriptions of increased rates of rash and hepatitis with nevirapine21 and lactic acidosis with nucleoside analogues.22 The reasons for heightened rates of AEs in women are poorly understood. Differences in body weight and composition, renal clearance, cellular kinase activity, and P-glycoprotein activity may all play a role.
Our finding that women on NNRTI regimens were more likely to discontinue HCV therapy than men is in agreement with other studies examining ARV regimen discontinuation in HIV infection. Women were more likely to discontinue efavirenz (EFV)-based regimens with 38.8% (95% CI: 28.8% to 48.7%) stopping EFV by 48 weeks of treatment compared with 28.3% of men (95% CI: 23.4% to 33.2%).23 In our analysis, among women with AETD, women receiving NNRTI-based regimens had more depression. This finding, along with the findings that women are more likely to have elevated plasma EFV concentrations24 are more likely to have mood disorders25 and may be more likely to experience depression while on interferon therapy,11 raise the possibility that neuropsychiatric side effects from interferon and EFV-based regimens may be accentuated in women. These findings should be interpreted with caution in this study, however, as we did not have data on type of NNRTI regimen and the number of women on NNRTI regimens who discontinued was small.
The finding that women were more likely to have AEDMs with AZT-containing regimens and a subgroup analysis demonstrating that the majority of AEDM on AZT-containing regimens were hematologic are not unexpected. Women are at an increased risk of developing anemia during ribavirin therapy,10 and our study suggests that AZT may also play a role in hematologic toxicities in women receiving ribavirin. In hepatitis C monoinfection trials, Sulkowski et al10 found that the incidence of reaching a Hgb <10 g/dL was 4-fold higher in women, whereas an analysis of interferon alpha-2a trials also found that women were more likely to have anemia.26 One study demonstrated higher levels of AZT in women,27 suggesting a possible mechanism for the additive toxicity of ribavirin and AZT. Anderson et al found that women had significantly higher intracellular concentrations of AZT with a female to male ratio of 2:3. Interestingly, we did not find a statistically significant sex difference in the rates of anemia leading to treatment discontinuation; the respective rates were small among both men and women, suggesting that these AEs were well managed in this clinical trial setting.
We also found that older age was independently associated with the incidence of AETD and dose modification. This is supported by Sulkowski et al10 who also found that older age was associated with hemoglobin decrease in hepatitis C monoinfection studies. The authors speculated that older age may impact hematopoietic reserves in bone marrow, leading to more bone marrow suppression than in younger subjects.10
One limitation of our analysis was the heterogeneity of treatment protocols. In ACTG 5071, ribavirin was dose escalated from 600 to 800 mg, and subjects who experienced severe AEs stopped therapy. This dose escalation, however, would only have masked severe AEs. Additionally, the 3 protocols included varying regimens of interferon and ribavirin, with 40% of individuals receiving combination therapy with pegylated interferon and ribavirin. Subgroup analyses on this group with combination therapy, however, demonstrated similar results to that of all regimens. Another limitation of the study included the extensive use of ARVs (AZT and stavudine) that are less common in clinical practice today. Newer more tolerable ARV regimens such as the nuclesos(t)ide transcriptase inhibitor combinations (ie, tenofovir/emtricitabine and abacavir/lamivudine), boosted atazanavir, and raltegravir may lead to a reduced rate of adverse reactions attributable to concomitant ARV and HCV therapy. Analyses of these newer regimens with hepatitis C therapy, and their interactions with sex, are needed. We also acknowledge the presence of competing risks such as LFU, death, nonresponse, and unknown reasons for discontinuation. Therefore, time to AETD and time to first dose modification, respectively, were also analyzed in the competing risks setting, treating death, nonresponse, LFU, and other known reason for treatment discontinuation as competing risks. The results were very similar to the results from Kaplan-Meier and Cox proportional hazards model, and the conclusions on the effect of sex were the same in both analyses. Competing risks may have also reduced the observed AEs and, if dropout secondary to competing risks was associated with covariates, then confounding may have been introduced. Finally, the overall numbers of women experiencing AETDs and AEDMs were low at 69 and 175, respectively, leading us to interpret the interactions and subgroup analyses, including comparisons of types of AEs between men and women, with caution.
In conclusion, women are more likely to experience AEs, leading to hepatitis C treatment dose modification and discontinuation in the setting of HIV/HCV coinfection. Women on NNRTI regimens were more likely to discontinue therapy, and women on AZT-containing regimens were more likely to require dose modifications, suggesting an important sex-mediated role of ARV regimen on the impact of AEs during hepatitis C therapy. ARV regimen may be an important predictor of treatment discontinuation and modification in women and should be further explored as predictors of AEs in HIV/HCV coinfection trials.
METHODS
We performed a meta-analysis of the AIDS Clinical Trials Group (ACTG) A5071, AIDS Pegasys Ribavirin International Coinfection Trial (APRICOT), and Agence Nationale de Recherches sur le SIDA (ANRS) HCO2-RIBAVIC HCV treatment studies in HIV/HCV coinfection, conducted by different clinical trial networks between 2000 and 2003. Subject-level data were obtained for each study. Only subjects who initiated HCV treatment were included in the analysis. Detailed inclusion criteria, study design, and criteria for treatment discontinuation and dose modifications are described in detail elsewhere.4-6 In A5071, subjects were randomized to receive 180 µg of peginterferon alfa-2a weekly for 48 weeks and dose-escalated ribavirin or 6 million IU of interferon alfa-2a 3 times weekly for 12 weeks followed by 3 million IU 3 times weekly for 36 weeks with dose-escalated ribavirin.5 Ribavirin was administered as 600 milligrams per day for 4 weeks, 800 milligrams per day for 4 weeks, and then 1000 milligrams per day for the remainder of the study. In APRICOT, subjects were randomized to peginterferon alfa-2a (180 µg/wk) plus ribavirin (800 mg/d), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU 3 times a week) plus ribavirin (800 mg/d).6 In RIBAVIC, subjects were randomized to 1.5 µg/kg peginterferon alfa-2b once a week or subcutaneous injections of 3 million units of interferon alfa-2b 3 times a week for 48 weeks. All subjects also received 800 mg of ribavirin daily.4 Laboratory toxicities, signs and symptoms, and clinical events, excluding death, were considered AEs. The primary endpoints were adverse events requiring treatment discontinuation (AETD) or first dose modification (AEDM). The primary endpoints were decided a priori and were selected because identification of factors responsible for treatment discontinuations and drug dose modifications may lead to implications for patient selection and management before and during therapy. Because the present analyses used data on subject level, the overall results are weighted by study, giving the greatest weight to APRICOT (62% of the N = 1376 subjects) followed by ANRSHCO2-RIBAVIC (28%) and A5071 (10%).
Statistical Analysis
Breslow-Day tests were used to ensure that it was appropriate to combine estimates from the 3 studies. Cochran-Mantel-Haenszel tests stratified by study were used to test statistical significance of differences in categorical variables between 2 groups. Stratified Wilcoxon rank-sum tests were used to test the statistical significance of differences between 2 groups in continuous variables. Predictors of AETD and AEDM were examined using simple logistic regression models, stratified by study. In addition to sex, predictors considered in analysis were HCV treatment (pegylated interferon-containing vs. not); race (white vs. non-white); age (continuous); BMI (continuous); HCV genotype (1, 4 vs. other); baseline Ishak fibrosis score (1-4 vs. higher); baseline HCV RNA (<800,000 vs. ≥800,000 IU/mL); baseline HIV-1 RNA (detectable vs. undetectable per definition of each study); baseline CD4 cell count (<500 vs. ≥500 cells/mm3); ARV naive at baseline; stavudine use at baseline; zidovudine (AZT) use at baseline; ARV regimen at baseline, nucleoside reverse transcriptase inhibitors only; containing nonnucleoside reverse transcriptase inhibitors (NNRTI) but no protease inhibitor (PI); containing any PI; baseline absolute neutrophil count (ANC, continuous); baseline platelets (continuous); baseline hemoglobin (continuous); baseline alanine aminotransferase (continuous); and baseline aspartate aminotransferase (continuous). Variables and their interactions with sex that were significant at 0.2 significance level in simple stratified logistic regression were considered in multi-covariate logistic regression models, stratified by study.
Kaplan-Meier estimates were used to summarize time-to-event results. Log-rank tests stratified by study were used to compare times to event between men and women. Stratified Cox proportional hazards model were used to provide an estimate for the magnitude of sex effect. Because AETD and AEDM are competing risks, times to AETD and AEDM were also analyzed using the competing risk methods16 (treating death, nonresponse, loss to follow-up (LFU), and other known reason (primarily administrative) for treatment discontinuation as competing risks. The results were very similar to the results from Kaplan-Meier and Cox proportional hazards models, and the conclusions on the effect of sex were the same in both analyses. Therefore, the results of standard Kaplan-Meier analysis along with Cox proportional hazards model are provided for simpler interpretation. Results were considered statistically significant if P < 0.05 (2 sided).
Source
October 7, 2010
HIV Positive Muppet Moves To Nigeria's Sesame Street
The first HIV-positive Muppets character joined the existing cast of the "Takalani Sesame", shown here, the South African version of the popular childrens television show.
Reuters/CORBIS
By: Claire McCormack
Elmo, Big Bird and Oscar the Grouch have made some new West African friends who are ready to expand the Sesame Street family.
The Nigerian version of Sesame Street, the latest in a long line of region-specific shows, will be hosted by Kami, a female muppet who is HIV-positive, has golden hair and a zest for adventure; and Kobi, an energetic, furry, blue muppet whose mischievous escapades help others learn from his mistakes.
With a population of over 150 million, nearly half of which are under the age of 14, Sesame Square will address the major challenges facing the young African community today including AIDS, malaria, gender inequality,and religious differences, as well as many positive aspects of Nigerian life. In the case of Zobi, he has a characterized obsession with yams - a traditional food in the Nigerian diet.
"We have a very focused health and hygiene umbrella concept area that we're concentrating on," Naila Farouky, senior director of international projects at Sesame Workshop.
As long as Zobi's love of yams doesn't turn into a love of cookies, NewsFeed welcomes Sesame Streets extended family.
Source
High-Dosage Opioid Prescription Correlates With Depression, Increased Pain Sensitivity, and Hepatitis Diagnoses: Presented at AAFP
By Carole VanSickle Ellis
DENVER -- October 5, 2010 -- High doses of opioid medication over an extended period of time will increase patient pain sensitivity. It also indicates a set of patient characteristics (depression, hepatitis C) that can be used to predict prescription abuse, researchers reported here October 2 at the American Academy of Family Physicians (AAFP) 2010 Scientific Assembly.
Lead investigator Shannon Essler, a pre-med student at Southwestern University, Georgetown, Texas, and her fellow researchers recommended that clinicians recognise dosages of 50 mg/day or less in morphine equivalence, and reconsider prescribing opioids above 115 mg/day for chronic, non-cancer pain to minimise the risk of addiction and abuse.
The 213 patients in this study had had low back pain for 3 months or longer during 2008; they were followed up in 2009. Patients who were pregnant or had cancer were excluded from the study, leaving a subject group of 204.
The research team used medical records to compile causes for lower back pain, procedural treatment for pain, comorbidities, and body mass index (BMI), reported Essler. A survey on demographic characteristics and other patient characteristics -- including anxiety, depression, and substance abuse -- completed the process and enabled the group to divide the subjects into 3 sections: nonusers of opioid medications (n = 100), moderate users (<=115 mg morphine equivalent per day, n = 94), and high users (>115 mg per day, n = 10).
Seventy percent of the subject group was female, 40% were Hispanic, and 45% were white. The average age was 55 (range: 19-90 years). Half of the subjects used the medication to control back pain, with the average dose for moderate users being 35 mg per day.
When the 3 groups were compared, some distinct differences were apparent. Among the high users, 70% were being treated for depression, while moderate and nonusers being treated for depression measured 44.7% and 26%, respectively (P =.002). Additionally, 30% of the high users had been diagnosed with hepatitis C, with only 10.6% of moderate users and 4% of nonusers receiving this diagnosis (P =.010).
Essler noted that this study was limited by a relatively small sample of high-dose users, but added that the results were significant enough to allow the recommendation that clinicians "reconsider the appropriateness of any opioid prescribing above 115 mg/day for non-cancer pain."
Funding for this study was provided by the Texas Academy of Family Physicians, the South Texas Area Health Education Center, and the Dean's Office, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
[Presentation title: Characteristics of Patients Using Extreme Opioid Dosages in the Treatment of Chronic Low Back Pain. Abstract P052]
Source
DENVER -- October 5, 2010 -- High doses of opioid medication over an extended period of time will increase patient pain sensitivity. It also indicates a set of patient characteristics (depression, hepatitis C) that can be used to predict prescription abuse, researchers reported here October 2 at the American Academy of Family Physicians (AAFP) 2010 Scientific Assembly.
Lead investigator Shannon Essler, a pre-med student at Southwestern University, Georgetown, Texas, and her fellow researchers recommended that clinicians recognise dosages of 50 mg/day or less in morphine equivalence, and reconsider prescribing opioids above 115 mg/day for chronic, non-cancer pain to minimise the risk of addiction and abuse.
The 213 patients in this study had had low back pain for 3 months or longer during 2008; they were followed up in 2009. Patients who were pregnant or had cancer were excluded from the study, leaving a subject group of 204.
