Cerus, the University Hospitals of Geneva, and the Transfusion Service of the Swiss Red Cross Intend to Collaborate on Whole Blood Pathogen Inactivation for Africa

30th of April 2012 08:30 EST

Cerus Corporation (NASDAQ:CERS), the University Hospitals of Geneva (HUG) and their Blood Transfusion Center (CTS), and the Transfusion Service of the Swiss Red Cross (Transfusion CRS Suisse or Blutspende SRK Schwietz) announced today their intent to collaborate on adapting the Cerus INTERCEPT Blood System for red cells to enable inactivation of pathogens in whole blood, specifically for the African region. While patients in developed countries receive platelet, plasma or red cell transfusions, in many African countries whole blood transfusions remain common, and require development of pathogen inactivation methods optimized for use in local blood bank facilities.

The African blood supply is challenged by both transfusion-transmitted diseases and a shortage of available units for transfusion. Pathogen inactivation can provide protection from a broad range of transfusion-transmitted diseases without further restricting the scarce supply of blood donors. The collaboration is designed to draw on the distinctive strengths of each organization to seek the funding necessary to develop a whole blood PI system that can be evaluated in clinical use in Africa.

“We believe pathogen inactivation is critical to blood safety everywhere, and we currently use the INTERCEPT system to treat all platelet units produced in Switzerland,”

said Dr. Rudolf Schwabe, chief executive officer of the Transfusion CRS Suisse. “Africa’s blood supply is at risk from many transfusion-transmitted diseases that can be prevented by use of pathogen inactivation. We see a great need in ensuring the safety and availability of blood for those patients in Africa who need it most.” 

“In countries where whole blood transfusions are used to treat acute and chronic anemia as well as post-partum hemorrhage, the opportunity to reduce the risk of bloodborne diseases fits perfectly with the aim of our university hospital policy to develop international medical cooperation, training and humanitarian health actions to improve global health,”

commented Dr. Soraya Amar-El Dusouqui, project director, CTS-HUG (University Hospitals of Geneva).

Blood safety and supply are of major health concern in Africa. Only an estimated 40 percent of the demand for transfusions is currently being supplied (Bloch et al, Transfusion Medicine Reviews, 2012 Apr;26:164-80). Obstetric hemorrhage, sickle cell disease and childhood anemia, HIV, malaria and traffic accidents are among the many indications requiring transfusion as a critical life-saving intervention.

At the same time, local blood donors frequently have significant rates of well-known transfusion-transmitted agents like HIV, HTLV, hepatitis and bacteria, as well as infections endemic to the region including malaria, dengue, Chikungunya and yellow fever.

Unlike other blood safety techniques, pathogen inactivation is able to provide protection from a broad range of viruses, bacteria and parasites from a single added safety step. Cerus’ INTERCEPT systems for platelets and plasma are already used in Europe, the Commonwealth of Independent States (CIS) and the Middle East. The INTERCEPT red cell system is anticipated to begin phase III trials in Europe later this year. To treat whole blood in Africa, a treatment system must be designed to work within the limited infrastructure of local blood banks and hospitals, as well as effectively inactivating bloodborne pathogens.

“We are honored to join HUG, CTS, and SRK in the pursuit of a pathogen inactivation system to improve blood safety in Africa where the technology can have a great impact in improving human health,“ said William ‘Obi’ Greenman, Cerus’ president and chief executive officer.

"Pathogen inactivation is being increasingly used in Europe, CIS and the Middle East, and, like our collaborators in this project, we feel an obligation to bring this technology to regions like Africa where it has the potential to transform blood safety."

ABOUT CERUS

Cerus Corporation is a biomedical products company focused on commercializing the INTERCEPT Blood System to enhance blood safety. The INTERCEPT system is designed to reduce the risk of transfusion-transmitted diseases by inactivating a broad range of pathogens such as viruses, bacteria and parasites that may be present in donated blood. The nucleic acid targeting mechanism of action enables INTERCEPT treatment to inactivate established transfusion threats, such as hepatitis B and C, HIV, West Nile virus and bacteria, and is designed to inactivate emerging pathogens such as influenza, malaria and dengue. Cerus currently markets and sells the INTERCEPT Blood System for both platelets and plasma in Europe, the Commonwealth of Independent States, the Middle East and selected countries in other regions around the world. The INTERCEPT red blood cell system is in clinical development. See http://www.cerus.com for more information.

INTERCEPT and INTERCEPT Blood System are trademarks of Cerus Corporation.

This press release contains forward-looking statements. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements, including, without limitation, statements relating to the intended collaborative activities of the parties, the potential efficacy, development and clinical evaluation of an INTERCEPT system adapted for use with whole blood and the anticipated timing of initiating Phase III INTERCEPT red blood cell studies in Europe. These forward-looking statements are based upon Cerus’ current expectations. Actual results could differ materially from these forward-looking statements as a result of certain factors, including, without limitation, risks associated with development and clinical evaluation of the INTERCEPT system for whole blood and for red blood cells, the risk that available funding may not be available to support whole blood-related activities under the proposed collaboration, risks associated with dependence on third-party potential collaborators to support whole blood-related development activities and other risks detailed in the Cerus' filings with, the Securities and Exchange Commission (SEC), including in Cerus' annual report on Form 10-K for the year ended December 31, 2011, filed with the SEC on March 5, 2012. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Cerus does not undertake any obligation to update any forward-looking statements as a result of new information, future events, changed assumptions or otherwise.

Source

Advances in the Treatment of Hepatitis C Virus Infection

Advances in HCV Treatment Volume 20 Issue 1 April/May 2012

Top Antivir Med. 2012;20(1):5-10
©2012, IAS–USA

Perspective

Advances in HCV Treatment Volume 20 Issue 1 April/May 2012 Since 2007, the annual age-adjusted mortality rate in HIV disease in the United States has been surpassed by that of hepatitis C virus (HCV) disease, reflecting the continuing decline in HIV-related mortality and the continuing increase in HCV-related mortality.1 The prevalence of HCV-related cirrhosis is projected to continue to increase until it reaches a peak around 2020, reflecting what is commonly a 20- to 40-year period between HCV acquisition and the later-stage manifestations of cirrhosis, end-stage liver disease, and liver cancer. These projections assumed no changes in our ability to treat HCV infection. The rate of sustained virologic response (SVR; ie, absence of HCV RNA in blood for 6 months after the end of treatment) with what has been the standard treatment of peginterferon alfa plus ribavirin is approximately 40% in patients with HCV genotype 1 Dr Thomas is Professor of Medicine and Director of the Division of Infectious Diseases at The Johns Hopkins University in Baltimore, MD. Since 2007, the annual age-adjusted mortality rate in hepatitis C virus (HCV) infection in the United States has been greater than that in HIV disease, reflecting the continuing decline in HIV-related mortality and the continuing increase in HCV-related mortality. The approval of 2 new direct-acting antivirals within the past year, as well as the promise offered by numerous other direct-acting agents in development, provides hope that we will be able to markedly improve our ability to cure HCV disease. The addition of a protease inhibitor (PI) to what has been the standard HCV therapy of peginterferon alfa and ribavirin dramatically improves sustained virologic response rates in treatment-naive patients with genotype 1 infection. Similar results have been observed in some treatment-experienced patients in whom prior peginterferon alfa/ribavirin therapy has failed. The use of these new agents has also permitted response-guided therapy, wherein early sustained virologic response to treatment allows for a shortened treatment duration. However, these new PIs add cost and adverse effects to HCV therapy. Boceprevir is associated with increased risk of anemia and dysgeusia, and telaprevir is associated with increased risk of anemia and skin and gastrointestinal adverse effects. Early studies indicate that the addition of PIs results in high response rates in patients with HCV/HIV coinfection. Other studies suggest that combinations of PIs and other direct-acting antivirals may ultimately permit cure when used in interferon sparing regimens. This article summarizes a presentation by David L. Thomas, MD, MPH, at the IAS–USA live continuing medical education course held in New York City in October 2011.

Since 2007, the annual age-adjusted mortality rate in HIV disease in the United States has been surpassed by that of hepatitis C virus (HCV) disease, reflecting the continuing decline in HIV-related mortality and the continuing increase in HCV-related mortality.1 The prevalence of HCV-related cirrhosis is projected to continue to increase until it reaches a peak around 2020, reflecting what is commonly a 20- to 40-year period between HCV acquisition and the later-stage manifestations of cirrhosis, end-stage liver disease, and liver cancer. These projections assumed no changes in our ability to treat HCV infection.

The rate of sustained virologic response (SVR; ie, absence of HCV RNA in blood for 6 months after the end of treatment) with what has been the standard treatment of peginterferon alfa plus ribavirin is approximately 40% in patients with HCV genotype 1 infection, the predominant type of infection in the United States. The rate is less than 30% in HIV/HCV-coinfected patients with HCV genotype 1. However, the past year has brought the approval of 2 new drugs for treating HCV infection—the HCV protease inhibitors boceprevir and telaprevir— and numerous new drugs are in advanced stages of development. It is hoped that these new weapons will allow us to improve the projections for HCV disease outcomes.