The research team used medical records to compile causes for lower back pain, procedural treatment for pain, comorbidities, and body mass index (BMI), reported Essler. A survey on demographic characteristics and other patient characteristics -- including anxiety, depression, and substance abuse -- completed the process and enabled the group to divide the subjects into 3 sections: nonusers of opioid medications (n = 100), moderate users (<=115 mg morphine equivalent per day, n = 94), and high users (>115 mg per day, n = 10).
Seventy percent of the subject group was female, 40% were Hispanic, and 45% were white. The average age was 55 (range: 19-90 years). Half of the subjects used the medication to control back pain, with the average dose for moderate users being 35 mg per day.
When the 3 groups were compared, some distinct differences were apparent. Among the high users, 70% were being treated for depression, while moderate and nonusers being treated for depression measured 44.7% and 26%, respectively (P =.002). Additionally, 30% of the high users had been diagnosed with hepatitis C, with only 10.6% of moderate users and 4% of nonusers receiving this diagnosis (P =.010).
Essler noted that this study was limited by a relatively small sample of high-dose users, but added that the results were significant enough to allow the recommendation that clinicians "reconsider the appropriateness of any opioid prescribing above 115 mg/day for non-cancer pain."
Funding for this study was provided by the Texas Academy of Family Physicians, the South Texas Area Health Education Center, and the Dean's Office, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
[Presentation title: Characteristics of Patients Using Extreme Opioid Dosages in the Treatment of Chronic Low Back Pain. Abstract P052]
Source
Diabetes Enhances Hepatocarcinogenesis in Noncirrhotic, Interferon-treated Hepatitis C Patients
American Journal of Medicine
Volume 123, Issue 10, Pages 951-956.e1 (October 2010)
Yusuke Kawamura, MD, Yasuji Arase, MD, Kenji Ikeda, MD, Miharu Hirakawa, MD, Tetsuya Hosaka, MD, Masahiro Kobayashi, MD, Satoshi Saitoh, MD, Hiromi Yatsuji, MD, Hitomi Sezaki, MD, Norio Akuta, MD, Fumitaka Suzuki, MD, Yoshiyuki Suzuki, MD, Hiromitsu Kumada, MD
Abstract
Background
This retrospective cohort study assessed the impact of diabetes mellitus on hepatocarcinogenesis and determined the predictors of hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus infection.
Methods
A total of 2058 hepatitis C virus-positive, noncirrhotic patients treated with interferon were enrolled. The median follow-up period was 6.7 years. The primary end point was the onset of hepatocellular carcinoma. The cumulative rate of new hepatocellular carcinoma cases was computed by the Kaplan–Meier method and Cox proportional hazard analysis according to diabetic state and response to interferon therapy.
Results
The cumulative rates of hepatocellular carcinoma in diabetic patients (3.2% at 4 years, 8.5% at 8 years, and 24.4% at 12 years) were significantly higher than those of nondiabetic patients (1.3% at 4 years, 2.2% at 8 years, and 5.6% at 12 years, P<.001). In patients with a sustained virologic response, diabetes had no significant effect on the rate of hepatocarcinogenesis. In contrast, the rate in patients with a nonsustained virologic response was significantly higher in diabetic than in nondiabetic patients. Multivariate analysis identified lack of sustained virologic response (hazard ratio [HR] 7.28; 95% confidence interval [CI], 3.28-16.15; P<.001) and diabetes as independent risk factors for hepatocarcinogenesis (HR 2.00; 95% CI, 1.05-3.84; P=.036).
Conclusions
Our results highlight the enhancing effect of diabetes mellitus on hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus. The sustained virologic response induced by interferon therapy eliminates the influence of diabetes and markedly reduces the rate of hepatocarcinogenesis in such patients.
Keywords: Diabetes, Hepatocellular carcinoma, Interferon, Sustained virologic response
Department of Hepatology, Toranomon Hospital, Tokyo, Japan
Requests for reprints should be addressed to Yusuke Kawamura, MD, Department of Hepatology, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan
Funding: Okinaka Memorial Institute for Medical Research and Japanese Ministry of Health, Labour and Welfare.
Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.
Authorship: All authors had access to the data and played a role in writing this manuscript.
PII: S0002-9343(10)00468-7
doi:10.1016/j.amjmed.2010.05.013
© 2010 Elsevier Inc. All rights reserved
Source
Volume 123, Issue 10, Pages 951-956.e1 (October 2010)
Yusuke Kawamura, MD, Yasuji Arase, MD, Kenji Ikeda, MD, Miharu Hirakawa, MD, Tetsuya Hosaka, MD, Masahiro Kobayashi, MD, Satoshi Saitoh, MD, Hiromi Yatsuji, MD, Hitomi Sezaki, MD, Norio Akuta, MD, Fumitaka Suzuki, MD, Yoshiyuki Suzuki, MD, Hiromitsu Kumada, MD
Abstract
Background
This retrospective cohort study assessed the impact of diabetes mellitus on hepatocarcinogenesis and determined the predictors of hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus infection.
Methods
A total of 2058 hepatitis C virus-positive, noncirrhotic patients treated with interferon were enrolled. The median follow-up period was 6.7 years. The primary end point was the onset of hepatocellular carcinoma. The cumulative rate of new hepatocellular carcinoma cases was computed by the Kaplan–Meier method and Cox proportional hazard analysis according to diabetic state and response to interferon therapy.
Results
The cumulative rates of hepatocellular carcinoma in diabetic patients (3.2% at 4 years, 8.5% at 8 years, and 24.4% at 12 years) were significantly higher than those of nondiabetic patients (1.3% at 4 years, 2.2% at 8 years, and 5.6% at 12 years, P<.001). In patients with a sustained virologic response, diabetes had no significant effect on the rate of hepatocarcinogenesis. In contrast, the rate in patients with a nonsustained virologic response was significantly higher in diabetic than in nondiabetic patients. Multivariate analysis identified lack of sustained virologic response (hazard ratio [HR] 7.28; 95% confidence interval [CI], 3.28-16.15; P<.001) and diabetes as independent risk factors for hepatocarcinogenesis (HR 2.00; 95% CI, 1.05-3.84; P=.036).
Conclusions
Our results highlight the enhancing effect of diabetes mellitus on hepatocarcinogenesis in noncirrhotic, interferon-treated patients with hepatitis C virus. The sustained virologic response induced by interferon therapy eliminates the influence of diabetes and markedly reduces the rate of hepatocarcinogenesis in such patients.
Keywords: Diabetes, Hepatocellular carcinoma, Interferon, Sustained virologic response
Department of Hepatology, Toranomon Hospital, Tokyo, Japan
Requests for reprints should be addressed to Yusuke Kawamura, MD, Department of Hepatology, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan
Funding: Okinaka Memorial Institute for Medical Research and Japanese Ministry of Health, Labour and Welfare.
Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript.
Authorship: All authors had access to the data and played a role in writing this manuscript.
PII: S0002-9343(10)00468-7
doi:10.1016/j.amjmed.2010.05.013
© 2010 Elsevier Inc. All rights reserved
Source
Barriers to accessing care in patients with chronic hepatitis C: the impact of depression
D. M. Evon 1, K. M. Simpson 1, D. Esserman 2,3, A. Verma 1, S. Smith 4, M. W. Fried 1
Article first published online: 17 SEP 2010
DOI: 10.1111/j.1365-2036.2010.04460.x
Aliment Pharmacol Ther 2010; 32: 1163–1173
Summary
Background Patients with hepatitis C viral (HCV) may perceive barriers to accessing speciality care for HCV, and these barriers may be related to depressive symptoms.
Aim To evaluate the relationship between barriers to care, demographics, and depressive symptoms.
Methods A cross-sectional analysis of 126 patients referred for HCV at two speciality HCV clinics. Barriers to care, depressive symptoms and sociodemographics were measured using standardized instruments. A retrospective chart review was conducted to collect clinical outcome data.
Results Depressive symptoms were reported in 26%. Common barriers included lack of personal financial resources; lack of HCV knowledge in the community; lack of professionals competent in HCV care; stigmatization of HCV; and long distances to clinics offering care. After we controlled for sociodemographics, depression accounted for an additional 7–18% of variability in all barriers (all p values <0.01). Lower depression, marital and employment status were associated with subsequent receipt of HCV treatment in 38% (45/120) of patients; perceived barriers were not.
Conclusions Depression is independently associated with perceived barriers to care. Higher depressive scores, but not perceived barriers, were associated with nontreatment. Healthcare providers who diagnose HCV need to be cognizant of numerous perceived barriers to accessing HCV care, and the impact that depression may have on these perceptions and receipt of treatment.
Source
Article first published online: 17 SEP 2010
DOI: 10.1111/j.1365-2036.2010.04460.x
Aliment Pharmacol Ther 2010; 32: 1163–1173
Summary
Background Patients with hepatitis C viral (HCV) may perceive barriers to accessing speciality care for HCV, and these barriers may be related to depressive symptoms.
Aim To evaluate the relationship between barriers to care, demographics, and depressive symptoms.
Methods A cross-sectional analysis of 126 patients referred for HCV at two speciality HCV clinics. Barriers to care, depressive symptoms and sociodemographics were measured using standardized instruments. A retrospective chart review was conducted to collect clinical outcome data.
Results Depressive symptoms were reported in 26%. Common barriers included lack of personal financial resources; lack of HCV knowledge in the community; lack of professionals competent in HCV care; stigmatization of HCV; and long distances to clinics offering care. After we controlled for sociodemographics, depression accounted for an additional 7–18% of variability in all barriers (all p values <0.01). Lower depression, marital and employment status were associated with subsequent receipt of HCV treatment in 38% (45/120) of patients; perceived barriers were not.
Conclusions Depression is independently associated with perceived barriers to care. Higher depressive scores, but not perceived barriers, were associated with nontreatment. Healthcare providers who diagnose HCV need to be cognizant of numerous perceived barriers to accessing HCV care, and the impact that depression may have on these perceptions and receipt of treatment.
Source
The skinny on fatty liver: Weight and metabolic disorders put millions at risk
By Katie Charles
THE DAILY CHECKUP
Wednesday, October 6th 2010, 4:00 AM
Who's at risk
About 30% of Americans have fatty liver, a condition whose name says it all. "Fatty liver is a condition where there's excess fat accumulation in the liver," says Chang. "A subset of patients who have fat in their liver have fat plus additional damage, which we call nonalcoholic steatohepatitis (NASH)."
If left unmanaged, NASH can lead to cirrhosis, liver transplant or liver cancer. "A liver biopsy is the only way to tell whether someone with fatty liver has the more severe NASH, although sometimes we can make an estimation without having to perform a liver biopsy," says Chang.
Doctors estimate that 2% to 9% of Americans have NASH. "Fatty liver disease is now a common cause of liver abnormalities and the most common cause of abnormal liver tests in the United States," says Chang. "We're seeing more patients for transplant or cancer with the fatty liver disease as the underlying cause."
At this point, fatty liver disease is even more prevalent than hepatitis C, which affects 1.5% of the population.
The main risk factors for fatty liver are obesity and metabolic syndrome. "Fatty liver is the liver manifestation of metabolic syndrome," says Chang. "So it's associated with all the other features of metabolic syndrome: high blood pressure, diabetes, high cholesterol and an increased waistline."
A minority of patients with fatty liver don't have metabolic syndrome. "Some medications can cause fatty liver, and there are genetically inherited disorders of fat metabolism, including a rare condition called congenital lipodystrophy that can be associated with fatty liver," says Chang.
The cause of fatty liver disease is still unclear and is an area of active research. Fatty liver is a condition that increases with age, although young people and kids can be affected. "The prevalence increases with age for a few reasons," says Chang. "Some of it is weight gain over time, and some of it is that the longer you've had fat in the liver, the more years you've had to develop liver damage."
Signs and symptoms
Fatty liver is often a stealth disease. "The early signs and symptoms are often silent," says Chang.
"It's usually an incidental diagnosis picked up by having blood drawn as part of a routine check-up." Most primary-care physicians run liver tests as part of a yearly physical, but it's worth asking to make sure your doctor tests for fatty liver.
Liver damage only begins to show symptoms when it reaches the point of end-stage liver disease. "At this point, the patient progresses to cirrhosis, which can cause symptoms a patient could note on his own — things like fluid retention and jaundice," says Chang.
"Another big concern or end-stage complication is liver cancer," she says. As more patients develop fatty liver disease, doctors are seeing increased amounts of liver cancer that developed in the presence of fatty liver disease. "The goal is to prevent fatty liver from progressing to cirrhosis," says Chang. "Or better yet, preventing it in the first place."
Traditional treatment
The first step for patients diagnosed with fatty liver is to develop a plan with their primary care physician to address obesity and related issues like diabetes and cholesterol. "Losing weight and keeping diabetes under control can improve fatty liver or keep it from causing damage," says Chang.
"I advise patients to limit both saturated fat and high-fructose-containing food products like sodas, both of which are associated with obesity," she says.
About a third of patients who have fatty liver get better, one third stay the same and one third get worse. The focus is on prevention and containment, because doctors don't have many options for patients whose disease worsens to the point of nonalcoholic steatohepatitis (NASH).
"Right now we have no FDA-approved medications to treat NASH," says Chang. "While there has been research using diabetes drugs, weight-loss medications and cholesterol medications to treat NASH, there is not enough evidence at this time to show that these drugs can be used to treat NASH directly."
Patients whose disease continues to progress can develop cirrhosis, an outcome doctors work very hard to prevent. "Once there is cirrhosis in a patient with NASH, there aren't a lot of options to reverse the damage," says Chang.
"Short of a liver transplant, there isn't much we can do besides advise to lose weight and keep diabetes and cholesterol under control," she says. Even liver transplant isn't a perfect cure, because the disease can come back after a transplant.
Research breakthroughs
One recent study had promising results for using vitamin E to fight fatty liver. "Last year, a National Institutes of Health multi-site collaboration called the PIVENS trial published its findings that using vitamin E improved liver tests and reversed scarring in the livers of patients with NASH," says Chang. "We need more supporting studies, but it's worth asking your doctor if vitamin E could help."
Questions for your doctor
Because this disease is usually asymptomatic, it's all the more important for patients to ask, "Could I have fatty liver disease?"
If you've been diagnosed, then the question becomes, "What can I do to keep my fatty liver from progressing?"
Eating a healthy diet and exercising regularly can go a long way toward keep fatty liver disease under control.
Source
THE DAILY CHECKUP
Wednesday, October 6th 2010, 4:00 AM
Who's at risk
About 30% of Americans have fatty liver, a condition whose name says it all. "Fatty liver is a condition where there's excess fat accumulation in the liver," says Chang. "A subset of patients who have fat in their liver have fat plus additional damage, which we call nonalcoholic steatohepatitis (NASH)."
If left unmanaged, NASH can lead to cirrhosis, liver transplant or liver cancer. "A liver biopsy is the only way to tell whether someone with fatty liver has the more severe NASH, although sometimes we can make an estimation without having to perform a liver biopsy," says Chang.
Doctors estimate that 2% to 9% of Americans have NASH. "Fatty liver disease is now a common cause of liver abnormalities and the most common cause of abnormal liver tests in the United States," says Chang. "We're seeing more patients for transplant or cancer with the fatty liver disease as the underlying cause."
At this point, fatty liver disease is even more prevalent than hepatitis C, which affects 1.5% of the population.
The main risk factors for fatty liver are obesity and metabolic syndrome. "Fatty liver is the liver manifestation of metabolic syndrome," says Chang. "So it's associated with all the other features of metabolic syndrome: high blood pressure, diabetes, high cholesterol and an increased waistline."
A minority of patients with fatty liver don't have metabolic syndrome. "Some medications can cause fatty liver, and there are genetically inherited disorders of fat metabolism, including a rare condition called congenital lipodystrophy that can be associated with fatty liver," says Chang.
The cause of fatty liver disease is still unclear and is an area of active research. Fatty liver is a condition that increases with age, although young people and kids can be affected. "The prevalence increases with age for a few reasons," says Chang. "Some of it is weight gain over time, and some of it is that the longer you've had fat in the liver, the more years you've had to develop liver damage."
Signs and symptoms
Fatty liver is often a stealth disease. "The early signs and symptoms are often silent," says Chang.
"It's usually an incidental diagnosis picked up by having blood drawn as part of a routine check-up." Most primary-care physicians run liver tests as part of a yearly physical, but it's worth asking to make sure your doctor tests for fatty liver.
Liver damage only begins to show symptoms when it reaches the point of end-stage liver disease. "At this point, the patient progresses to cirrhosis, which can cause symptoms a patient could note on his own — things like fluid retention and jaundice," says Chang.
"Another big concern or end-stage complication is liver cancer," she says. As more patients develop fatty liver disease, doctors are seeing increased amounts of liver cancer that developed in the presence of fatty liver disease. "The goal is to prevent fatty liver from progressing to cirrhosis," says Chang. "Or better yet, preventing it in the first place."
Traditional treatment
The first step for patients diagnosed with fatty liver is to develop a plan with their primary care physician to address obesity and related issues like diabetes and cholesterol. "Losing weight and keeping diabetes under control can improve fatty liver or keep it from causing damage," says Chang.
"I advise patients to limit both saturated fat and high-fructose-containing food products like sodas, both of which are associated with obesity," she says.
About a third of patients who have fatty liver get better, one third stay the same and one third get worse. The focus is on prevention and containment, because doctors don't have many options for patients whose disease worsens to the point of nonalcoholic steatohepatitis (NASH).
"Right now we have no FDA-approved medications to treat NASH," says Chang. "While there has been research using diabetes drugs, weight-loss medications and cholesterol medications to treat NASH, there is not enough evidence at this time to show that these drugs can be used to treat NASH directly."
Patients whose disease continues to progress can develop cirrhosis, an outcome doctors work very hard to prevent. "Once there is cirrhosis in a patient with NASH, there aren't a lot of options to reverse the damage," says Chang.
"Short of a liver transplant, there isn't much we can do besides advise to lose weight and keep diabetes and cholesterol under control," she says. Even liver transplant isn't a perfect cure, because the disease can come back after a transplant.
Research breakthroughs
One recent study had promising results for using vitamin E to fight fatty liver. "Last year, a National Institutes of Health multi-site collaboration called the PIVENS trial published its findings that using vitamin E improved liver tests and reversed scarring in the livers of patients with NASH," says Chang. "We need more supporting studies, but it's worth asking your doctor if vitamin E could help."
Questions for your doctor
Because this disease is usually asymptomatic, it's all the more important for patients to ask, "Could I have fatty liver disease?"
If you've been diagnosed, then the question becomes, "What can I do to keep my fatty liver from progressing?"
Eating a healthy diet and exercising regularly can go a long way toward keep fatty liver disease under control.
Source
A So-So HIV Vaccine May Be a Hard Sell
October 7, 2010
A collection of studies shows that any HIV vaccine, while highly sought by doctors to battle the epidemic, would only be requested by some.
By Brad Wittwer
An HIV vaccine — the dream of medical science for a quarter-century — isn’t all that far off. Given that 2.7 million new HIV infections in 2008 alone brought the world total to 33.4 million infected, there is a genuine need.
But rather than a line out the door the first day of availability, new research by Peter Newman and Carmen Logie of the University of Toronto suggests that an HIV vaccine will mostly cause hypochondriacs to rush to their local clinic and others to, at best, scribble an appointment in the weekly planner.
The team gathered 30 original studies, mostly from North America but also from Africa and Southeast Asia, to analyze HIV vaccine acceptability. Selecting 20 studies involving 7,576 participants between 1996 and 2010, the researchers ranked HIV “vaccine acceptability” — how in demand a vaccine would be — on a 100-point scale for each study. Results ranged from 37.2 to 94.0, with the average being 65.3.
Not surprisingly, results varied depending on how effective the putative vaccine would be. Limiting the testing to 11 studies, acceptability was 73.8 for a high-efficacy vaccine (80-95 percent) versus 40.4 for a moderate-efficacy vaccine (50 percent).
The results “raise cause for concern given the likelihood that initial HIV vaccines may be of low to moderate efficacy,” the authors write.
Across studies, acceptance rose alongside vaccination efficacy, duration of protection and perception of being at risk and fell with concerns over side effects, cost, pragmatic obstacles, safety concerns, fear of vaccines and fear of needles. The perception that a vaccine would be very effective drastically increased expectations of use, while the idea that someone wasn’t in the “risk group” for HIV/AIDS infection significantly decreased use.
To overcome this wariness, the researchers propose educating people’s perceptions of susceptibility to be more accurate — most underestimate their current risk of infection by the virus but if educated, people would be more apt to request a vaccine as is warranted. They also propose subsidies to reduce costs — free transportation to clinics for example would be one.
The authors emphasize the need for more research, since roughly 75 percent of the studies were conducted in North America and not Africa, which has the highest rates of HIV infection. In different cultural and socio-economic settings, the factors that most affect vaccine acceptability may be altogether different. Cost and pragmatic factors like remote access will take on a new meaning in less-developed nations.
Source
A collection of studies shows that any HIV vaccine, while highly sought by doctors to battle the epidemic, would only be requested by some.
By Brad Wittwer
An HIV vaccine — the dream of medical science for a quarter-century — isn’t all that far off. Given that 2.7 million new HIV infections in 2008 alone brought the world total to 33.4 million infected, there is a genuine need.
But rather than a line out the door the first day of availability, new research by Peter Newman and Carmen Logie of the University of Toronto suggests that an HIV vaccine will mostly cause hypochondriacs to rush to their local clinic and others to, at best, scribble an appointment in the weekly planner.
The team gathered 30 original studies, mostly from North America but also from Africa and Southeast Asia, to analyze HIV vaccine acceptability. Selecting 20 studies involving 7,576 participants between 1996 and 2010, the researchers ranked HIV “vaccine acceptability” — how in demand a vaccine would be — on a 100-point scale for each study. Results ranged from 37.2 to 94.0, with the average being 65.3.
Not surprisingly, results varied depending on how effective the putative vaccine would be. Limiting the testing to 11 studies, acceptability was 73.8 for a high-efficacy vaccine (80-95 percent) versus 40.4 for a moderate-efficacy vaccine (50 percent).
The results “raise cause for concern given the likelihood that initial HIV vaccines may be of low to moderate efficacy,” the authors write.
Across studies, acceptance rose alongside vaccination efficacy, duration of protection and perception of being at risk and fell with concerns over side effects, cost, pragmatic obstacles, safety concerns, fear of vaccines and fear of needles. The perception that a vaccine would be very effective drastically increased expectations of use, while the idea that someone wasn’t in the “risk group” for HIV/AIDS infection significantly decreased use.
To overcome this wariness, the researchers propose educating people’s perceptions of susceptibility to be more accurate — most underestimate their current risk of infection by the virus but if educated, people would be more apt to request a vaccine as is warranted. They also propose subsidies to reduce costs — free transportation to clinics for example would be one.
The authors emphasize the need for more research, since roughly 75 percent of the studies were conducted in North America and not Africa, which has the highest rates of HIV infection. In different cultural and socio-economic settings, the factors that most affect vaccine acceptability may be altogether different. Cost and pragmatic factors like remote access will take on a new meaning in less-developed nations.
Source
October 5, 2010
Hep C can infect, damage brain tissues: Report
By Sarah O'Donnell,
Edmonton Journal
October 5, 2010 9:05 PM
EDMONTON — A virus best known for the damage it does to the liver can also damage brain cells, University of Alberta researchers report in a new study.
The research into the impact of hepatitis C on the brain is significant, they say, because it marks the first time scientists have been able to show that the virus can infect the brain.
"It has been a question for a long time," said Pornpun Vivithanaporn, a post-doctoral fellow in the U of A's Faculty of Medicine and Dentistry and first author of the hepatitis C study, which was published last week in the Public Library of Science One Journal.
"It proves the virus has implications on neurological disease," she said Tuesday.
Hepatitis C infects about 170 million people globally and about 300,000 in Canada. It targets the liver, causing inflammation and cirrhosis.
Researchers already knew that severe liver disease can affect a person's brain, but more recent research suggested that hepatitis C patients without serious liver problems also could suffer from brain-related issues such as memory loss, trouble concentrating, apathy and depression.
The new study allowed a team of researchers to show precisely how the hepatitis C virus can infect brain cells on its own.
"That had never been shown before," said lead researcher Dr. Christopher Power, a neurologist who works in the U of A's Faculty of Medicine and Dentistry. "It gets in there, it infects and it replicates. For a virologist, that's a really core observation. You can see infection of the cells and you can see replication."
To show how the hepatitis C virus infects brain cells, Power pointed to a computer screen in his U of A lab on Tuesday.
On one side of the screen, pictures of two healthy brain cells appeared in red. On the other side, those same cells appeared peppered with green dots. And in this picture, green is bad since it represents a buildup of viral proteins that eventually damage and kill the cell. In a way, Power explained, the virus can cause brain cells to drown in their own garbage.
The discovery is important, Power said for a couple of reasons.
First, he said, there are immediate clinical implications. "It tells us we need to be vigilant for neurological problems for people who have hepatitis C," he said.
That would mean taking such steps as ensuring patients have assess to a neurologist or psychologist on their team of physicians as well as a liver specialist.
"The second issue is it underscores the importance (of) developing new treatment for hepatitis C so we can prevent infection of the brain," said Power, whose research is funded by Alberta Innovates — Health Solutions and the Canadian Institutes of Health Research.
There is now no vaccine to prevent hepatitis C. Researchers have uncovered some treatments that work for a portion of patients infected with hepatitis C, but those also can have serious side effects for some people.
Michael Harmsworth, a hepatitis C sufferer who counts Power among his five doctors, said Tuesday he was extremely interested to learn about the research team's discovery. He said he hadn't realized that hepatitis C had the potential to affect the brain until Power showed him computer images of infected tissue samples.
Harmsworth, who was diagnosed about 13 years ago, said it all points toward progress.
"It's making me think, 'Hey, I may still have my time left here,'" Harmsworth said. "My little girl is nine years old and I want to be here when she turns 16 and goes to the prom."
© Copyright (c) The Edmonton Journal
Source
Edmonton Journal
October 5, 2010 9:05 PM
EDMONTON — A virus best known for the damage it does to the liver can also damage brain cells, University of Alberta researchers report in a new study.
The research into the impact of hepatitis C on the brain is significant, they say, because it marks the first time scientists have been able to show that the virus can infect the brain.