Treatment Outcomes With Telaprevir and Boceprevir

Treatment-Naive Patients

In the trial supporting approval of telaprevir, more than 1000 treatment-naive patients with HCV genotype 1 infection were randomly assigned to receive telaprevir for 8 weeks or 12 weeks plus concurrent standard peginterferon alfa/ribavirin therapy for up to 48 weeks, or peginterferon alfa/ribavirin alone for 48 weeks.2 Patients receiving telaprevir who achieved a virologic response that was sustained between weeks 8 and 12 were further randomly assigned to stop peginterferon alfa/ribavirin after week 24 or continue for the full 48 weeks. Overall, cure (ie, SVR) was achieved in 69% of patients receiving 8 weeks of telaprevir and 75% of those receiving 12 weeks of telaprevir, compared with 44% of those receiving peginterferon alfa/ribavirin alone. In black patients, who are known to have lower rates of response to peginterferon alfa/ribavirin, SVR rates were 25% with standard therapy, versus 58% and 62% with 8 weeks and 12 weeks of telaprevir, respectively. Among nonblack patients, SVR rates were 48% with peginterferon alfa/ribavirin, compared with 73% and 79% with the addition of telaprevir for 8 weeks and 12 weeks, respectively.

Patients who stopped therapy at 24 weeks after an early response to telaprevir-containing therapy had outcomes similar to those who continued to receive peginterferon alfa/ribavirin for the full 48-week course. The 12-week course of telaprevir was approved in 2011 by the US Food and Drug Administration (FDA) for use in combination with peginterferon alfa/ ribavirin, as was the shortened treatment duration in patients with early sustained response to treatment.

With regard to the ability to abbreviate therapy based on early response to treatment, Sherman and colleagues performed a study in treatment-naive, genotype 1–infected patients.3 Patients who achieved early rapid virologic response (eRVR; defined as undetectable HCV RNA at week 4 and week 12) with telaprevir plus peginterferon alfa/ribavirin therapy were randomly assigned to continue receiving peginterferon alfa/ribavirin for the full 48 weeks or to stop treatment after a total of 24 weeks. The overall SVR rate was 72%, with 65% of the total of 540 patients achieving eRVR. SVR rates were 92% among those stopping treatment after 24 weeks and 88% among those receiving 48 weeks of treatment. Among those who did not achieve eRVR, the SVR rate was 64%.

In the pivotal boceprevir trial, approximately 1100 treatment-naive patients with genotype 1 infection received a lead-in of peginterferon alfa/ ribavirin for 4 weeks.4 This was followed by either continuation of peginterferon alfa/ribavirin treatment for 44 weeks (total of 48 weeks); addition of boceprevir for 44 weeks (fixed-duration group); or addition of boceprevir for 24 weeks followed by treatment discontinuation if virus was undetectable from 8 weeks to 24 weeks or treatment continuation with peginterferon alfa/ribavirin alone for 20 weeks if virus was detectable (responseguided therapy group). Overall, SVR rates were 63% in the response-guided therapy boceprevir group and 66% in the fixed-duration boceprevir group, compared with 38% in the peginterferon alfa/ribavirin treatment group. SVR rates were improved with the addition of boceprevir in black patients (42% in the response-guided therapy group and 53% in the fixed-duration group vs 23% in the standard treatment group) and nonblack patients (67% and 69% vs 41%, respectively). Boceprevir was approved by the FDA in 2011 for use in combination with peginterferon alfa/ribavirin, including a shortened response-guided course of therapy in treatment-naive patients.

Treatment-Experienced Patients

Telaprevir and boceprevir have each been shown to achieve cure in a substantial proportion of HCV-infected patients in whom prior peginterferon alfa/ribavirin therapy had failed. In a study of more than 600 treatmentexperienced patients, Zeuzem and colleagues found SVR rates of 64% with the combination of 12 weeks of telaprevir plus 48 weeks of peginterferon alfa/ribavirin; 66% with a 4-week lead-in regimen of peginterferon alfa/ ribavirin followed by 12 weeks of telaprevir and 44 weeks of peginterferon alfa/ribavirin; and 17% with retreatment with 48 weeks of peginterferon alfa/ribavirin.5 Among patients with relapse (ie, those who relapsed after having undetectable virus at the end of prior treatment) SVR rates were 83%, 88%, and 24%, respectively. Among those who had shown a partial virologic response to prior treatment, SVR rates were 59%, 54%, and 15%, respectively. For those with no virologic response to prior treatment (null responders), SVR rates were 29%, 33%, and 5%, respectively.

In a trial in approximately 400 treatment-experienced patients conducted by Bacon and colleagues, overall SVR rates were 66% in patients receiving boceprevir and 48 weeks of peginterferon alfa/ribavirin, 59% in those receiving boceprevir with response-guided therapy, and 21% in those receiving standard peginterferon alfa/ribavirin.6 SVR rates were 75%, 69%, and 29%, respectively, among patients who had relapsed after prior therapy and 52%, 40%, and 7%, respectively, among those who had partial response to prior treatment.

Increased Toxic Effects With Addition of Telaprevir or Boceprevir

Jacobson and colleagues reported that adverse events occurred more frequently in telaprevir-containing study arms than in the peginterferon alfa/ribavirin alone arm. Adverse effects included pruritus (45%-50% with telaprevir vs 36% with peginterferon alfa/ribavirin), nausea (40%-43% vs 31%), rash (35%-37% vs 24%), anemia (37%-39% vs 19%), and diarrhea (28%-32% vs 22%). In the boceprevir trial conducted by Poordad and colleagues, anemia (49% in the boceprevir group vs 29% in standard treatment group) and dysgeusia (37%-43% vs 18%, respectively) were more common in boceprevircontaining study arms.

Resistance to HCV Protease Inhibitors

Because neither interferon alfa nor ribavirin is a direct-acting antiviral agent, viral resistance is a new phenomenon in HCV treatment. Resistance to the protease inhibitors (PIs) telaprevir and boceprevir is detected in approximately 50% of patients in whom therapy containing these agents fails.7,8 To date, there is no evidence that resistant variants have greater replicative fitness or pathogenicity than wild-type virus. As has been observed with HIV, there is a return to predominance of wild-type virus generally within 18 months of stopping HCV PI treatment.9 However, unlike HIV, there is no biologic basis for archiving of PI-resistant variants in the body.

Table 1. Sustained Virologic Response Rates According to Patient and Disease Characteristics in Treatment-Naive Patients Receiving Telaprevir or Boceprevir plus Peginterferon Alfa/Ribavirin Compared with Peginterferon Alfa/Ribavirin Alone

TPV 12 indicates patients receiving telaprevir for 12 weeks; Peg/RBV 24-48, peginterferon alfa and ribavirin for 24 to 48 weeks; Peg/RBV 48, peginterferon alfa and ribavirin for 48 weeks; BOC 44, boceprevir for 44 weeks. Adapted from Jacobson et al2 and Poordad et al.4

The long-term consequences of selecting for HCV PI resistance are unclear at this time. Investigations are currently underway on whether emergence of resistance will result in poorer response to subsequent treatment containing a PI. There are no convincing data thus far that baseline resistance to HCV PIs affects response to treatment. Thus, although there is a commercially available assay for testing for HCV resistance, for now there is no indication for testing to guide immediate treatment decisions. However, it may be prudent to document resistant variants in case the information becomes useful in the future.

More Potent Therapy Reduces Predictive Value of Some Risk Factors for Poor Response

More potent anti-HCV therapy reduces the value of some of the traditional factors predictive of poor response to peginterferon alfa/ribavirin therapy. This is a good thing, however, because the loss of predictive value is the result of higher cure rates in subgroups of patients with traditionally greater risk of poor response. Most notable is the diminished effect of higher HCV viral load in predicting poorer treatment outcome with peginterferon alfa/ribavirin (see Table 1). For example, in the pivotal telaprevir trial, SVR rates were similar among telaprevir-receiving patients with baseline HCV RNA viral load 800,000 IU/mL or higher and those with viral load less than 800,000 IU/mL (74% and 78%, respectively).2 The SVR rate in those with elevated viral load receiving telaprevir represents a striking improvement over the response rate among patients with high viral load receiving peginterferon alfa/ ribavirin alone (36%). In the pivotal boceprevir trial, the SVR rate among boceprevir recipients with elevated baseline viral load was 63%, compared with 33% among patients with elevated baseline viral load receiving peginterferon alfa/ribavirin alone.4

As noted previously, black race is also a risk factor for poorer response to peginterferon alfa/ribavirin. The difference in the frequency of the unfavorable interleukin-28B genotype explains about half of the difference in treatment response between black and nonblack patients. Although there was still a difference in SVR rates between black patients and white patients receiving telaprevir (62% and 75%, respectively), the SVR rate in black patients represents a striking improvement over that achieved with peginterferon alfa/ribavirin alone (25%).2 Similarly, black patients receiving boceprevir had a lower SVR rate than white patients, but the high cure rate in black patients receiving boceprevir compared with those receiving peginterferon alfa/ribavirin alone is another striking improvement—53% versus 23%, respectively.4 Some of the differences observed between the telaprevir and boceprevir studies, with regard to response rates in patient subgroups, likely reflect the fact that the post hoc analyses were performed in different patient populations.