"It has been a question for a long time," said Pornpun Vivithanaporn, a post-doctoral fellow in the U of A's Faculty of Medicine and Dentistry and first author of the hepatitis C study, which was published last week in the Public Library of Science One Journal.
"It proves the virus has implications on neurological disease," she said Tuesday.
Hepatitis C infects about 170 million people globally and about 300,000 in Canada. It targets the liver, causing inflammation and cirrhosis.
Researchers already knew that severe liver disease can affect a person's brain, but more recent research suggested that hepatitis C patients without serious liver problems also could suffer from brain-related issues such as memory loss, trouble concentrating, apathy and depression.
The new study allowed a team of researchers to show precisely how the hepatitis C virus can infect brain cells on its own.
"That had never been shown before," said lead researcher Dr. Christopher Power, a neurologist who works in the U of A's Faculty of Medicine and Dentistry. "It gets in there, it infects and it replicates. For a virologist, that's a really core observation. You can see infection of the cells and you can see replication."
To show how the hepatitis C virus infects brain cells, Power pointed to a computer screen in his U of A lab on Tuesday.
On one side of the screen, pictures of two healthy brain cells appeared in red. On the other side, those same cells appeared peppered with green dots. And in this picture, green is bad since it represents a buildup of viral proteins that eventually damage and kill the cell. In a way, Power explained, the virus can cause brain cells to drown in their own garbage.
The discovery is important, Power said for a couple of reasons.
First, he said, there are immediate clinical implications. "It tells us we need to be vigilant for neurological problems for people who have hepatitis C," he said.
That would mean taking such steps as ensuring patients have assess to a neurologist or psychologist on their team of physicians as well as a liver specialist.
"The second issue is it underscores the importance (of) developing new treatment for hepatitis C so we can prevent infection of the brain," said Power, whose research is funded by Alberta Innovates — Health Solutions and the Canadian Institutes of Health Research.
There is now no vaccine to prevent hepatitis C. Researchers have uncovered some treatments that work for a portion of patients infected with hepatitis C, but those also can have serious side effects for some people.
Michael Harmsworth, a hepatitis C sufferer who counts Power among his five doctors, said Tuesday he was extremely interested to learn about the research team's discovery. He said he hadn't realized that hepatitis C had the potential to affect the brain until Power showed him computer images of infected tissue samples.
Harmsworth, who was diagnosed about 13 years ago, said it all points toward progress.
"It's making me think, 'Hey, I may still have my time left here,'" Harmsworth said. "My little girl is nine years old and I want to be here when she turns 16 and goes to the prom."
© Copyright (c) The Edmonton Journal
Source
Obama Administration's Pledge to Global Fund to Fight HIV/AIDS, Malaria and Tuberculosis
Office of the Spokesman
Washington, DC
October 5, 2010
As part of America’s leadership in saving lives and alleviating suffering around the world, the United States announced today that it intends to make an unprecedented three-year pledge of support to the Global Fund to Fight AIDS, Tuberculosis and Malaria. The pledge is tied to the call for smart investments and shared responsibility to reach the goal of saving more lives efficiently and effectively.
The Obama Administration intends to seek $4 billion for the Fund for 2011 through 2013 to continue America’s strong support for this important multilateral partner. This pledge is a 38% increase in the U.S. investment over the preceding three-year period – a substantial increase especially in light of the overall budget challenges and the largest increase by far of any donor nation this year.
This historic pledge has three goals:
Washington, DC
October 5, 2010
As part of America’s leadership in saving lives and alleviating suffering around the world, the United States announced today that it intends to make an unprecedented three-year pledge of support to the Global Fund to Fight AIDS, Tuberculosis and Malaria. The pledge is tied to the call for smart investments and shared responsibility to reach the goal of saving more lives efficiently and effectively.
The Obama Administration intends to seek $4 billion for the Fund for 2011 through 2013 to continue America’s strong support for this important multilateral partner. This pledge is a 38% increase in the U.S. investment over the preceding three-year period – a substantial increase especially in light of the overall budget challenges and the largest increase by far of any donor nation this year.
This historic pledge has three goals:
- To save more lives by driving needed reforms and ensuring smart, effective investments are being made: The Fund has demonstrated remarkable success over the past eight years in mobilizing and disbursing resources. We must build upon this success by driving needed reforms including better grants management; greater country-level collaboration to avoid duplication of efforts; closing gaps in services; reducing reporting burdens on host countries; better accountability for funds in grants to ensure proper use of scarce resources; and better monitoring and evaluation to ensure goals of grants are met. The U.S. calls upon the Global Fund Board to develop an action agenda in the near future that includes clear timelines and measures progress so all parties can be held accountable for clear action steps.
- To leverage other donor nations’ contributions in order to save more lives; increase life expectancies; and alleviate suffering: This commitment serves as a challenge to other donors. If other donors scale up their commitments at a similar rate, the Global Fund is expected to be able to proceed with new rounds of grants while continuing existing grants during 2011-2013.
- To continue to demonstrate U.S. leadership in the ultimate measurement of success – increasing the number of lives saved: The U.S. was the first and by far the largest contributor to the Fund, providing more than $5.1 billion to date. This pledge is part of a comprehensive approach to combating AIDS, TB, and malaria through President Obama’s Global Health Initiative (GHI), which supports coordinated interventions aimed at reducing lives lost from the three diseases and other health challenges.
With this U.S. commitment and scaled-up contributions from other donors, the Global Fund projects that it will be able to achieve the following results by 2015:
- A total of 4.4 million people on antiretroviral therapy, up from 2.5 million at the end of 2009
- 2.5 million orphans and vulnerable children provided with support annually, up from 1.4 million in 2009
- 610,000 HIV-positive pregnant women receiving prevention of mother-to-child transmission services annually, compared to 345,000 in 2009
- 3.9 million tuberculosis treatment regimens provided annually, up from 1.4 million in 2009
- 110 million insecticide-treated bed nets for malaria prevention distributed annually, up from 34 million in 2009.
CDC's 'Winnable Battles' Out of Step with Healthcare Reform and Achieving Health Equity for the American People, Says Ted Fang, Co-Founder, Hep B Free
Ending Liver Cancer Is The Most Winnable Battle In American Healthcare Today
SAN FRANCISCO, Oct. 5 /PRNewswire/ -- In response to the Centers for Disease Control (CDC) Director Dr. Thomas Frieden's declaration of "six winnable battles" as healthcare priorities, Ted Fang, Director, AsianWeek Foundation and Co-Founder, Hep B Free movement, released the following statement:
"CDC's new prioritization of 'six winnable battles' once again demonstrates their poor track record towards achieving health equity for all Americans.
By focusing on six specific diseases which mostly do not have medical solutions, the CDC has ignored many deadly diseases that can be completely and easily prevented, such as liver cancer.
Ending liver cancer is the most winnable battle in American healthcare today. Up to 80% of all liver cancers globally are caused by hepatitis B (HBV), while hepatitis C (HCV) is the greatest cause of liver cancer in the U.S. There is a vaccine that prevents hepatitis B infection and an actual cure for the hepatitis C virus. Hepatitis B and liver cancer are the greatest health disparity for Asian/Pacific Islander Americans, yet CDC has ignored their own data and in the past refused to even list hepatitis B as a leading American health disparity.
U.S. Speaker Nancy Pelosi has highlighted the Hep B Free model and President Barack Obama has singled out the priority of ending hepatitis B disease for Asian Pacific Americans. In addition, CDC has previously recognized hepatitis B interventions of the Hep B Free movement as 'one of the finest examples of community mobilization' in public health today.
Yet Dr. Frieden misses the boat and ignores up to 5 million Americans with chronic viral hepatitis. The health and well-being of the American people require that the CDC immediately recognize liver cancer and hepatitis B disease as the MOST WINNABLE BATTLE IN AMERICAN HEALTHCARE today."
The AsianWeek Foundation (http://www.asianweek.com/) is a non-profit dedicated to promoting and developing the identity and diversity of the Asian Pacific American community.
The Hep B Free (http://www.sfhepbfree.org/) movement started in San Francisco and is expanding to counties across America. It is a full-spectrum healthcare intervention program to end hepatitis B disease, and brings together community, healthcare, the private sector and government.
SOURCE The AsianWeek Foundation
Source
Also See:
-- NVHR: In Fighting for 'Six Winnable Battles,' CDC May Lose the Nation's Overall Public-Health War
-- CDC chief picks 6 'winnable battles' in health
SAN FRANCISCO, Oct. 5 /PRNewswire/ -- In response to the Centers for Disease Control (CDC) Director Dr. Thomas Frieden's declaration of "six winnable battles" as healthcare priorities, Ted Fang, Director, AsianWeek Foundation and Co-Founder, Hep B Free movement, released the following statement:
"CDC's new prioritization of 'six winnable battles' once again demonstrates their poor track record towards achieving health equity for all Americans.
By focusing on six specific diseases which mostly do not have medical solutions, the CDC has ignored many deadly diseases that can be completely and easily prevented, such as liver cancer.
Ending liver cancer is the most winnable battle in American healthcare today. Up to 80% of all liver cancers globally are caused by hepatitis B (HBV), while hepatitis C (HCV) is the greatest cause of liver cancer in the U.S. There is a vaccine that prevents hepatitis B infection and an actual cure for the hepatitis C virus. Hepatitis B and liver cancer are the greatest health disparity for Asian/Pacific Islander Americans, yet CDC has ignored their own data and in the past refused to even list hepatitis B as a leading American health disparity.
U.S. Speaker Nancy Pelosi has highlighted the Hep B Free model and President Barack Obama has singled out the priority of ending hepatitis B disease for Asian Pacific Americans. In addition, CDC has previously recognized hepatitis B interventions of the Hep B Free movement as 'one of the finest examples of community mobilization' in public health today.
Yet Dr. Frieden misses the boat and ignores up to 5 million Americans with chronic viral hepatitis. The health and well-being of the American people require that the CDC immediately recognize liver cancer and hepatitis B disease as the MOST WINNABLE BATTLE IN AMERICAN HEALTHCARE today."
The AsianWeek Foundation (http://www.asianweek.com/) is a non-profit dedicated to promoting and developing the identity and diversity of the Asian Pacific American community.
The Hep B Free (http://www.sfhepbfree.org/) movement started in San Francisco and is expanding to counties across America. It is a full-spectrum healthcare intervention program to end hepatitis B disease, and brings together community, healthcare, the private sector and government.
SOURCE The AsianWeek Foundation
Source
Also See:
-- NVHR: In Fighting for 'Six Winnable Battles,' CDC May Lose the Nation's Overall Public-Health War
-- CDC chief picks 6 'winnable battles' in health
Human Genome, Novartis Stop Development of Hepatitis C Treatment
By Jennifer Booton
Published October 05, 2010
FOXBusiness
Human Genome Sciences (HGSI: 30.12 ,+0.65 ,+2.21%) and partner Novartis (NVS: 57.74 ,+0.72 ,+1.26%) have terminated development of their Zalbin drug studied as a potential treatment for chronic hepatitis C.
Development was halted after Rockville, Maryland-based Human Genome received a “complete response letter” from the Food and Drug Administration, often seen as a request for more information regarding a drug application.
The company had a Biologics License Application for 900-mcg Zalbin dosed every two weeks.
In May, the company had said it did not expect to achieve FDA approval at its current dosage.
That view followed a “discipline review letter” in which the FDA voiced safety concerns about the specific dosage.
Source
Published October 05, 2010
FOXBusiness
Human Genome Sciences (HGSI: 30.12 ,+0.65 ,+2.21%) and partner Novartis (NVS: 57.74 ,+0.72 ,+1.26%) have terminated development of their Zalbin drug studied as a potential treatment for chronic hepatitis C.
Development was halted after Rockville, Maryland-based Human Genome received a “complete response letter” from the Food and Drug Administration, often seen as a request for more information regarding a drug application.
The company had a Biologics License Application for 900-mcg Zalbin dosed every two weeks.
In May, the company had said it did not expect to achieve FDA approval at its current dosage.
That view followed a “discipline review letter” in which the FDA voiced safety concerns about the specific dosage.
Source
Profectus BioSciences, Inc. Receives $4.4M in Grants to Develop an HIV Prophylactic Vaccine
October 05, 2010 08:30 AM Eastern Daylight Time
Funding will support further evaluation of the TSV approach that has generated significant protective responses in several pre-clinical models of HIV
BALTIMORE--(BUSINESS WIRE)--Profectus BioSciences, Inc., a technology based vaccine company devoted to the treatment and prevention of chronic viral diseases, today announced the award of a Fast Track SBIR from the Division of AIDS, National Institutes of Health for $3.1M to support the development of the Company’s Transition State Vaccine (TSV) technology for a prophylactic HIV Vaccine. This new award builds upon the $1.3M that the Company has also received through collaborative grants awarded to Dr. Robert Gallo, Director of the Institute of Human Virology (IHV) of the University of Maryland School of Medicine, with his co-workers Drs. George Lewis and Anthony DeVico from the National Cancer Institute and other groups. Profectus BioSciences is dedicated to harnessing the immune system to treat and prevent viral diseases and cancers through the delivery of proprietary prime/boost vaccines.