Comparison of Telaprevirand Boceprevir-Containing Regimens

Table 2 provides an overview of characteristics of HCV treatment with telaprevir- and boceprevir-containing regimens. A 4-week lead-in period with peginterferon alfa/ribavirin is recommended before adding boceprevir and no lead-in is recommended for patients receiving telaprevir,8,10 reflecting the way the drugs were developed in phase II and, especially, phase III studies. Boceprevir is administered for 24 weeks or 44 weeks in treatment-naive patients and for 32 weeks or 44 weeks in treatment-experienced patients, depending on early virologic response, whereas telaprevir is administered for 12 weeks in both treatment-naive and treatment–experienced patients.

Table 2. Selected Characteristics of Boceprevir and Telaprevir

*RGT indicates response-guided therapy; PI, protease inhibitor; eRVR, early rapid virologic response. RGT is not recommended in patients with cirrhosis or HIV coinfection.

Response-guided therapy is not recommended in patients with cirrhosis or in HIV-coinfected patients. Responseguided therapy in HIV-seronegative, noncirrhotic, treatment-naive patients is permitted based on an HCV RNAnegative response during weeks 8 to 24 with boceprevir treatment and at weeks 4 and 12 with telaprevir treatment. Based on clinical trial data, it is estimated that 44% of treatment-naive patients receiving boceprevir and 58% to 65% of treatment-naive patients receiving telaprevir are eligible for response-guided therapy. The total duration of anti-HCV treatment in treatment- naive patients, depending on presence or absence of early virologic response, is 28 weeks or 48 weeks for boceprevir, and 24 weeks or 48 weeks for telaprevir.

Response-guided therapy in treatment- experienced patients is not recommended for patients receiving boceprevir who were null responders to prior treatment or for patients receiving telaprevir who were partial or null responders. For treatment-experienced patients receiving boceprevir, total anti-HCV treatment duration is 36 weeks (for those with eRVR) or 48 weeks. Total treatment duration is 24 weeks or 48 weeks for patients receiving telaprevir. Anti-HCV therapy with boceprevir should be stopped due to futility if HCV RNA level is greater than 100 IU/mL at week 12 or if there is detectable HCV RNA at week 24. The recommended stopping rule for telaprevir- containing therapy is a viral load of greater than 1000 IU/mL at week 4 or 12, or detectable virus at week 24.

As noted previously, there are added adverse effects with the addition of either of the PIs to peginterferon alfa/ ribavirin. There is an increased risk of anemia with boceprevir compared with peginterferon alfa/ribavirin therapy alone, and telaprevir is associated with increased risk of anemia and skin and gastrointestinal side effects. Pill burdens differ between the two treatments, with boceprevir requiring four 200 mg pills every 8 hours and telaprevir requiring two 375 mg pills every 8 hours. There is also a difference in food requirements: boceprevir needs to be taken with some food, whereas each dose of telaprevir needs to be taken with a meal containing at least 20 g of fat.

The addition of a new agent to HCV treatment regimens increases cost as well as cure rates. A 48-week course of peginterferon alfa/ribavirin costs approximately $38,000. Full courses of telaprevir (12 weeks) and boceprevir (up to 44 weeks) cost approximately $50,000.

Ongoing Studies of HCV PIs

Patients with HCV infection in whom PI treatment has yet to be fully evaluated are those with more advanced disease (eg, patients with decompensated cirrhosis and transplant patients), those with HBV coinfection, and those with HIV coinfection. In addition, safety and efficacy of these drugs have not been established in patients with HCV genotype 2 or 3 infection. Genotype 2 infection is responsive to peginterferon alfa/ribavirin in most patients, and there is some indication that cure rates are improved with the addition of a PI. Genotype 3 infection is more difficult to treat in many cases, and there is some evidence indicating that response rates are not improved with the addition of a PI.

Studies in HIV Coinfection

In a small study by Sulkowski and colleagues, patients with HCV/HIV coinfection received a full 48-week course of anti-HCV therapy with telaprevir plus peginterferon alfa/ribavirin or peginterferon alfa/ribavirin alone with or without antiretroviral therapy.11 The group receiving peginterferon alfa/ribavirin without antiretroviral therapy included patients with high CD4+ cell counts who did not meet current guidelines for initiation of antiretroviral therapy. Patients who received antiretroviral therapy took efavirenz/tenofovir/emtricitabine, or ritonavir-boosted atazanavir with tenofovir/emtricitabine or tenofovir/lamivudine. Patients who received the efavirenz-containing regimen received an additional telaprevir pill with each dose to compensate for lowered blood levels due to pharmacokinetic interaction with efavirenz. As shown in Figure 1, the telaprevir-containing regimen markedly improved week 4 and week 12 virologic responses in patients receiving and not receiving antiretroviral therapy. These promising findings need to be confirmed in larger studies.

Figure 1. Hepatitis C virus (HCV) virologic responses to telaprevir-containing therapy at week 4 (left) and week 12 (right) in patients with HCV/HIV coinfection, according to antiretroviral regimen. Numerals in bars show total number of patients in treatment group. EFV indicates efavirenz/tenofovir/emtricitabine; ATV/r, ritonavir-boosted atazanavir with tenofovir/emtricitabine or tenofovir/lamivudine. Adapted from Sulkowski et al.11

A phase II trial of boceprevir with peginterferon alfa/ribavirin in HIV/ HCV-coinfected patients is ongoing. A total of 99 coinfected patients with stable HIV disease are being treated with a lead-in of 4 weeks of peginterferon alfa plus weight-based ribavirin, then randomly assigned to add boceprevir (800 mg every 7-9 hours) or placebo for an additional 44 weeks. Subjects were allowed into the study if they were on raltegravir or ritonavirboosted PIs. Baseline HCV RNA level was above 800,000 IU/mL for 88% of subjects; 82% were white, and 5% had cirrhosis.12

The proportion of patients with undetectable HCV RNA at week 8 was higher in the group receiving boceprevir (24 of 64 [37.5%] with undetectable HCV RNA) than in the group receiving placebo (5 of 34 [14.7%]). At week 24, HCV RNA was undetectable in 43 of 61 patients (70.5%) in the boceprevir arm and undetectable in 11 of 32 (34.4%) in the placebo arm. Treatment was discontinued in 3 (9%) and 9 (14%) of the patients in the placebo and boceprevir arms, respectively, because of adverse events.

Updates on the trials described above were presented at the 19th Conference on Retroviruses and Opportunistic Infections in March 2012. In the telaprevir trial in HIV/HCV-coinfected patients, 28 of 38 patients (74%) receiving telaprevir plus peginterferon alfa/ribavirin had undetectable levels of HCV RNA at week 24 (end of treatment), compared with 12 of 22 patients (55%) in the peginterferon alfa/ribavirin–only control group.13 Twelve weeks after stopping therapy, all 28 of the 38 (74%) who had undetectable levels of HCV RNA at the end of telaprevir treatment had sustained virologic response. In the control group, 10 of 22 patients (45%) had sustained virologic response.

In the boceprevir trial, 39 of 61 coinfected patients (63.9%) receiving boceprevir plus peginterferon alfa/ribavirin had undetectable HCV RNA at week 48 (end of treatment), compared with 10 of 34 (29.4%) receiving peginterferon/ alfa alone.14 Twelve weeks after stopping therapy, 37 of 61 patients (60.7%) who had received boceprevir had sustained virologic response, compared with 9 of 34 (26.5%) in the peginterferon alfa/ribavirin–only group.

These results in coinfected patients are notable because in both studies, virologic response was substantially better than with interferon alfa/ribavirin alone. Virologic response rates were also nearly as high as those in monoinfected patients.

Potential for Cure Without Interferon Alfa

Peginterferon alfa therapy is associated with considerable toxicity, and there is intense interest in developing treatments that would spare patients from the rigors of such therapy. An example of studies assessing this possibility was reported by Lok and colleagues.15 Patients who were prior null responders to peginterferon alfa/ribavirin therapy received a combination of an HCV PI and an HCV nonstructural protein 5A (NS5A) inhibitor (which is active at different steps of the viral replication process than PIs), with or without peginterferon alfa/ribavirin.

Four of 11 patients receiving the PI and NS5A inhibitors without peginterferon alfa/ribavirin had viral loads that fell below the limit of quantitation at week 12 and remained undetectable after stopping therapy, showing in principle that cure is achievable without interferon alfa therapy. Six of the 11 patients exhibited viral breakthrough. It is also noteworthy that all 10 patients receiving the 2 direct-acting antivirals in combination with peginterferon alfa/ribavirin had undetectable virus at week 12, a remarkable outcome of treatment in prior null responders. There is considerable excitement over what might be achieved with multidrug combinations of the numerous investigational direct-acting agents.

Although formal guidelines for treatment of HIV/HCV-coinfected persons are being planned, at this time treatment should be prioritized for those with advanced liver fibrosis (cirrhosis and bridging fibrosis). When possible, coinfected patients should be enrolled in clinical trials to expand the available information on optimal HCV treatments in that setting.

Summary

The current era in HCV treatment is reminiscent of the transformation of HIV treatment that occurred in the mid-1990s. With the new HCV treatments, cure and complications occur more frequently. We can make smart applications of the treatments available to us right now in some patients, and we await tomorrow’s treatments for other patients. As with the first wave of HIV medications in the potent antiretroviral era, the new HCV drugs offer huge advantages but also present substantial challenges.

Presented by Dr Thomas in October 2011. First draft prepared from transcripts by Matthew Stenger. Reviewed and edited by Dr Thomas in February 2012.

Dr Thomas has received grants and research support from Gilead Sciences, Inc, and Merck & Co, Inc. He has served as a consultant to Merck & Co, Inc.

References

1. Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

2. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416.

3. Sherman KE, Flamm SL, Afdhal NH, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365:1014-1024.

4. Poordad F, McCone J, Jr., Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206.

5. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417-2428.

6. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207-1217.

7. Vierling JM, Kwo PY, Lawitz E, et al. Frequencies of resistance-associated amino acid variants following combination treatment with boceprevir plus PEGINTRON (peginterferon alfa-2b)/ribavirin in patients with chronic hepatitis C (CHC), genotype 1 (G1). Hepatology. 2010;52(Suppl S1):702A-703A.

8. Telaprevir [package insert]. Cambridge, MA: Vertex Pharmaceuticals; 2011.

9. Zeuzem S, Sulkowski M, Zoulim F, et al. Long-term follow-up of patients with chronic hepatitis C treated with telaprevir in combination with peginterferon alfa- 2a and ribavirin: interim analysis of the Extend study. Hepatology. 2010;52(Suppl S1):436A.

10. Boceprevir [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2011.

11. Sulkowski M, Dieterich D, Sherman K, et al. Interim analysis of a phase 2a doubleblind study of TVR in combination with pegIFN-alfa2a and RBV in HIV/HCV coinfected patients. [Abstract 146LB.] 18th Conference on Retroviruses and Op- portunistic Infections (CROI). February 27-March 2, 2011; Boston, MA.

12. Sulkowski M, Pol S, Cooper C, et al. Boceprevir plus peginterferon/ribavirin for the treatment of HCV/HIV co-infected patients: interim on-treatment results. [Abstract LB-37.] 49th Annual Meeting of the Infectious Diseases Society of America (IDSA). October 20-23, 2011; Boston, MA.

13. Dieterich D, Soriano V, Sherman K, et al. Telaprevir in combination with pegylated ininterferon- a-2a+RBV in HCV/HIV-co-infected patients: a 24-week treatment interim analysis. [Abstract 46.] 19th Conference on Retroviruses and Opportunistic Infections (CROI). March 5-8, 2012; Seattle, WA.

14. Sulkowski M, Pol S, Cooper C, et al. Boceprevir + pegylated interferon + ribavirin for the treatment of HCV/HIV-co-infected patients: end of treatment (week-48) interim results. [Abstract 47.] Proceedings from the 19th Conference on Retroviruses and Opportunistic infections (CROI). March 5-8, 2012; Seattle, WA. 15. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216-224.

Source

Addressing Disparities, Promoting Health Equity and Ending HIV/AIDS

Jeffrey Levi

Executive Director, Trust for America's Health; Chair of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Posted: 04/27/2012 1:54 pm

While we have made incredible strides in addressing HIV/AIDS over the past 30 years, the disease remains devastatingly prevalent in America, especially among gay and bisexual men. This population accounts for 57 percent of new HIV infections and a gay man who is 18 years old faces a two in five chance of becoming infected with HIV by the time he is 40, as noted by a Trust for America's Health (TFAH) issue brief. In 2009, the estimated rates of new HIV infections among black men and Latino men were 6.5 times and 2.5 times as high, respectively, as that of their white counterparts. Disparities are most severe among young black gay and bisexual men.

The National HIV/AIDS Strategy (NHAS) provides a roadmap for national efforts to end the HIV/AIDS epidemic. The primary goals of the NHAS are to reduce HIV incidence, increase access to care, optimize health outcomes and reduce HIV-related health disparities. The NHAS describes priority areas in need of interventions, outlines steps for a coordinated national response to the HIV epidemic and identifies measurable outcomes. This strategy reinforces the importance of focusing efforts on those at greatest risk, and is paramount in addressing the prevalence of HIV/AIDS among gay and bisexual men, particularly among racial and ethnic minorities.

A critical step in achieving the goals of the National AIDS Strategy is increasing awareness of HIV status (or "serostatus") among gay and bisexual men. Almost 50 percent of HIV transmissions come from the 20 percent of HIV-positive individuals who are unaware of their status. Promoting HIV testing and early linkage to care helps suppress viral load, reinforces less risky behavior, and helps prevent the transmission of HIV.

Increasing knowledge of serostatus requires routine HIV testing in the clinical setting, which can be accomplished through changes to guidelines and reimbursements. This is incredibly important because most individuals who do not know their status have actually had a recent interaction with the health care system but, unfortunately, were not tested. In order to reach the highest-risk populations, including racial and ethnic minorities, there is a need to train providers on testing and creating culturally competent approaches to gay men's health in general.

Representative Maxine Waters recently introduced important legislation that would promote increased HIV testing by removing cost as an obstacle. The Waters bill, Routine HIV Screening Coverage Act of 2012 (HR4470), would require all individual, group and federal employee health insurance plans to reimburse for HIV testing. This bill would be a significant step toward encouraging those who are unaware of their status to get tested.

As noted by the NHAS, HIV testing is just one piece of a comprehensive set of services that are needed to end the HIV epidemic. Expanded knowledge of serostatus must be complemented by a supportive environment for the gay and bisexual community. HIV prevention and treatment efforts, especially for racial and ethnic minorities, can be compromised by stigma and the social determinants of health, including access to stable housing, education, health care, and other key resources. Resources must be provided to mobilize the gay and bisexual community and promote gay men's health at the national, state and local level.

We've come a long way in the battle against HIV/AIDS. However, we must remain vigilant: We cannot ignore the startling statistics of new HIV infections of gay and bisexual men, especially among black and Hispanic men. By pursuing the comprehensive approach to prevention and treatment outlined in the National HIV/AIDS Strategy, we can begin to end the HIV/AIDS epidemic.

Trust for America's Health is proudly taking part in the Health Equity Can't Wait! blog carnival celebrating National Minority Health Month. Participating bloggers are health, consumer, civil rights, and provider advocates committed to promoting health equity. You can find all the posts for the carnival here.

For more by Jeffrey Levi, click here.

For more on HIV/AIDS, click here.

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Immediate versus delayed treatment in patients with acute hepatitis C based on IL28B polymorphism: a model-based analysis

J Hepatol. 2012 Apr 17. [Epub ahead of print]

Deuffic-Burban S, Castel H, Wiegand J, Manns MP, Wedemeyer H, Mathurin P, Yazdanpanah Y.

Inserm ATIP-AVENIR "Modélisation, aide à la décision et coût-efficacité en maladies infectieuses", Lille/Paris, France; EA2694, Université Lille Nord de France, Lille, France.

Abstract

BACKGROUND AND AIMS:

Timing of treatment initiation in acute hepatitis C (AHC) patients is unclear. Spontaneous viral clearance argues for a "watch-and-wait" strategy. However, early initiation of treatment could increase the sustained virological response (SVR) rate. We compared 3 different HCV treatment initiation strategies in patients with AHC according to presence of clinical symptoms and IL28B polymorphism: (1) within 2 months after transmission (immediate initiation), (2) at 3 months (early initiation); (3) at 4/5 months (delayed initiation).

METHODS:

We calculated spontaneous HCV clearance probability based on symptomatic (sAHC) and asymptomatic (aAHC) nature of disease and C/C or non-C/C genotype. We used different SVR probabilities according to delay between transmission and treatment. We estimated the probability of developing chronic hepatitis C (CHC).

RESULTS:

The probability of developing CHC was lower for immediate treatment initiation (7.1% in C/C and 7.3% in non-C/C patients with sAHC; 6.6% in C/C and 7.1% in non-C/C patients with aAHC) than for delayed initiation (13.5% in C/C and 18.0% in non-C/C patients with sAHC; 14.6% in C/C and v in non-C/C patients with aAHC) regardless of the presence of symptoms or IL28B genotype.

CONCLUSIONS:

In patients such as health care workers in whom HCV is detected <2 months following transmission, treatment should be immediately initiated regardless of clinical symptoms and IL28B polymorphism. In those in whom HCV is detected >2 months after transmission, treatment 4/5 months after may be preferable because of a higher rate of spontaneous HCV clearance after 2 months and poor HCV treatment efficacy's differential between months 3 and 4/5.

Copyright © 2012. Published by Elsevier B.V.

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National patterns and predictors of liver biopsy use for managing hepatitis C

J Hepatol. 2012 Apr 17. [Epub ahead of print]

Groessl EJ, Liu L, Ho SB, Kanwal F, Gifford AL, Asch SM.

VA San Diego Healthcare System; University of California San Diego.

Abstract

BACKGROUND & AIMS:

Liver biopsy remains the standard, recommended method for assessing liver damage associated with chronic hepatitis C (HCV) infection. However, there is considerable debate about how liver biopsy should best be used, especially with the advent of more efficacious antiviral therapies. To identify the factors that influence the use of liver biopsy for HCV patients, we describe variations in liver biopsy use at the delivery system and patient level in a national VA sample.

METHODS:

We analyzed VA HCV registry data for 171,893 VA patients with confirmed chronic HCV. Delivery system characteristics included geographic region and specialist time. Patient characteristics included antiviral treatment indicators, contraindications, volume of healthcare visits, and demographic variables. Logistic regression was used to explore correlates of biopsy use.