Originally developed at the IHV, the TSV strategy targets the adaptive immune response to the most protected portions of HIV envelope spikes that are considered the “Achilles heel” of all HIV isolates. The TSV is being developed as a subunit protein and also for delivery utilizing the Company’s plasmid DNA and recombinant Vesicular Stomatitis Virus vaccine vectors. Thus far, the TSV approach has generated significant protective responses in several non-human primate models for HIV. This data was presented at the 2010 AIDS Vaccine Conference in Atlanta, GA. John Eldridge, Chief Scientific Officer of Profectus BioSciences, commented, “Awards such as these are central to our ability to pursue an effective prophylactic vaccine against HIV.”
About Profectus BioSciences, Inc.
Profectus BioSciences, Inc. is a technology based vaccine company devoted to the treatment and prevention of chronic viral diseases with a goal of reducing morbidity and mortality. Since its inception in 2003, the Company’s strategic intent has been to develop and acquire the technologies needed to deliver on that mission within high value markets. The foundation of Profectus Biosciences’ approach is the premise that effective management of inflammation and immunity can dramatically improve clinical outcomes. The Company has in-licensed a group of vaccine-based technologies from Wyeth Vaccines that greatly accelerate its’ ability to deliver highly effective therapeutic vaccines based on a “prime-boost” strategy. This strategy uses the delivery of a best-in-class plasmid DNA (pDNA) vaccine to “prime” the immune system, followed by a first-in-class “boost” using a recombinant Vesicular Stomatitis Virus (rVSV) vector. Current disease and virus targets include Hepatitis C Virus (HCV), Human Papilloma Virus (HPV), Herpes Simplex Virus type 2 (HSV-2), and Human Immunodeficiency Virus (HIV), and Malaria.
Source
Funding will support further evaluation of the TSV approach that has generated significant protective responses in several pre-clinical models of HIV
BALTIMORE--(BUSINESS WIRE)--Profectus BioSciences, Inc., a technology based vaccine company devoted to the treatment and prevention of chronic viral diseases, today announced the award of a Fast Track SBIR from the Division of AIDS, National Institutes of Health for $3.1M to support the development of the Company’s Transition State Vaccine (TSV) technology for a prophylactic HIV Vaccine. This new award builds upon the $1.3M that the Company has also received through collaborative grants awarded to Dr. Robert Gallo, Director of the Institute of Human Virology (IHV) of the University of Maryland School of Medicine, with his co-workers Drs. George Lewis and Anthony DeVico from the National Cancer Institute and other groups. Profectus BioSciences is dedicated to harnessing the immune system to treat and prevent viral diseases and cancers through the delivery of proprietary prime/boost vaccines.
Originally developed at the IHV, the TSV strategy targets the adaptive immune response to the most protected portions of HIV envelope spikes that are considered the “Achilles heel” of all HIV isolates. The TSV is being developed as a subunit protein and also for delivery utilizing the Company’s plasmid DNA and recombinant Vesicular Stomatitis Virus vaccine vectors. Thus far, the TSV approach has generated significant protective responses in several non-human primate models for HIV. This data was presented at the 2010 AIDS Vaccine Conference in Atlanta, GA. John Eldridge, Chief Scientific Officer of Profectus BioSciences, commented, “Awards such as these are central to our ability to pursue an effective prophylactic vaccine against HIV.”
About Profectus BioSciences, Inc.
Profectus BioSciences, Inc. is a technology based vaccine company devoted to the treatment and prevention of chronic viral diseases with a goal of reducing morbidity and mortality. Since its inception in 2003, the Company’s strategic intent has been to develop and acquire the technologies needed to deliver on that mission within high value markets. The foundation of Profectus Biosciences’ approach is the premise that effective management of inflammation and immunity can dramatically improve clinical outcomes. The Company has in-licensed a group of vaccine-based technologies from Wyeth Vaccines that greatly accelerate its’ ability to deliver highly effective therapeutic vaccines based on a “prime-boost” strategy. This strategy uses the delivery of a best-in-class plasmid DNA (pDNA) vaccine to “prime” the immune system, followed by a first-in-class “boost” using a recombinant Vesicular Stomatitis Virus (rVSV) vector. Current disease and virus targets include Hepatitis C Virus (HCV), Human Papilloma Virus (HPV), Herpes Simplex Virus type 2 (HSV-2), and Human Immunodeficiency Virus (HIV), and Malaria.
Source
Celsion Receives Positive FDA Guidance for its New Drug Application for ThermoDox to Treat Primary Liver Cancer
From the PharmaLive.com News Archive - Oct. 04, 2010
FDA confirms Celsion's preclinical studies are sufficient to support NDA submission
COLUMBIA, Md., Oct. 4 /PRNewswire/ -- Celsion Corporation (Nasdaq: CLSN), a leading oncology drug development company, announced that the Company has reached agreement with the U.S. Food and Drug Administration (FDA) that the requirements for non-clinical studies have been met for the New Drug Application (NDA) of ThermoDox.
The FDA has provided written guidance that the Company is not required to conduct any additional non-clinical pharmacology, safety pharmacology and general toxicology studies assuming the results of current studies are adequate. The results of these current studies will be reviewed at the time of NDA submission. This agreement takes advantage of an NDA application known as a 505(b)2 which allows a company to reference existing data regarding doxorubicin and other liposomal drugs currently approved by the FDA.
As previously announced, the FDA has granted Fast Track Development for the Company's 600 patient pivotal Phase III clinical trial (the HEAT study) of its investigational drug, ThermoDox®, in combination with radiofrequency ablation (RFA), The Fast Track Development Program provides for expedited regulatory review including frequent interactions between the FDA. Celsion is eligible to submit its NDA on a rolling basis and review sections of the NDA with the FDA in advance of submitting the complete submission. The HEAT study is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA.
"We are very pleased with the FDA's continued willingness to work closely with the Company to identify the most expeditious regulatory pathway forward for ThermoDox® in HCC, a life threatening disorder," stated Mr. Michael H. Tardugno, Celsion's President and Chief Executive Officer. "Our past consultation with the FDA regarding Chemistry Manufacturing and Controls (CMC) has permitted Celsion to implement and validate process improvements to its manufacturing methods used to produce ThermoDox at commercial scale."
About ThermoDox® and the Phase III HEAT Study
ThermoDox® is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers. In the HEAT study, ThermoDox is administered intravenously in combination with RFA. A thermal zone created by the RFA releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially at the targeted tumor.
For primary liver cancer, ThermoDox® is being evaluated in a 600 patient global Phase III study at 75 clinical sites under an FDA Special Protocol Assessment. The study is designed to evaluate the efficacy of ThermoDox in combination with RFA when compared to patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival (PFS) with a secondary confirmatory endpoint of overall survival. A pre-planned, interim efficacy analysis will be performed by an independent Data Monitoring Committee when enrollment in the trial is complete and 50 percent of the PFS events are realized in the study population. Additional information on the Company's ThermoDox® clinical studies may be found at http://www.clinicaltrials.gov/
About Primary Liver Cancer
Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most common solid tumor cancer. The incidence of primary liver cancer is approximately 20,000 cases per year in the United States and has a worldwide incidence of approximately 650,000 cases, due to the high prevalence of Hepatitis B and C in developing countries. The standard first line treatment for liver cancer is surgical resection of the tumor; however 80% to 90% of patients are ineligible for surgery. Radio frequency ablation (RFA) has increasingly become the standard of care for non-resectable liver tumors, but the treatment becomes less effective for larger tumors. There are few non-surgical therapeutic treatment options available as radiation therapy and chemotherapy are largely ineffective in the treatment of primary liver cancer.
About Celsion
Celsion is a leading oncology company dedicated to the development and commercialization of innovative cancer drugs including tumor-targeting treatments using focused heat energy in combination with heat-activated drug delivery systems. Celsion has research, license, or commercialization agreements with leading institutions such as the National Institutes of Health, Duke University Medical Center, University of Hong Kong, Cleveland Clinic, and the North Shore Long Island Jewish Health System. For more information on Celsion, visit our website: http://www.celsion.com/.
Celsion wishes to inform readers that forward-looking statements in this release are made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Readers are cautioned that such forward-looking statements involve risks and uncertainties including, without limitation, unforeseen changes in the course of research and development activities and in clinical trials by others; possible acquisitions of other technologies, assets or businesses; possible actions by customers, suppliers, competitors, regulatory authorities; and other risks detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission.
Click here to view the associated table
SOURCE Celsion Corporation
CONTACT: Marcy Nanus, The Trout Group, +1-646-378-2927, mnanus@troutgroup.com
Web Site: http://www.celsion.com/
Source
Also See:
Celsion Receives Fast Track Designation for ThermoDox® Development Program to Treat Primary Liver Cancer
FDA confirms Celsion's preclinical studies are sufficient to support NDA submission
COLUMBIA, Md., Oct. 4 /PRNewswire/ -- Celsion Corporation (Nasdaq: CLSN), a leading oncology drug development company, announced that the Company has reached agreement with the U.S. Food and Drug Administration (FDA) that the requirements for non-clinical studies have been met for the New Drug Application (NDA) of ThermoDox.
The FDA has provided written guidance that the Company is not required to conduct any additional non-clinical pharmacology, safety pharmacology and general toxicology studies assuming the results of current studies are adequate. The results of these current studies will be reviewed at the time of NDA submission. This agreement takes advantage of an NDA application known as a 505(b)2 which allows a company to reference existing data regarding doxorubicin and other liposomal drugs currently approved by the FDA.
As previously announced, the FDA has granted Fast Track Development for the Company's 600 patient pivotal Phase III clinical trial (the HEAT study) of its investigational drug, ThermoDox®, in combination with radiofrequency ablation (RFA), The Fast Track Development Program provides for expedited regulatory review including frequent interactions between the FDA. Celsion is eligible to submit its NDA on a rolling basis and review sections of the NDA with the FDA in advance of submitting the complete submission. The HEAT study is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA.
"We are very pleased with the FDA's continued willingness to work closely with the Company to identify the most expeditious regulatory pathway forward for ThermoDox® in HCC, a life threatening disorder," stated Mr. Michael H. Tardugno, Celsion's President and Chief Executive Officer. "Our past consultation with the FDA regarding Chemistry Manufacturing and Controls (CMC) has permitted Celsion to implement and validate process improvements to its manufacturing methods used to produce ThermoDox at commercial scale."
About ThermoDox® and the Phase III HEAT Study
ThermoDox® is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers. In the HEAT study, ThermoDox is administered intravenously in combination with RFA. A thermal zone created by the RFA releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially at the targeted tumor.
For primary liver cancer, ThermoDox® is being evaluated in a 600 patient global Phase III study at 75 clinical sites under an FDA Special Protocol Assessment. The study is designed to evaluate the efficacy of ThermoDox in combination with RFA when compared to patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival (PFS) with a secondary confirmatory endpoint of overall survival. A pre-planned, interim efficacy analysis will be performed by an independent Data Monitoring Committee when enrollment in the trial is complete and 50 percent of the PFS events are realized in the study population. Additional information on the Company's ThermoDox® clinical studies may be found at http://www.clinicaltrials.gov/
About Primary Liver Cancer
Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most common solid tumor cancer. The incidence of primary liver cancer is approximately 20,000 cases per year in the United States and has a worldwide incidence of approximately 650,000 cases, due to the high prevalence of Hepatitis B and C in developing countries. The standard first line treatment for liver cancer is surgical resection of the tumor; however 80% to 90% of patients are ineligible for surgery. Radio frequency ablation (RFA) has increasingly become the standard of care for non-resectable liver tumors, but the treatment becomes less effective for larger tumors. There are few non-surgical therapeutic treatment options available as radiation therapy and chemotherapy are largely ineffective in the treatment of primary liver cancer.
About Celsion
Celsion is a leading oncology company dedicated to the development and commercialization of innovative cancer drugs including tumor-targeting treatments using focused heat energy in combination with heat-activated drug delivery systems. Celsion has research, license, or commercialization agreements with leading institutions such as the National Institutes of Health, Duke University Medical Center, University of Hong Kong, Cleveland Clinic, and the North Shore Long Island Jewish Health System. For more information on Celsion, visit our website: http://www.celsion.com/.
Celsion wishes to inform readers that forward-looking statements in this release are made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Readers are cautioned that such forward-looking statements involve risks and uncertainties including, without limitation, unforeseen changes in the course of research and development activities and in clinical trials by others; possible acquisitions of other technologies, assets or businesses; possible actions by customers, suppliers, competitors, regulatory authorities; and other risks detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission.
Click here to view the associated table
SOURCE Celsion Corporation
CONTACT: Marcy Nanus, The Trout Group, +1-646-378-2927, mnanus@troutgroup.com
Web Site: http://www.celsion.com/
Source
Also See:
Celsion Receives Fast Track Designation for ThermoDox® Development Program to Treat Primary Liver Cancer
Microarchitecture of the liver: A Jigsaw puzzle
Marcos Rojkinda, George Philipsb, Anna Mae Diehlb
Received 27 August 2010; accepted 1 September 2010. published online 04 October 2010.
Uncorrected Proof
COMMENTARY ON:
Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration. Hoehme S, Brulport M, Bauer A, Bedawy E, Schormann W, Hermes M, Puppe V, Gebhardt R, Zellmer S, Schwarz M, Bockamp E, Timmel T, Hengstler JG, Drasdo D. Proc Natl Acad Sci USA 2010 Jun 8;107(23):10371–10376. Copyright (2010) by the National Academy of Sciences; USA. Abstract reprinted with permission from the National Academy of Sciences.
Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl(4), a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16day regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named “hepatocyte-sinusoid alignment” (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues.
a Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, DC, United States
b Division of Gatroenterology, Duke University Medical Center, Durham, NC, United States
Corresponding author.
PII: S0168-8278(10)00846-9
doi:10.1016/j.jhep.2010.09.004
© 2010 Published by Elsevier Inc.
Source
Received 27 August 2010; accepted 1 September 2010. published online 04 October 2010.
Uncorrected Proof
COMMENTARY ON:
Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration. Hoehme S, Brulport M, Bauer A, Bedawy E, Schormann W, Hermes M, Puppe V, Gebhardt R, Zellmer S, Schwarz M, Bockamp E, Timmel T, Hengstler JG, Drasdo D. Proc Natl Acad Sci USA 2010 Jun 8;107(23):10371–10376. Copyright (2010) by the National Academy of Sciences; USA. Abstract reprinted with permission from the National Academy of Sciences.
Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl(4), a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16day regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named “hepatocyte-sinusoid alignment” (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues.
a Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, DC, United States
b Division of Gatroenterology, Duke University Medical Center, Durham, NC, United States
Corresponding author.
PII: S0168-8278(10)00846-9
doi:10.1016/j.jhep.2010.09.004
© 2010 Published by Elsevier Inc.
Source
Clinical trial: oral zinc in hepatic encephalopathy
Aliment Pharmacol Ther. 2010 Sep 3. doi: 10.1111/j.1365-2036.2010.04448.x. [Epub ahead of print]
Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H.
Department of Gastroenterology, Kurashiki Central Hospital, Okayama, Japan. Department of Internal Medicine, National Hospital Organization Iwakuni Center, Yamaguchi, Japan. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. Department of Clinical Research, National Hospital Organization Iwakuni Clinical Center, Yamaguchi, Japan.
Abstract
Background Hepatic encephalopathy has a negative effect on patient health-related quality of life (HRQOL). Zinc supplementation has been effective with regard to altered nitrogen metabolism. Aim To investigate the effectiveness of oral zinc supplementation on hepatic encephalopathy and HRQOL. Methods Seventy-nine cirrhotic patients with hepatic encephalopathy were randomized to receive 225 mg of polaprezinc in addition to standard therapies of a protein-restricted diet including branched-chain amino acid and lactulose, or to continue only standard therapies for 6 months. The change of HRQOL by Short Form-36, hepatic encephalopathy grade, laboratory parameters, and neuropsychological (NP) tests were compared at baseline and at 6 months. We also evaluated via multivariate analysis whether zinc supplementation and clinical variables correlated with the changes in physical component scale (PCS) and mental component scale (MCS) between the two visits. Results Zinc supplementation significantly improved the PCS (P = 0.04), but not the MCS (P = 0.95). Zinc supplementation significantly decreased hepatic encephalopathy grade and blood ammonia levels (P = 0.03 and P = 0.01), and improved Child-Pugh score and NP tests compared with standard therapy (P = 0.04 and P = 0.02). In multivariate analysis, zinc supplementation was significantly associated with improvement in PCS (P = 0.03), whereas it was not significantly associated with change in MCS (P = 0.98). Conclusion Zinc supplementation is effective in hepatic encephalopathy and consequently improves patients HRQOL.
PMID: 20822500 [PubMed - as supplied by publisher]
Source
Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H.
Department of Gastroenterology, Kurashiki Central Hospital, Okayama, Japan. Department of Internal Medicine, National Hospital Organization Iwakuni Center, Yamaguchi, Japan. Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. Department of Clinical Research, National Hospital Organization Iwakuni Clinical Center, Yamaguchi, Japan.
Abstract
Background Hepatic encephalopathy has a negative effect on patient health-related quality of life (HRQOL). Zinc supplementation has been effective with regard to altered nitrogen metabolism. Aim To investigate the effectiveness of oral zinc supplementation on hepatic encephalopathy and HRQOL. Methods Seventy-nine cirrhotic patients with hepatic encephalopathy were randomized to receive 225 mg of polaprezinc in addition to standard therapies of a protein-restricted diet including branched-chain amino acid and lactulose, or to continue only standard therapies for 6 months. The change of HRQOL by Short Form-36, hepatic encephalopathy grade, laboratory parameters, and neuropsychological (NP) tests were compared at baseline and at 6 months. We also evaluated via multivariate analysis whether zinc supplementation and clinical variables correlated with the changes in physical component scale (PCS) and mental component scale (MCS) between the two visits. Results Zinc supplementation significantly improved the PCS (P = 0.04), but not the MCS (P = 0.95). Zinc supplementation significantly decreased hepatic encephalopathy grade and blood ammonia levels (P = 0.03 and P = 0.01), and improved Child-Pugh score and NP tests compared with standard therapy (P = 0.04 and P = 0.02). In multivariate analysis, zinc supplementation was significantly associated with improvement in PCS (P = 0.03), whereas it was not significantly associated with change in MCS (P = 0.98). Conclusion Zinc supplementation is effective in hepatic encephalopathy and consequently improves patients HRQOL.
PMID: 20822500 [PubMed - as supplied by publisher]
Source
Cal State Long Beach gets grant to study faster HIV, syphilis, hepatitis C tests
By Kelly Puente, Staff Writer
Posted: 10/04/2010 04:12:08 PM PDT
Updated: 10/04/2010 04:59:32 PM PDT
LONG BEACH - Cal State Long Beach has been awarded a $1.7 million research grant to study the accuracy and acceptability of rapid tests for HIV, hepatitis C and syphilis, officials said.
Through rapid testing a patient is able to receive results on the same day they are tested.
Currently, there are no rapid tests available in the United States for syphilis or combined tests for HIV and hepatitis C. While the there are rapid tests available for HIV, newer, more accurate tests have been developed and are awaiting approval from the Federal Drug Administration.
Officials say rapid testing could increase the number of those receiving test results and could in turn help prevent the spread of infectious diseases.
"Traditional testing for infectious diseases requires clients to return for their test results one or two weeks after providing a sample. But, there are many people who don't return to get their results," said Dennis Fisher, director of behavioral research at Cal State Long Beach. "We believe this project can have a significant impact on the future of screening for infectious diseases in the U.S."
The project, which started on Thursday, will help the FDA gain a better understanding of who selects rapid tests and why. It could lead to the FDA's approval of the experimental tests, officials said.
The project will examine the accuracy and acceptability of six rapid tests for HIV, syphilis, and/or hepatitis C among high-risk groups including gay men, bisexual men and injection drug users.
Fisher believes the combined test for HIV and hepatitis C could be especially helpful in preventing the spread of disease among injected-drug users because it encourages HIV testing in the population.
The four-year grant for the school's Center for Behavioral Research and Services was funded by the National Institute on Drug Abuse.
kelly.puente@presstelegram.com, (562) 499-1305
Source
Posted: 10/04/2010 04:12:08 PM PDT
Updated: 10/04/2010 04:59:32 PM PDT
LONG BEACH - Cal State Long Beach has been awarded a $1.7 million research grant to study the accuracy and acceptability of rapid tests for HIV, hepatitis C and syphilis, officials said.
Through rapid testing a patient is able to receive results on the same day they are tested.
Currently, there are no rapid tests available in the United States for syphilis or combined tests for HIV and hepatitis C. While the there are rapid tests available for HIV, newer, more accurate tests have been developed and are awaiting approval from the Federal Drug Administration.
Officials say rapid testing could increase the number of those receiving test results and could in turn help prevent the spread of infectious diseases.
"Traditional testing for infectious diseases requires clients to return for their test results one or two weeks after providing a sample. But, there are many people who don't return to get their results," said Dennis Fisher, director of behavioral research at Cal State Long Beach. "We believe this project can have a significant impact on the future of screening for infectious diseases in the U.S."
The project, which started on Thursday, will help the FDA gain a better understanding of who selects rapid tests and why. It could lead to the FDA's approval of the experimental tests, officials said.
The project will examine the accuracy and acceptability of six rapid tests for HIV, syphilis, and/or hepatitis C among high-risk groups including gay men, bisexual men and injection drug users.
Fisher believes the combined test for HIV and hepatitis C could be especially helpful in preventing the spread of disease among injected-drug users because it encourages HIV testing in the population.
The four-year grant for the school's Center for Behavioral Research and Services was funded by the National Institute on Drug Abuse.
kelly.puente@presstelegram.com, (562) 499-1305
Source
A conversation with Dr. Grace McComsey, Rainbow Babies pediatric HIV/AIDS researcher
Published: Tuesday, October 05, 2010, 4:00 AM Updated: Tuesday, October 05, 2010, 6:32 AM
Angela Townsend, The Plain Dealer
A Q&A with Dr. Grace McComsey, chief Pediatric Infectious Diseases, Rheumatology, and Global Health at University Hospitals Rainbow Babies & Children's Hospital.
What is the life expectancy of a child born with HIV/AIDS?
The answer is not known. It's still short of the normal population because of co-morbidities like heart disease, liver disease, kidney disease. Any patient who is compliant with treatments is expected to live [a relatively normal life expectancy.] But the two big co-morbidities are heart disease and cancers.
Is HIV preventable in unborn babies?
Yes. Pediatric HIV is 100 percent preventable. That's why screening is so important. If a mother takes her medications and complies with treatment, yes.
What is the status of HIV studies involving children?
Any research of kids and HIV always lags behind adults.
For cardiovascular disease, my group tried to get ahead of the curve. Initially, we had a hard time getting funding [because of] all of this skepticism of the cardiovascular disease risk in kids. But we've already generated several papers and we've really changed the mentality of doctors treating patients.
Is there really a cardiovascular risk in children?
The youngest person [at Rainbow] who had a heart attack was a 24-year-old with HIV. It's true that a 10- or 15-year-old is not having a heart attack, but a 24-year-old with no risk factor had a huge heart attack. This was 4-5 years ago. At that time, we were not as aware as we are now.
Who are the pediatric HIV patients in your study? [Note: McComsey is leading a four-year study that is trying to determine the causes of heart problems in HIV-positive children].
All but one was born with HIV. They all started medication early on. They average [nine years of taking medication] by the time the study started.
Their viral loads are very low. They are doing well from an HIV point of view.
Their CD4 count (the number of CD4 cells a blood sample; the higher the number, the better one's immune system is able to fight off the disease) is very good. This is a good population, a compliant population. No opportunistic infections.
A lot of (the patients) were obese. People have worried so much about wasting that now they don't watch what they eat. They're at the other extreme now.
[Note: Wasting is a condition marked in AIDS patients by the loss of at least 10 percent of one's body weight, and/or severe diarrhea, weakness and fever.]
What have been some of the medical gains in diagnosing and treating newborns and babies?
The diagnosis used to be that you can't really rule out HIV until the child is 18 months of age. You could carry the antibody and [not have it show up] until 18 months. Now we can diagnose by 3 months. I can tell 100 percent if they have it or not when they are born with a blood test when they're born, another blood test at 1 month and a third test at 3 months.
[Note: HIV testing at birth is not done automatically. Parental consent must be provided before the test can be administered.]
Is there a typical regimen of drugs for kids?
There are three different medications, sometimes four, to start. They have to take them twice a day, in contrast with adults who could take one pill, once a day.
At Rainbow, the youngest kid in the study was treated at 9 days old, as soon as he was diagnosed with HIV. You don't want the immune system to take a hit. We can give them oral medications through a tube.
How does treating children differ from treating adults?
Taking care of HIV-infected kids is harder. There are very few drugs in suspension (liquid) form. Domestically, they're not available. All of the money for pediatric HIV [care] is going overseas. We still have a domestic issue.
How do the drugs and the HIV itself impact other areas of health in children?
The long term complications of HIV treatment in kids and adults include lipodystrophy (an abnormal change in body composition with either fat loss or fat build up) due to old medications such as AZT. It also causes mitochondrial toxicity (damage that decreases the number of mitochondria, which provide the body's cells with energy) which is shown to increase depression and decrease quality of life.
Kids stop taking their meds because of lipodystrophy. These meds are keeping them alive but there are complications. In adults we're using newer drugs but in kids we are obligated to use the older drugs.
Tenofovir has really replaced AZT but it does not come in suspension form for kids.
How did you get into this field?
I trained at Case in infectious diseases at a time when we had a lot of sick HIV patients. During my training we lost five HIV kids. Sometimes some cases really hit you. One was a 10-year-old, so cute! I just saw him wasting and wasting, and then dying. He was a hemophiliac and got it through a blood transfusion. It just broke my heart.
HIV is really my passion. I wanted to make a difference. That's why I got into that field.
-- Angela Townsend
Source
Angela Townsend, The Plain Dealer
A Q&A with Dr. Grace McComsey, chief Pediatric Infectious Diseases, Rheumatology, and Global Health at University Hospitals Rainbow Babies & Children's Hospital.
What is the life expectancy of a child born with HIV/AIDS?
The answer is not known. It's still short of the normal population because of co-morbidities like heart disease, liver disease, kidney disease. Any patient who is compliant with treatments is expected to live [a relatively normal life expectancy.] But the two big co-morbidities are heart disease and cancers.
Is HIV preventable in unborn babies?
Yes. Pediatric HIV is 100 percent preventable. That's why screening is so important. If a mother takes her medications and complies with treatment, yes.
What is the status of HIV studies involving children?
Any research of kids and HIV always lags behind adults.