RESULTS:

Liver biopsy use in the VA system increased from 1997-2003 but began declining in 2004. Rates of liver biopsy from 2004-06 varied by VA region, ranging from 5 to 18%. Treatment contraindications and laboratory tests were significantly associated with more biopsies. Demographic variables (higher age, lower BMI, race/ethnicity, and less % service connected disability) were associated with fewer biopsies. Regional variability remained significant independent of volume of care and specialist time.

CONCLUSIONS:

Liver biopsy rates in the VA system have variability that seems unrelated to clinical need. New antiviral therapies and non-invasive assessment techniques may create additional uncertainty for the role of liver biopsy, perhaps explaining its decline in recent years. The availability of more effective antiviral therapies may also affect biopsy rates in the future.

Copyright © 2012. Published by Elsevier B.V.

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Integrated Treatment of Persons with Co-Occuring HCV & Alcohol Use

HEP ART

For those infected with Hepatitis C (HCV), alcohol use has a direct negative impact on the liver, increasing the risk and progression of liver fibrosis and hepatocellular carcinoma, which can lead to liver failure and death. Few studies have systematically examined effective approaches to address co-occurring HCV and alcohol use. Integrated Behavioral Health-Medical models have demonstrated decreases in alcohol use in primary care settings, but have rarely been tested in HCV specialty care settings. Data on integrated models for African American patients with HCV are lacking. Medical providers need data on effective treatments for the spectrum of problem drinking with which their HCV-infected patients present.

Principal Investigator, Andrew Muir, MD, MHS, and Rae Jean Proeschold-Bell, PhD were awarded R21 funding from the National Institutes of Alcohol Abuse and Alcoholism to test the feasibility of implementing an integrated treatment model among persons with HCV and problem drinking ranging from hazardous consumption to harmful alcohol use. They examined a) the feasibility of adapting an integrated intervention designed for alcohol-using HIV populations to an HCV population; b) the impact of this intervention on participation in alcohol treatment, changes in alcohol use, and participation in HCV medical care; and c) the factors associated with outcomes in this sample.

Sixty participants were enrolled in the Integrated Alcohol-HCV treatment model provided at an HCV medical clinic. Outcome variables were assessed pre-, during, and post-intervention. The results from the study, including a 44% alcohol abstinence rate, indicated success. An R01 proposal to employ a Randomized Controlled Trial (RCT) design to test the integrated model’s effectiveness was submitted in June 2011.

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Also See: Integrated Health Care Model Shows Promise for Hepatitis C Patients in Durham

EASL 2012: Interferon Lambda Beats Alfa in Clearing HCV Genotype 2 or 3

From Medscape Medical News

Daniel M. Keller, PhD

April 27, 2012 (Barcelona, Spain) — In a phase 2b study of treatment-naive adults with chronic hepatitis C virus (HCV) infection, pegylated interferon-lambda was more effective and safer than interferon-alfa in eliminating the virus in patients infected with HCV genotypes 2 or 3. The study is the first report of sustained virologic response with lambda.

Stefan Zeuzem, MD, professor of medicine and chief of the Department of Medicine I at the J.W. Goethe University Hospital in Frankfurt, Germany, who presented the results here at the International Liver Congress 2012, showed data demonstrating that 180 μg of lambda, compared with alfa, produced a more rapid virologic response and a greater sustained virologic response at 24 weeks (SVR24), and was associated with fewer adverse events and less need for a dose reduction of lambda and of the accompanying ribavirin.

Treatment of chronic HCV with alfa interferons and ribavirin is limited by hematologic toxicity and other adverse effects. Lambda has marked activity against HCV and a restricted distribution of receptors in the body, which could make organ systems outside the liver less susceptible to its effects.

Dr. Zeuzem and colleagues performed a blinded randomized study of 526 noncirrhotic treatment-naive HCV-infected adults, 18 to 70 years of age, 118 of whom were chronically infected with genotype 2 or 3 and had HCV RNA levels of at least 100,000 IU/mL. The genotype 2/3 patients received daily ribavirin and weekly doses of lambda 120 μg (n = 29), 180 μg (n = 29), or 240 μg (n = 30) for 24 weeks. Other patients (n = 30) received daily ribavirin plus alfa 180 μg weekly for 24 weeks.

At baseline, the 4 groups were similar in age (range, 48.1 to 50.6 years), sex (range, 52% to 70% male), body mass index (range, 27.8 to 29.0 kg/m²), and viral load (range, 6.42 to 6.66 log₁₀ IU/mL). Most participants were white (range, 76.7% to 89.7%). The proportion of genotype 2 patients was 41.4% in the 120 μg group, 58.6% in the 180 μg group, 53.3% in the 240 μg group, and 50% in the alfa group. A large majority of patients in each group had low liver fibrosis scores.

Lambda Effective With Fewer Adverse Events

Lambda/ribavirin treatment was associated with an early and rapid drop in HCV RNA in a dose-dependent manner. After 2 weeks of treatment, the greatest reductions were seen with the 180 μg and 240 μg doses. All 3 doses of lambda produced more rapid decreases in virus level than alfa/ribavirin. The 180 μg dose will be used going forward in phase 3 trials.

HCV RNA was undetectable at week 4 in 75.9% of patients in the 180 μg group and in 30.0% in the alfa group (P < .05). Complete early virologic response (meaning HVC RNA was detectable at week 4 but not at week 12) and SVR24 were somewhat better with lambda than with alfa, but the difference was not statistically significance. In the lambda groups, 96.6% of patients achieved a complete early virologic response and 75.9% achieved SVR24.

With lambda 180 μg, 70.6% of genotype 2 patients achieved SVR24, as did 83.3% of genotype 3 patients.

Relapse rates, defined as an HCV RNA level of 25 IU/mL or greater during the follow-up period, were low, at about 21% in the lambda 180 μg group and about 25% in the alfa group.

Although all groups experienced a high level of adverse events (in the range of about 95%), some long associated with alfa therapy — "in particular, flu-like symptoms...such as myalgia, arthralgia, pyrexia, and chills" — were significantly lower in the lambda groups (7% to 17% in the 180 μg group) than in the alfa group (20% to 33%). Flu-like symptoms were definitely lower in all 3 lambda groups (20.7% for 180 μg) than in the alfa group (40%), Dr. Zeuzem said, as were musculoskeletal symptoms (20.7% vs 63.3%).

However, the prevalence of psychiatric adverse events (e.g., depression, irritability, or insomnia) was greater in the lambda groups than in the alfa group (41.4% vs 33.3%).

There were no discontinuations because of adverse events in the 180 μg group, but 6.7% dropped out of the alfa group. In the lambda groups, there were dose reductions in lambda or ribavirin at a rate of 6.9% for each; in the alfa group, there were dose reductions at rates of 26.7% for alfa and 43.3% for ribavirin.

Serious adverse events affected less than 4% of patients in the 180 μg and alfa groups. There were no serious adverse events directly related to treatment in the lambda groups.

It has been reported that lambda causes elevations in serum bilirubin, but in this trial at the 180 μg dose, there was only 1 patient (3.4%) with bilirubin elevation (in the range of 1.6 to 2.5 times the upper limit of normal).

There were no reductions in neutrophil or platelet counts associated with any dose of lambda. There were drops in both in the alfa group as long as therapy continued. Low hemoglobin (below 10 g/dL, or a drop of at least 3.4 g/dL), often associated with alfa/ribavirin, occurred in 44.8% of the alfa group and necessitated a ribavirin dose reduction in 23.3% of patients. Hemoglobin levels did not drop as much in the 180 μg group; only 6.9% were classified as having low hemoglobin, and none required a ribavirin dose reduction.

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University and Hippokration General Hospital in Greece, and a member of the Governing Board Scientific Committee of the European Association for the Study of the Liver (EASL), summarized the findings for Medscape Medical News.

"It seems that the efficacy of interferon lambda might be slightly higher [than alfa], but definitely we can say that the safety profile is better.... The only side effect that was higher, and we cannot explain that, is the psychiatric side effects," he said.

In light of a robust pipeline of oral drugs now in development, Dr. Papatheodoridis said the use of interferons could be fairly limited in the treatment of HCV in the future. "I don't know what role interferon lambda may find when and if it gets licensed. After 2 or 3 years, it is possible that most of the patients will be treated with interferon-free regimens," he explained.

Mark Thursz, MD, professor of hepatology in the Department of Medicine at Imperial College, London, United Kingdom, and secretary general of the EASL, alluded to this point during a news conference, drawing attention to the safety profile of lambda. Patients receiving ribavirin typically show a drop in hemoglobin, "but there's a smaller drop...in the lambda- than in the alfa-treated patients," he said. "More important are these data on neutrophils and platelets.... You can see no drop in patients who were treated with the lambda interferon.... For patients who still need an interferon and in whom problems with cell counts are going to be an issue, this is a solution."

Dr. Papatheodoridis noted that the bilirubin increase seen with lambda probably does not indicate any damage to the liver, but is perhaps the effect of "this interferon on the enzymes that are involved in the metabolism of bilirubin, which is not very dangerous; it's a lab finding without major clinical significance."

Dr. Zeuzem reports being a consultant for Abbott, Achillion, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Idenix, Inhibitex, iTherX, Janssen, Merck, Novartis, Presidio Pharmaceuticals, Roche, Santaris, and Vertx Pharmaceuticals. Dr. Papatheodoridis and Dr. Thursz have disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 10. Presented April 19, 2012.

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Breast-Feeding Past 6 Months Lowers Risk for HIV Transmission

From Medscape Medical News

Ricki Lewis, PhD

April 27, 2012 — Breast-feeding beyond 6 months when mother or infant is taking antiretrovirals (ARVs) can prevent HIV transmission, according to results from the Breastfeeding, Antiretrovirals, and Nutrition (BAN) trial published online April 26 in The Lancet.

Before 2010, the World Health Organization (WHO) and other public health agencies recommended ceasing breast-feeding for HIV-positive mothers in resource-poor countries at or before 6 months to balance the benefits of breast-feeding with the risk of transmitting HIV in milk. However, the newly reported BAN results indicate that once breast-feeding ceases at 6 months, risk for HIV transmission actually increases. In response to this and other studies, WHO guidelines now recommend that HIV-infected mothers of uninfected infants breast-feed for the first year.

Denise J. Jamieson, MD, from the US Centers for Disease Control and Prevention in Atlanta, and the BAN study team randomly assigned mother-infant pairs in Malawi to 3 groups: maternal triple ARVs, infant nevirapine, or no extended postnatal ARVs (controls). Infants were tested for HIV at birth and 2, 12, 28, and 48 weeks. Those infected by 2 weeks were released from the study and treated, as were mothers who progressed to AIDS or had plunging T-cell counts.

Women were instructed to wean between 24 and 28 weeks. At 32 weeks, most of the women in the intervention groups (96%) and in the control group (88%) reported having ceased breast-feeding.

As expected, at 28 weeks, pairs in which 1 member received ARVs had lower incidence of HIV infection than controls. Of the 676 mother-infant pairs in which the mothers took ARVs, 30 infants contracted HIV between 2 and 48 weeks. Of the 680 mother-infant pairs in which infants took nevirapine daily, 25 infants became infected. Of the 542 controls, 38 infants became infected.

"The cumulative risk of HIV-1 transmission by 48 weeks was significantly higher in the control group (7%, 95% CI [confidence interval] 5-9) than in the maternal-antiretroviral (4%, 3-6 p=0.0273) or the infant-nevirapine (4%, 2-5; p=0.0027) groups," the researchers write.

The research team collected data from 2004 to 2010. In 2008, noting the increased rate of HIV transmission in the controls, a data safety monitoring board at the National Institute of Allergy and Infectious Diseases recommended that all participants be assigned to an intervention group.

Assessing HIV infection after 28 weeks, when breast-feeding stopped, was revealing: 30% of the infections occurred during that period. Nine were in the maternal-ARV group, 13 in the infant-nevirapine group, and 6 in the control group.

Moreover, adverse events were more frequent during the postweaning period from 29 to 48 weeks, including diarrhea, impaired growth, malaria, tuberculosis, and death.

"The finding that mortality after 28 weeks was significantly higher than before this point (0.120 vs 0.065 per 100 person-weeks; p=0.0070) is cause for grave concern, because mortality rates should decrease with infant age," write Louise Kuhn, MD, Gertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, and Hoosen M. Coovadia, MD, University of Witwatersrand, Johannesburg, South Africa, and University of KwaZulu-Natal, Durban, South Africa, in an accompanying editorial.

A limitation of the study was the inability to draw conclusions about increased risk for adverse events in infants aged 6 to 12 months without also considering a group that continues breast-feeding.

Despite that limitation, Dr. Kuhn and Dr. Coovadia conclude that "[e]arly weaning is neither effective nor safe as an HIV prevention strategy."

Two coauthors received lecture fees from Abbott Laboratories. Another coauthor received free diagnostic kits from Abbott, Roche, Gen-Probe, IQuum, and Perkin-Elmer. The University of North Carolina received grant support from Abbott and GlaxoSmithKline. Dr. Kuhn and Dr. Coovadia have disclosed no relevant financial relationships.

Lancet. Published online April 26, 2012. Abstract Editorial

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Bipolar patients can safely and successfully receive interferon-based hepatitis C antiviral treatment

Eur J Gastroenterol Hepatol. 2012 Apr 8. [Epub ahead of print]

Kelly EM, Corace K, Emery J, Cooper CL.

Department of Medicine, The Ottawa Hospital Division of Infectious Diseases Viral Hepatitis Program, University of Ottawa, Ottawa, Canada.

Abstract

AIM:

Patients with bipolar disease are often not considered for hepatitis C virus (HCV) antiviral treatment and are excluded from clinical trials because of the risk of interferon-induced exacerbation of their underlying mood disorder. As this risk has not been well quantified in bipolar patients, we evaluated the safety and efficacy of HCV treatment in this population.

METHODS:

A retrospective analysis of HCV patients evaluated at The Ottawa Hospital between January 2000 and February 2008 (n=910) was carried out. Information on demographics, psychiatric history and treatment, baseline liver biopsy and blood work, treatment initiation, adherence, and therapeutic outcomes was collected. This was compared between bipolar patients (B), those with a history of depression (D), and those with no mental health disorders (N).

RESULTS:

Of 38 bipolar patients (4.2%), 16 (42.1%) initiated HCV treatment, a rate similar to that in patients with a history of depression (41.4%) and in those without psychiatric illness (32.6%). On-treatment psychiatric complications were comparable between the bipolar and depression groups (B=68.8%, D=54.8%; P=0.29) and were higher than in those without psychiatric illness (N=37.1%; P=0.01). Manic episodes were rare. [B=2 (12.5%), D=1 (0.9%), N=1 (0.7%)]. Interferon dose reduction or discontinuation rates for psychiatric complications (B=12.5%, D=7.9%, N=7.4%; P=NS), completion rates (B=50%, D=69%, N=58%), and sustained virologic response rates (genotype 1: B=33%, D=45%, N=49%) were similar between the groups.

CONCLUSION:

Stable bipolar patients have similar rates of on-treatment psychiatric complications as patients with a history of depression. With pharmacologic intervention and close clinical monitoring, well-selected bipolar patients can successfully complete treatment and achieve outcomes comparable to those in nonbipolar patients.

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Hepatitis C virus infects the endothelial cells of the blood-brain barrier

Gastroenterology. 2012 Mar;142(3):634-643.e6. Epub 2011 Dec 1.

Fletcher NF, Wilson GK, Murray J, Hu K, Lewis A, Reynolds GM, Stamataki Z, Meredith LW, Rowe IA, Luo G, Lopez-Ramirez MA, Baumert TF, Weksler B, Couraud PO, Kim KS, Romero IA, Jopling C, Morgello S, Balfe P, McKeating JA.

Hepatitis C Research Group, Institute for Biomedical Research, University of Birmingham, Birmingham, England.

Abstract

BACKGROUND & AIMS:

Hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic syndromes, including central nervous system (CNS) abnormalities. However, it is unclear whether such cognitive abnormalities are a function of systemic disease, impaired hepatic function, or virus infection of the CNS.

METHODS:

We measured levels of HCV RNA and expression of the viral entry receptor in brain tissue samples from 10 infected individuals (and 3 uninfected individuals, as controls) and human brain microvascular endothelial cells by using quantitative polymerase chain reaction and immunochemical and confocal imaging analyses. HCV pseudoparticles and cell culture-derived HCV were used to study the ability of endothelial cells to support viral entry and replication.

RESULTS:

Using quantitative polymerase chain reaction, we detected HCV RNA in brain tissue of infected individuals at significantly lower levels than in liver samples. Brain microvascular endothelia and brain endothelial cells expressed all of the recognized HCV entry receptors. Two independently derived brain endothelial cell lines, hCMEC/D3 and HBMEC, supported HCV entry and replication. These processes were inhibited by antibodies against the entry factors CD81, scavenger receptor BI, and claudin-1; by interferon; and by reagents that inhibit NS3 protease and NS5B polymerase. HCV infection promotes endothelial permeability and cellular apoptosis.

CONCLUSIONS:

Human brain endothelial cells express functional receptors that support HCV entry and replication. Virus infection of the CNS might lead to HCV-associated neuropathologies.

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Hepatitis E: An emerging disease

Rev Med Interne. 2012 Mar 7. [Epub ahead of print]

Bonnet D, Kamar N, Izopet J, Alric L.

Service de médecine interne, fédération digestive, CHU Purpan, place du Docteur-Baylac, TSA 40031, 31059 Toulouse cedex 9, France.