For cardiovascular disease, my group tried to get ahead of the curve. Initially, we had a hard time getting funding [because of] all of this skepticism of the cardiovascular disease risk in kids. But we've already generated several papers and we've really changed the mentality of doctors treating patients.
Is there really a cardiovascular risk in children?
The youngest person [at Rainbow] who had a heart attack was a 24-year-old with HIV. It's true that a 10- or 15-year-old is not having a heart attack, but a 24-year-old with no risk factor had a huge heart attack. This was 4-5 years ago. At that time, we were not as aware as we are now.
Who are the pediatric HIV patients in your study? [Note: McComsey is leading a four-year study that is trying to determine the causes of heart problems in HIV-positive children].
All but one was born with HIV. They all started medication early on. They average [nine years of taking medication] by the time the study started.
Their viral loads are very low. They are doing well from an HIV point of view.
Their CD4 count (the number of CD4 cells a blood sample; the higher the number, the better one's immune system is able to fight off the disease) is very good. This is a good population, a compliant population. No opportunistic infections.
A lot of (the patients) were obese. People have worried so much about wasting that now they don't watch what they eat. They're at the other extreme now.
[Note: Wasting is a condition marked in AIDS patients by the loss of at least 10 percent of one's body weight, and/or severe diarrhea, weakness and fever.]
What have been some of the medical gains in diagnosing and treating newborns and babies?
The diagnosis used to be that you can't really rule out HIV until the child is 18 months of age. You could carry the antibody and [not have it show up] until 18 months. Now we can diagnose by 3 months. I can tell 100 percent if they have it or not when they are born with a blood test when they're born, another blood test at 1 month and a third test at 3 months.
[Note: HIV testing at birth is not done automatically. Parental consent must be provided before the test can be administered.]
Is there a typical regimen of drugs for kids?
There are three different medications, sometimes four, to start. They have to take them twice a day, in contrast with adults who could take one pill, once a day.
At Rainbow, the youngest kid in the study was treated at 9 days old, as soon as he was diagnosed with HIV. You don't want the immune system to take a hit. We can give them oral medications through a tube.
How does treating children differ from treating adults?
Taking care of HIV-infected kids is harder. There are very few drugs in suspension (liquid) form. Domestically, they're not available. All of the money for pediatric HIV [care] is going overseas. We still have a domestic issue.
How do the drugs and the HIV itself impact other areas of health in children?
The long term complications of HIV treatment in kids and adults include lipodystrophy (an abnormal change in body composition with either fat loss or fat build up) due to old medications such as AZT. It also causes mitochondrial toxicity (damage that decreases the number of mitochondria, which provide the body's cells with energy) which is shown to increase depression and decrease quality of life.
Kids stop taking their meds because of lipodystrophy. These meds are keeping them alive but there are complications. In adults we're using newer drugs but in kids we are obligated to use the older drugs.
Tenofovir has really replaced AZT but it does not come in suspension form for kids.
How did you get into this field?
I trained at Case in infectious diseases at a time when we had a lot of sick HIV patients. During my training we lost five HIV kids. Sometimes some cases really hit you. One was a 10-year-old, so cute! I just saw him wasting and wasting, and then dying. He was a hemophiliac and got it through a blood transfusion. It just broke my heart.
HIV is really my passion. I wanted to make a difference. That's why I got into that field.
-- Angela Townsend
Source
Hepatitis C Drugs Rated By Consumer Reports
10/4/2010 11:44 AM ET
(RTTNews) - Consumer Reports has published recommendations regarding two drugs used in the treatment of Hepatitis C.
Consumer Reports analyzed the evidence for PegIntron and Pegasys, and found that neither has been shown to be more effective than the other. The magazine said that the two drugs do vary considerably, however, when it comes to price.
PegIntron could save consumers hundreds to thousands of dollars over Pegasys, depending on the dose and length of treatment.
The pegylated interferons can help eliminate the virus from the body, but they are very expensive, costing between $15,000 and $30,000 for a course of treatment.
These drugs can also cause a wide range of side effects, Consumer Reports points out, including flu-like symptoms such as muscle aches, fever, fatigue, depression, diarrhea, nausea, and rashes or other skin-related problems. Life-threatening or fatal problems are rare but include suicide, relapse of drug abuse or overdose and liver failure.
Hepatitis C, which afflicts an estimated four million people in the U.S., can lead to liver damage and death. It is contracted by exposure to contaminated blood and other bodily fluids.
by RTT Staff Writer
For comments and feedback: contact editorial@rttnews.com
Source
(RTTNews) - Consumer Reports has published recommendations regarding two drugs used in the treatment of Hepatitis C.
Consumer Reports analyzed the evidence for PegIntron and Pegasys, and found that neither has been shown to be more effective than the other. The magazine said that the two drugs do vary considerably, however, when it comes to price.
PegIntron could save consumers hundreds to thousands of dollars over Pegasys, depending on the dose and length of treatment.
The pegylated interferons can help eliminate the virus from the body, but they are very expensive, costing between $15,000 and $30,000 for a course of treatment.
These drugs can also cause a wide range of side effects, Consumer Reports points out, including flu-like symptoms such as muscle aches, fever, fatigue, depression, diarrhea, nausea, and rashes or other skin-related problems. Life-threatening or fatal problems are rare but include suicide, relapse of drug abuse or overdose and liver failure.
Hepatitis C, which afflicts an estimated four million people in the U.S., can lead to liver damage and death. It is contracted by exposure to contaminated blood and other bodily fluids.
by RTT Staff Writer
For comments and feedback: contact editorial@rttnews.com
Source
October 4, 2010
NVHR Blasts Arizona Medicaid's 'Inhumane' Policy Depriving Hepatitis C Patients Liver Transplant Coverage
Patient Advocates, Noted Liver Physician Criticize Arizona Policy as Lacking Scientific Basis
WASHINGTON, Oct. 4 /PRNewswire-USNewswire/ -- A controversial new policy by the Arizona Health Care Cost Containment System depriving hepatitis C patients coverage for liver transplants is effectively a death sentence that, left unchecked, could have far-reaching consequences for millions of Americans afflicted with chronic viral hepatitis, the National Viral Hepatitis Roundtable (NVHR) said today. The new coverage exclusion governing liver transplants took effect Friday as part of broader Medicaid coverage changes made by the state of Arizona in response to budgetary pressures.
"The Arizona Medicaid program's decision to deprive hepatitis C patients coverage for liver transplants is inhumane and will have devastating consequences for Arizona's Medicaid beneficiaries," said Ms. Lorren Sandt, NVHR Chair and Executive Director of Caring Ambassadors Program, based in Portland, Oregon. "NVHR recognizes that both public and private health care programs are struggling with the burden of rising costs and a challenging economic environment. However, the cruel costs associated with Arizona's Medicaid coverage changes do not appear to be based on sound science and far exceed any supposed benefit."
"The standard of care for centers and practitioners is to offer liver transplants to patients with hepatitis C. All insurance providers – including state Medicaid programs – need to provide coverage for what is the standard of care. With new curative therapies on the horizon, it is imperative not to discriminate against patients with hepatitis C when selecting patients for a liver transplant," said Robert G. Gish, M.D., Co-Director Center for Hepatobiliary Disease and Abdominal Transplantation (CHAT), University of California, San Diego School of Medicine.
Arizona Medicaid's transplant coverage exclusion is the first of its kind in the nation for hepatitis C patients. NVHR is deeply troubled that the new Medicaid coverage exclusion inflicts catastrophic consequences that go far beyond any supposed savings. According to news reports, Arizona faces a budgetary shortfall this year of as much as $825 million. The entire package of Medicaid benefit changes, including the hepatitis C liver transplant exclusion, is expected to yield about $5 million in savings – or about 1/2 of one percent of the projected budgetary shortfall.
An estimated 5.3 million Americans have been infected with chronic viral hepatitis B or C – and with most unaware of their infection, millions are at risk of developing life-threatening complications, especially African Americans and Asian Americans. Without detection and prompt treatment, chronic viral hepatitis leads to liver cancer, cirrhosis, or liver failure.
NVHR is a coalition of more than 170 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. http://www.nvhr.org/
SOURCE National Viral Hepatitis Roundtable
RELATED LINKS
http://www.nvhr.org/
Source
WASHINGTON, Oct. 4 /PRNewswire-USNewswire/ -- A controversial new policy by the Arizona Health Care Cost Containment System depriving hepatitis C patients coverage for liver transplants is effectively a death sentence that, left unchecked, could have far-reaching consequences for millions of Americans afflicted with chronic viral hepatitis, the National Viral Hepatitis Roundtable (NVHR) said today. The new coverage exclusion governing liver transplants took effect Friday as part of broader Medicaid coverage changes made by the state of Arizona in response to budgetary pressures.
"The Arizona Medicaid program's decision to deprive hepatitis C patients coverage for liver transplants is inhumane and will have devastating consequences for Arizona's Medicaid beneficiaries," said Ms. Lorren Sandt, NVHR Chair and Executive Director of Caring Ambassadors Program, based in Portland, Oregon. "NVHR recognizes that both public and private health care programs are struggling with the burden of rising costs and a challenging economic environment. However, the cruel costs associated with Arizona's Medicaid coverage changes do not appear to be based on sound science and far exceed any supposed benefit."
"The standard of care for centers and practitioners is to offer liver transplants to patients with hepatitis C. All insurance providers – including state Medicaid programs – need to provide coverage for what is the standard of care. With new curative therapies on the horizon, it is imperative not to discriminate against patients with hepatitis C when selecting patients for a liver transplant," said Robert G. Gish, M.D., Co-Director Center for Hepatobiliary Disease and Abdominal Transplantation (CHAT), University of California, San Diego School of Medicine.
Arizona Medicaid's transplant coverage exclusion is the first of its kind in the nation for hepatitis C patients. NVHR is deeply troubled that the new Medicaid coverage exclusion inflicts catastrophic consequences that go far beyond any supposed savings. According to news reports, Arizona faces a budgetary shortfall this year of as much as $825 million. The entire package of Medicaid benefit changes, including the hepatitis C liver transplant exclusion, is expected to yield about $5 million in savings – or about 1/2 of one percent of the projected budgetary shortfall.
An estimated 5.3 million Americans have been infected with chronic viral hepatitis B or C – and with most unaware of their infection, millions are at risk of developing life-threatening complications, especially African Americans and Asian Americans. Without detection and prompt treatment, chronic viral hepatitis leads to liver cancer, cirrhosis, or liver failure.
NVHR is a coalition of more than 170 public, private, and voluntary organizations dedicated to reducing the incidence of infection, morbidity, and mortality from chronic viral hepatitis that afflicts more than 5 million Americans. http://www.nvhr.org/
SOURCE National Viral Hepatitis Roundtable
RELATED LINKS
http://www.nvhr.org/
Source
Dynavax's HEPLISAV Demonstrates Superior Seroprotection in Diabetics Compared to Engerix-B
Late-Breaker AASLD Abstract and New Diabetic Data Published Online
BERKELEY, CA, Oct 04, 2010 (MARKETWIRE via COMTEX) -- In an abstract published today on the website of the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Dynavax Technologies Corporation /quotes/comstock/15*!dvax/quotes/nls/dvax (DVAX 1.89, +0.03, +1.61%) reported that its novel hepatitis B vaccine candidate, HEPLISAV(TM), given as two doses over four weeks demonstrated superior seroprotection in persons with diabetes mellitus compared to Engerix-B given as three doses over 24 weeks. The subset analysis of 62 adults with diabetes in Dynavax's previously reported Phase 3 multicenter study (PHAST or Phase 3 HEPLISAV Short-regimen Trial), showed that at 12 weeks, 84 percent of adult diabetics treated with HEPLISAV achieved seroprotection as compared to 0 percent of adult diabetics treated with Engerix-B. At week 28, 93 percent of the HEPLISAV-treated group versus 35 percent in the Engerix-B group achieved seroprotection. HEPLISAV's significantly higher rate of seroprotection was achieved without further immunization past four weeks while the Engerix-B group received a third immunization at 24 weeks. A poster presentation (LB-17) entitled, "Immunogenicity of Two Doses of Investigational HEPLISAV(TM) Compared to Three Doses of Licensed Hepatitis B Vaccine (ENGERIX-B(R)) in Diabetics", will be made in a late-breaker session on November 1, 2010 at the AASLD in Boston, Massachusetts.
According to Dr. Tyler Martin, President and Chief Medical Officer of Dynavax, "Diabetics are at risk for hepatitis B infection, and once infected, their disease frequently results in more severe chronic illness. The situation is complicated by the fact that patients with diabetes commonly do not respond well to currently licensed hepatitis B vaccines. The data we will report at the AASLD meeting is particularly exciting as our technology clearly represents a potential breakthrough in immunization regimens as well as a means of significantly expanding the number of individuals for whom protection against hepatitis B will be possible.
"It is well known that epidemic outbreaks of hepatitis B have occurred over the last several years in long-term care facilities. However, vaccination against the disease has been limited because patients in this setting simply do not respond to vaccination as well as healthy, younger adults in the general population. The Center for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has been studying the issue for quite some time, and later this month will consider a new recommendation for hepatitis B vaccination of adults with diabetes," Dr. Martin continued.