Abstract

The hepatitis E virus is endemic in countries with poor sanitation, where it has many similarities with the hepatitis A virus. It causes a strictly human, feco-oral transmitted, acute, self-limited hepatitis in young adults. The outcome is excellent, except in pregnant women and cirrhotic patients, who experience a high mortality rate. The first cases described in industrialized countries were travellers coming from endemic areas. However, there is now growing evidence that locally-acquired hepatitis E is common in these areas, where it is an emergent disease, despite it is still misdiagnosed. In industrialized countries, hepatitis E spreads sporadically and has a predilection for elderly men with comorbidity, particularly chronic liver diseases. The mortality seems to be higher in this population. In these areas, hepatitis E is due to the genotype 3 virus that is thought to be zoonotically transmitted by pigs and wild boar. Hepatitis E may evolve towards a chronic infection in immunocompromised subjects, particularly in solid organ-transplanted patients. In case of chronic infection, it may cause liver fibrosis and cirrhosis. The diagnosis of hepatitis E is based on serological tests (IgM and IgG) and detection of the viral genome by reverse transcription polymerase chain reaction (RT-PCR) on blood and stools. Acute hepatitis E does not require any treatment but in chronically infected patients, a sustained viral response and finally a definitive viral clearance has been observed after a three-month course of low-dose ribavirin (600 to 800mg/day). Two vaccines underwent successful human trials but are not yet commercially available.

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Social media: how doctors can contribute

The Lancet, Volume 379, Issue 9826, Page 1562, 28 April 2012

doi:10.1016/S0140-6736(12)60658-8

The Lancet

On April 18, The General Medical Council, which regulates medical practice in the UK, opened up its draft guidance on doctors' use of social media for consultation. Comments can be made until June 13, and the results will be published by the end of the year. The guidance emphasises the need to maintain patient confidentiality, provide accurate information, treat colleagues with respect, avoid anonymity online if writing in a professional capacity, be aware of how content is shared, review privacy settings and online presence, declare conflicts of interest, and maintain separate personal and professional profiles.

This conservative approach is not dissimilar to existing guidance from medical associations. Accepting Facebook friend requests from patients is, in general, not advised. But what of situations where doctors and patients are genuine friends? What, too, of the benefits of doctors providing medical information via blogs, Twitter, or Facebook? Current guidance focuses more on the risks than the benefits of doctors' use of social media.

Patients use social networks to research their symptoms, their doctors, their treatments, and to set up support and information groups. Clinicians can use social media to drive awareness, to provide accurate information, and as a portal to communicate with other physicians. An example is the Floating Doctors programme, which uses Facebook and Twitter to ask specialists for clinical advice for patients in remote areas of Central America. Across Africa, the potential for top-quality health information, advice, and access to treatment can be aided by doctors contributing to social media networks. In Taiwan, Facebook use has even contributed to reform of emergency departments.

Much is said about the dangers of social media. Care about posting in a public space is, of course, needed. Doctors, though, should seize the opportunities provided by social networks to improve the health of their patients, and do their utmost to ensure that the highest quality of health information and access to treatment is there for all.

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Integrated Health Care Model Shows Promise for Hepatitis C Patients in Durham

Posted by Anna Both on Apr 26, 2012 in Faculty, Rae Jean Proeschold Bell, Research

Reported by the Duke Global Health Institute:

Four in ten hepatitis C patients who drank alcohol refrained from it as part of a Duke pilot program that integrates alcohol and hepatitis C treatments. Led by DGHI researcher Rae Jean Proeschold-Bell and Duke physician Andrew Muir, the dual model of care may be a viable option for steering these patients away from alcohol, who may otherwise develop serious health complications that lead to liver failure or death.

The Duke study, featured in the April issue of Digestive Diseases and Sciences, involved hepatitis C patients from the Duke Liver Clinic who received both alcohol treatment and medical care over a six-month period. Of the 53 alcohol-drinking patients in the study, 44 percent had stopped drinking alcohol by the end of the six months. Patients who did not become abstinent by six months still reported a 30 percent drop in alcohol consumption, spending on alcohol and urges to drink.

“We were able to show that integrated hepatitis C-alcohol care is feasible,” said Proeschold-Bell, a DGHI faculty member at the Center for Health Policy and Inequalities Research. “More than that, the study shows that such integrated care results in alcohol reductions that benefit patient health.”

Researchers say the intervention worked in part because it focused on liver health, rather than simply reducing alcohol use. It involved weekly group therapy and bi-weekly individual sessions customized to each patient that address alcohol use, nutrition, stress and family support. Because knowledge alone does not change behavior, the addictions specialist taught patients practical ways to improve other aspects of their lives based on their individual circumstances. Study participants were also evaluated for mental illness and had access to a psychiatrist for care, if needed.

The research team also found ways to increase communication and collaboration between the patient’s hepatologist and addictions specialist, a critical part of the study.

“We didn’t know the extent to which we could get busy medical providers and addictions specialists to collaborate. We had to find ways to fit the collaboration into the clinic flow,” said Proeschold-Bell. “In some instances, we had the addictions specialist use a laptop outside the patient exam rooms so medical providers could easily access her and her knowledge about the patient’s alcohol use and behavior changes.”

To date, studies have shown that adults with hepatitis C are three times more likely to have at least one alcoholic drink a day and almost eight times more likely to have at least three drinks a day, compared to adults without hepatitis C. The combination of alcohol use and hepatitis C speeds the time to liver failure and increases rates of liver fibrosis and cancer.

As strong proponents of clinic-based alcohol treatment, Proeschold-Bell and Muir hope to pursue a larger study that recruits patients from the Duke Liver Clinic, the UNC Liver Clinic and the Durham Veterans Affairs Medical Center.

“Alcohol treatment needs to occur in a trusted and known setting,” said Muir. “This study shows that patients will attend alcohol treatment offered in the liver clinic setting and try to change their behaviors in the context of their lives beyond alcohol use.”

More information on this CHPIR project on the HEP ART page

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AHF Urges Swift Passage of Rep. Maxine Waters' "Routine HIV Screening Coverage Act"

PRESS RELEASE

April 26, 2012, 1:41 p.m. EDT

The new bill would require health insurance plans to cover routine HIV tests under the same terms as other routine health screenings. Legislation could spur nationwide compliance with CDC's 2006 HIV testing guidelines recommending HIV testing in routine health settings.

WASHINGTON, Apr 26, 2012 (BUSINESS WIRE) -- AIDS Healthcare Foundation (AHF), the nation's largest HIV/AIDS nonprofit medical provider, today urged Congress to pass Congresswoman Maxine Waters' (D, CA 35th) bill to require health insurance plans to cover routine HIV tests under the same terms and conditions as other routine health screenings. The bill, which is known as the Routine HIV Screening Coverage Act (HR 4470), had been previously introduced by Waters during the 110th and 111th Congress; however, it did not become law.

"The 'Routine HIV Screening Coverage Act' seeks to bring national health policy in line with the science that shows that HIV testing and linkage to treatment is the best way to prevent new infections" said Michael Weinstein, President of AIDS Healthcare Foundation. "By requiring insurer coverage of routine HIV screening, this bill should go a long way in helping to break the chain of new infections by making HIV testing -- and linkage to treatment, far more readily available. We applaud Congresswoman Waters for reintroducing and carrying this lifesaving public health measure."

According to the CDC, approximately 250,000 people with HIV in the United States are unaware of their infection. These so-called "unawares" are estimated to be the source of most new infections. Finding these "unawares" and linking them to AIDS treatment, which has shown to reduce HIV transmission by 96%, would drive down HIV infection rates nationwide.

In 2006, CDC issued guidelines recommending routine HIV testing of adults and adolescents in all health care settings. However, lack of coverage for the cost of providing HIV testing continues to be a key factor in preventing widespread adoption of the CDC guidelines.

"The 2006 CDC guidelines for HIV testing have been largely ignored nationwide because no one knows who will actually cover the costs of such routine screening," said Weinstein. "By requiring health insurance plans to cover routine HIV tests under the same terms as other routine health screenings, Congresswoman Waters' bill should help spur compliance with the CDC's guidelines. The only way to truly get control of HIV in this country is for people to know their status. This step will remove a significant barrier to HIV testing. It is necessary, it is way past time, and Congress should take up and pass this bill immediately."

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 164,000 individuals in 26 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. To learn more about AHF, please visit our website: www.aidshealth.org , find us on Facebook: www.facebook.com/aidshealth and follow us on Twitter: @aidshealthcare

SOURCE: AIDS Healthcare Foundation

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NICE recommends Victrelis and Incivo for hepatitis C

Published: 26/04/2012

Janssen’s Incivo and MSD’s Victrelis have been recommended for reimbursement by the NHS when used in the treatment of hepatitis C.

The National Institute for Health and Clinical Excellence (NICE), which serves as a cost watchdog for England and Wales, has published guidance stating that both treatments should be available for the treatment of genotype 1 chronic hepatitis C, when used in combination with peginterferon alfa and ribavirin.

Professor Carole Longson, health technology evaluationcentre director at NICE, said: “The significant improvement in sustained virological response rates seen with boceprevir or telaprevir plus peginterferon alfa and ribavirin compared with peginterferon alfa and ribavirin alone represents a major benefit for people with genotype 1 chronic hepatitis C.”

Genotype 1 is the most common subtype of hepatitis C in England and Wales affecting around half of the estimated 255,000 people with hepatitis in the region.

It is also the most resistant to treatment, with Longson describing how patients have declined treatment with peginterferon alfa andribavirin alone as the chance for a sustained response was too low to compensate for side effects such as nausea, insomnia, depression and diarrhoea.

Both Incivo and Victrelis work the same way by inhibiting the activity of the NS3/4A serine protease, an enzyme that is essential for viral replication.

NICE said that the serine protease may be partially responsible for the ability of the hepatitis C virus to evade clearance by the host immune system.