Dynavax first reported the results of its PHAST multi-center, observer-blinded Phase 3 study in August 2008. Of the 2101 subjects in the overall per protocol study population, the seroprotection rate of the HEPLISAV-treated group was 95 percent at week 12 and 81 percent at week 28 in the Engerix-B group, indicating non-inferiority/superiority of HEPLISAV over Engerix-B. HEPLISAV is Dynavax's novel hepatitis B vaccine candidate, a TLR9 agonist; Engerix-B is a commercially available hepatitis B vaccine.
Engerix-B(R) is a registered trademark of GlaxoSmithKline
About HEPLISAV
HEPLISAV is an investigational adult hepatitis B vaccine. The vaccine candidate is being evaluated in two Phase 3 studies that are directed toward fulfilling licensure requirements in U.S., Canada and Europe. In a completed pivotal Phase 3 trial, HEPLISAV demonstrated increased, rapid protection with fewer doses than current licensed vaccines. Dynavax has worldwide commercial rights to HEPLISAV and is developing the vaccine for large, high-value populations that are less responsive to current licensed vaccines, including individuals with chronic kidney disease. HEPLISAV combines hepatitis B surface antigen with a proprietary Toll-like Receptor 9 agonist known as ISS to enhance the immune response.
About Dynavax
Dynavax Technologies Corporation, a clinical-stage biopharmaceutical company, discovers and develops novel products to prevent and treat infectious diseases. The Company's lead product candidate is HEPLISAV, an investigational adult hepatitis B vaccine designed to enhance protection more rapidly and with fewer doses than current licensed vaccines. For more information visit http://www.dynavax.com/.
Forward Looking Statements
This press release contains "forward-looking statements," including the potential for use of HEPLISAV that are subject to a number of risks and uncertainties. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in our business, including whether the reported results can be replicated in prospective studies, whether successful clinical and regulatory development and approval of HEPLISAV can occur in a timely manner or without significant additional studies or difficulties or delays in development or clinical trial enrollment, whether the studies can support registration for commercialization of HEPLISAV; the results of clinical trials and the impact of those results on the initiation and completion of subsequent trials and issues arising in the regulatory process; the Company's ability to obtain additional financing to support the development and commercialization of HEPLISAV and its other operations, possible claims against the Company based on the patent rights of others; and other risks detailed in the "Risk Factors" section of our current periodic reports with the SEC. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. Information on Dynavax's website at http://www.dynavax.com/ is not incorporated by reference in the Company's current periodic reports with the SEC.
Contact:
Michael Ostrach
Vice President and Chief Business Officer
510-665-7257
Email Contact
Source
BERKELEY, CA, Oct 04, 2010 (MARKETWIRE via COMTEX) -- In an abstract published today on the website of the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Dynavax Technologies Corporation /quotes/comstock/15*!dvax/quotes/nls/dvax (DVAX 1.89, +0.03, +1.61%) reported that its novel hepatitis B vaccine candidate, HEPLISAV(TM), given as two doses over four weeks demonstrated superior seroprotection in persons with diabetes mellitus compared to Engerix-B given as three doses over 24 weeks. The subset analysis of 62 adults with diabetes in Dynavax's previously reported Phase 3 multicenter study (PHAST or Phase 3 HEPLISAV Short-regimen Trial), showed that at 12 weeks, 84 percent of adult diabetics treated with HEPLISAV achieved seroprotection as compared to 0 percent of adult diabetics treated with Engerix-B. At week 28, 93 percent of the HEPLISAV-treated group versus 35 percent in the Engerix-B group achieved seroprotection. HEPLISAV's significantly higher rate of seroprotection was achieved without further immunization past four weeks while the Engerix-B group received a third immunization at 24 weeks. A poster presentation (LB-17) entitled, "Immunogenicity of Two Doses of Investigational HEPLISAV(TM) Compared to Three Doses of Licensed Hepatitis B Vaccine (ENGERIX-B(R)) in Diabetics", will be made in a late-breaker session on November 1, 2010 at the AASLD in Boston, Massachusetts.
According to Dr. Tyler Martin, President and Chief Medical Officer of Dynavax, "Diabetics are at risk for hepatitis B infection, and once infected, their disease frequently results in more severe chronic illness. The situation is complicated by the fact that patients with diabetes commonly do not respond well to currently licensed hepatitis B vaccines. The data we will report at the AASLD meeting is particularly exciting as our technology clearly represents a potential breakthrough in immunization regimens as well as a means of significantly expanding the number of individuals for whom protection against hepatitis B will be possible.
"It is well known that epidemic outbreaks of hepatitis B have occurred over the last several years in long-term care facilities. However, vaccination against the disease has been limited because patients in this setting simply do not respond to vaccination as well as healthy, younger adults in the general population. The Center for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has been studying the issue for quite some time, and later this month will consider a new recommendation for hepatitis B vaccination of adults with diabetes," Dr. Martin continued.
Dynavax first reported the results of its PHAST multi-center, observer-blinded Phase 3 study in August 2008. Of the 2101 subjects in the overall per protocol study population, the seroprotection rate of the HEPLISAV-treated group was 95 percent at week 12 and 81 percent at week 28 in the Engerix-B group, indicating non-inferiority/superiority of HEPLISAV over Engerix-B. HEPLISAV is Dynavax's novel hepatitis B vaccine candidate, a TLR9 agonist; Engerix-B is a commercially available hepatitis B vaccine.
Engerix-B(R) is a registered trademark of GlaxoSmithKline
About HEPLISAV
HEPLISAV is an investigational adult hepatitis B vaccine. The vaccine candidate is being evaluated in two Phase 3 studies that are directed toward fulfilling licensure requirements in U.S., Canada and Europe. In a completed pivotal Phase 3 trial, HEPLISAV demonstrated increased, rapid protection with fewer doses than current licensed vaccines. Dynavax has worldwide commercial rights to HEPLISAV and is developing the vaccine for large, high-value populations that are less responsive to current licensed vaccines, including individuals with chronic kidney disease. HEPLISAV combines hepatitis B surface antigen with a proprietary Toll-like Receptor 9 agonist known as ISS to enhance the immune response.
About Dynavax
Dynavax Technologies Corporation, a clinical-stage biopharmaceutical company, discovers and develops novel products to prevent and treat infectious diseases. The Company's lead product candidate is HEPLISAV, an investigational adult hepatitis B vaccine designed to enhance protection more rapidly and with fewer doses than current licensed vaccines. For more information visit http://www.dynavax.com/.
Forward Looking Statements
This press release contains "forward-looking statements," including the potential for use of HEPLISAV that are subject to a number of risks and uncertainties. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in our business, including whether the reported results can be replicated in prospective studies, whether successful clinical and regulatory development and approval of HEPLISAV can occur in a timely manner or without significant additional studies or difficulties or delays in development or clinical trial enrollment, whether the studies can support registration for commercialization of HEPLISAV; the results of clinical trials and the impact of those results on the initiation and completion of subsequent trials and issues arising in the regulatory process; the Company's ability to obtain additional financing to support the development and commercialization of HEPLISAV and its other operations, possible claims against the Company based on the patent rights of others; and other risks detailed in the "Risk Factors" section of our current periodic reports with the SEC. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. Information on Dynavax's website at http://www.dynavax.com/ is not incorporated by reference in the Company's current periodic reports with the SEC.
Contact:
Michael Ostrach
Vice President and Chief Business Officer
510-665-7257
Email Contact
Source
October 3, 2010
New research reveals possible method for boosting the immune system to protect infants against HIV
October 3, 2010
- Researchers at Oregon Health &Science University may have uncovered a new weapon for combating HIV as it is passed from mother to newborn child. The research, which was led by researchers at OHSU's Oregon National Primate Research Center, will be published in the October 3rd online edition of the journal Nature Medicine.
"Mother-to-infant transmission of HIV is a tremendous worldwide problem, especially in several African nations," said Nancy Haigwood, Ph.D., researcher and director of the Oregon National Primate Research Center at OHSU.
According to the latest data from the World Health Organization, 33.4 million people were infected by the virus in 2008. About 67 percent of the world's infections are in African countries. In addition, 91 percent of the world's childhood infections are in Africa.
Haigwood, her colleagues at OHSU, along with researchers at the University of Washington are investigating strategies for preventing or countering HIV infections in babies born to women with HIV. Their strategy: to educate part of the baby's immune system within the first few hours of birth to better fight of the disease.
"HIV attacks and kills T-cells, the white blood cells that play an important role in the immune system because they have the ability to identify and destroy disease invaders. By attacking the body's natural defenses, the disease progresses, causes AIDS and eventually death," explained Haigwood. "Therefore, many therapies focus on protecting T-cells."
However, Haigwood and her colleagues took a different approach. They focused on another component of the immune system, which was initially thought to play a lesser role in the body's defense against HIV. Babies born to HIV-infected mothers have HIV-specific neutralizing antibodies at the time of birth that are "passively" acquired across the placenta. They wanted to determine whether boosted neutralizing antibody levels would weaken the disease's ability to overtake the body's defenses.
To investigate this possible treatment, the researchers studied three small groups of infant monkeys. The first group was given additional antibodies derived from healthy mothers. The second group was given antibodies matched to simian/human immunodeficiency virus (SHIV). SHIV is a hybrid virus used in research to ensure that results translate between species. The third group of animals was provided with HIV antibodies similar to, but not exactly matching, the strain of infection they would receive. The three groups were then exposed to SHIV and their immune systems were subsequently monitored.
Unlike the other two groups, the "HIV-matched" animals were better protected from the virus. They developed higher levels of neutralizing antibodies and, had lower levels of SHIV in their blood plasma than the comparison groups six months post-infection. In addition they maintained their CD4+ T cells - another component of the immune system.
The study also provided insights into the level of antibodies needed to impact disease progression. For this study, the antibody levels were relatively low dosed. Previously, antibodies were shown to block infection in animal models. This study demonstrated, for the first time, that very low levels of antibodies -- too low to block infection -- can influence disease progression in this setting and stimulate an immune response that contributes to viral control in the absence of drug treatment.
In future studies, the researchers hope to learn whether higher doses of antibodies translate into greater protection for the infants.
"This research demonstrates that boosting the body's HIV antibodies -- by a time-honored method of passive transfer that would use new HIV-specific human monoclonal antibodies -- may be a strategy for reducing infection levels and protecting CD4+ T cells in newborn children," said Haigwood. "While the treatment would not likely prevent infection, it could limit the levels of infection in children which would greatly reduce suffering and extend lives."
Provided by Oregon Health & Science University
Source
- Researchers at Oregon Health &Science University may have uncovered a new weapon for combating HIV as it is passed from mother to newborn child. The research, which was led by researchers at OHSU's Oregon National Primate Research Center, will be published in the October 3rd online edition of the journal Nature Medicine.
"Mother-to-infant transmission of HIV is a tremendous worldwide problem, especially in several African nations," said Nancy Haigwood, Ph.D., researcher and director of the Oregon National Primate Research Center at OHSU.
According to the latest data from the World Health Organization, 33.4 million people were infected by the virus in 2008. About 67 percent of the world's infections are in African countries. In addition, 91 percent of the world's childhood infections are in Africa.
Haigwood, her colleagues at OHSU, along with researchers at the University of Washington are investigating strategies for preventing or countering HIV infections in babies born to women with HIV. Their strategy: to educate part of the baby's immune system within the first few hours of birth to better fight of the disease.
"HIV attacks and kills T-cells, the white blood cells that play an important role in the immune system because they have the ability to identify and destroy disease invaders. By attacking the body's natural defenses, the disease progresses, causes AIDS and eventually death," explained Haigwood. "Therefore, many therapies focus on protecting T-cells."
However, Haigwood and her colleagues took a different approach. They focused on another component of the immune system, which was initially thought to play a lesser role in the body's defense against HIV. Babies born to HIV-infected mothers have HIV-specific neutralizing antibodies at the time of birth that are "passively" acquired across the placenta. They wanted to determine whether boosted neutralizing antibody levels would weaken the disease's ability to overtake the body's defenses.
To investigate this possible treatment, the researchers studied three small groups of infant monkeys. The first group was given additional antibodies derived from healthy mothers. The second group was given antibodies matched to simian/human immunodeficiency virus (SHIV). SHIV is a hybrid virus used in research to ensure that results translate between species. The third group of animals was provided with HIV antibodies similar to, but not exactly matching, the strain of infection they would receive. The three groups were then exposed to SHIV and their immune systems were subsequently monitored.
Unlike the other two groups, the "HIV-matched" animals were better protected from the virus. They developed higher levels of neutralizing antibodies and, had lower levels of SHIV in their blood plasma than the comparison groups six months post-infection. In addition they maintained their CD4+ T cells - another component of the immune system.
The study also provided insights into the level of antibodies needed to impact disease progression. For this study, the antibody levels were relatively low dosed. Previously, antibodies were shown to block infection in animal models. This study demonstrated, for the first time, that very low levels of antibodies -- too low to block infection -- can influence disease progression in this setting and stimulate an immune response that contributes to viral control in the absence of drug treatment.
In future studies, the researchers hope to learn whether higher doses of antibodies translate into greater protection for the infants.
"This research demonstrates that boosting the body's HIV antibodies -- by a time-honored method of passive transfer that would use new HIV-specific human monoclonal antibodies -- may be a strategy for reducing infection levels and protecting CD4+ T cells in newborn children," said Haigwood. "While the treatment would not likely prevent infection, it could limit the levels of infection in children which would greatly reduce suffering and extend lives."
Provided by Oregon Health & Science University
Source
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