The guidance was welcomed by patient group, the Hepatitis C Trust. The organisation’s chief executive Charles Gore said: "People living with genotype-1 hepatitis C who have perhaps been delaying starting treatment, or who have lost hope after their previous treatment had failed them, can now be offered cost effective treatments that offer them a much better chance of clearing the virus than ever before.

“This is really great news and I look forward to direct acting anti-virals being made available to all patients on the NHS as soon as possible."

Source

Hepatitis B and C prevalence among the high risk groups of Pakistani population. A cross sectional study

Published on: 2012-04-26

Hepatitis B and C cause significant morbidity and mortality worldwide. Little is known about the existence of hepatitis B and C among high risk groups of thePakistani population.

The present study was conducted to determine the prevalence of Hepatitis B and C in high risk groups, their comparison and the possible mode of acquisition by obtaining the history of exposure to known risk factors.

Methods: This cross sectional study was carried out in Karachi, from January 2007 to June 2008.HBsAg and Anti HCV screening was carried out in blood samples collected from four vulnerable or at risk groups which included Iinjecting drug users (IDUs), prisoners, security personnel and health care workers (HCWs). Demographic informations was recorded and the possible mode of acquisition was assessed by detailed interview.

Logistic regression analysis was conducted using the STATA software.

Results: We screened 4202 subjects, of these, 681 individuals were reactive either with hepatitis B or C. One hundred and thirty three (3.17%) were hepatitis B reactive and 548 (13.0%) were diagnosed with hepatitis C.

After adjusting for age, security personnel, prisoners and IV drug users were 5, 3 and 6 times more likely to be hepatitis B reactive respectively as compared to the health care workers. IDUs were 46 times more likely to be hepatitis C positive compared withto health care workers.

Conclusion: The prevalence of hepatitis B and C was considerably higher in IDUs, prisoners and security personnel compared to HCWs group.

Hepatitis C is more prevalent than hepatitis B in all these risk groups. Prevalence of hepatitis C increased with the increase in age.

Uses of unsterilized syringes, used syringes, body piercing andillicit sexual relations were found to be important associated risk factors for higher prevalence of Hepatitis B and C in these groups.

Author: Abdul Rauf MemonKashif ShafiqueAshraf MemonAgha Umer DrazMohammad Uzair Abdul RaufSalahuddin Afsar

Credits/Source: Archives of Public Health 2012, 70:9

Source

FDA Drug Safety Communication: Updated information on drug interactions between Victrelis (boceprevir) and certain boosted HIV protease inhibitor drugs

This update is in follow-up to the FDA Drug Safety Communication¹: Important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs on 2/4/2012.

Safety Announcement

[4-26-2012] The U.S. Food and Drug Administration (FDA) is notifying the public that co-administration of Victrelis (boceprevir), a hepatitis C virus (HCV) protease inhibitor, along with certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors, is not recommended at this time because of the possibility of reducing the effectiveness of the medicines, permitting the amount of HCV or HIV virus in the blood (viral load) to increase. Ritonavir-boosted HIV protease inhibitors include ritonavir-boosted Reyataz (atazanavir), ritonavir-boosted Prezista (darunavir), and Kaletra (lopinavir/ritonavir).

Patients should not stop taking any of their hepatitis C or HIV medicines without talking to their healthcare professional. Patients should contact their healthcare professional with any questions or concerns.

Healthcare professionals who started patients infected with both chronic HCV and HIV on Victrelis while the patient was taking antiretroviral therapy containing one of these ritonavir-boosted protease inhibitors should closely monitor patients for treatment response (no HCV virus detected in the blood) and for potential HCV or HIV virologic rebound (HCV or HIV virus is detected in the blood again after becoming undetectable).

Ritonavir is an HIV protease inhibitor that is taken as a small dose along with other HIV protease inhibitors in order to increase their levels in the blood and make them more effective. This is known as ritonavir boosting.

In February 2012², FDA issued a Drug Safety Communication (DSC) regarding a drug-drug interaction study, which showed that taking Victrelis while taking any one of the three ritonavir-boosted HIV protease inhibitors could reduce the desired blood levels of both medicines. Because lower blood levels could lead to less effective treatment of HCV and HIV infections, FDA recommended that healthcare professionals closely monitor the treatment response of patients who might be taking these drug combinations.

There is limited information on the effectiveness of Victrelis and ritonavir-boosted HIV protease inhibitors when they are used together in patients co-infected with HIV and HCV. A small clinical trial measured treatment outcomes of HIV-HCV co-infected patients whose HCV infection was treated with either peginterferon/ribavirin or boceprivir plus peginterferon/ribavirin and whose HIV infection was treated with ritonavir-boosted atazanavir, ritonavir-boosted darunavir, lopinavir/ritonavir, or raltegravir (Isentress). Persons who received boceprevir plus peginterferon/ribavirin were more likely to have undetectable HCV viral loads 12 weeks after completing HCV treatment than individuals who received peginterferon/ribavirin alone. Overall, seven patients had HIV virologic rebound, 3/64 randomized to receive boceprevir with peginterferon/ribavirin and 4/34 randomized to peginterferon/ribavirin alone. Preliminary results of this clinical trial were presented at the 19th Conference on Retroviruses and Opportunistic Infections on March 6, 2012. The clinical trial abstract is available here³.

In light of both the findings of the drug-drug interaction study and the clinical trial, FDA has revised the Victrelis drug label to state that co-administration of Victrelis with ritonavir-boosted Reyataz (atazanavir), ritonavir-boosted Prezista (darunavir), or Kaletra (lopinavir/ritonavir) to patients infected with both chronic HCV and HIV is not recommended at this time.

FDA is aware that a larger clinical trial⁴ is planned that will evaluate HCV treatment with boceprevir and peginterferon/ribavirin in patients infected with both HCV and HIV who are also receiving HIV antiretroviral therapy containing ritonavir-boosted HIV protease inhibitors. FDA will communicate any important new information about co-administration of these drugs in co-infected patients when it becomes available.

-

Related Information

• FDA Drug Safety Communication: Important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs⁵

Victrelis (boceprevir) Information⁶

 

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Southern Research Signs Agreement with Apath, LLC to Conduct Preclinical Studies with Virus-Based HCV Screenings

PRESS RELEASE

April 25, 2012, 1:15 p.m. EDT

BIRMINGHAM, Ala., April 25, 2012 /PRNewswire via COMTEX/ -- Southern Research today announced that it has signed an agreement with Apath, LLC which will allow Southern Research to conduct laboratory testing, research, and/or screening of potential therapeutic agents for hepatitis C (HCV) on an exclusive, fee-for-service basis using Apath's HCV virus-based technology.

Apath--a privately held technology company focusing on HCV and other human viral pathogens--was founded by Charles M. Rice, Ph.D., Professor at The Rockefeller University and formerly of the Washington University School of Medicine.

"Preclinical screening using a virus-based system will advance potential treatments for the disease because new therapies for HCV will be screened against the actual virus rather than a subset of the replication machinery," said Andrew D. Penman, Ph.D. vice president of Drug Development at Southern Research. "We are very pleased to work with Dr. Rice, a world renowned HCV expert and offer this new service to our clients."

Most preclinical drug screening for new HCV therapies use cell lines that harbor replicons--intracellular sub-genomic, self-replicating RNA molecules that contain the nucleotide sequences required for RNA replication, transcription, and translation, but are not themselves infectious.

Using a virus-based system, researchers can now develop antiviral treatments targeting viral entry into the cell, all of the replication machinery of the replicon, as well as downstream events such as viral assembly and release from the cell. As such, the entire viral life cycle is available for drug discovery and development.

"Successful treatment for chronic hepatitis C, given HCV diversity and the spectrum of disease, is likely to require combination therapy and new drugs well beyond those already approved," said Dr. Rice.

"As part of our commitment to remaining the global leader in the sublicensing of HCV-related technologies, I am particularly pleased with the expansion of our contract services agreement with Southern Research Institute, and I am extremely encouraged by the potential of this business venture assisting our clients in the fight against hepatitis C," said Robert M. Roth, Apath vice president, Strategic Operations.

Southern Research conducts both contract research and basic research for clients, providing preclinical drug discovery, development, and clinical trial support services in cancer, infectious diseases, and CNS/neurological disease to pharmaceutical and biotechnology companies. Scientists conduct translational science to invent small molecules and advance them from the design stage to the clinic. Services available include medicinal chemistry, molecular biology, biochemistry, high-throughput screening and a full set of in-house GLP development services including toxicology, ADME/PK, animal models, formulations, and bioanalytical services.

ABOUT SOUTHERN RESEARCHSouthern Research Institute is a not-for-profit 501(c)(3) scientific research organization founded in 1941 that conducts preclinical drug discovery and development, advanced engineering research in materials, systems development, and environment and energy research. More than 550 scientific and engineering team members support clients and partners in the pharmaceutical, biotechnology, defense, aerospace, environmental and energy industries. Southern Research is headquartered in Birmingham, Ala., with facilities in Wilsonville, Ala., Frederick, Md., and Durham, NC and offices in Huntsville, Ala., New Orleans, La., and Washington, DC.

CONTACT: Rhonda Jung 205-337-9634 Jung@SouthernResearch.org

Source

SOURCE Southern Research Institute