Response to Comments on An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection

An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases

These evidence-based guidelines are developed and updated regularly by a committee of hepatology experts and include recommendations of preferred approaches to the diagnostic, therapeutic, and preventive aspects of care.

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Response to Comments on An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection

1) I think the guidelines are fine. I do have a question as to follow up of a Genotype 1 patient who does not want treatment and also the Genotype 1 patient who fails triple therapy?

Response:
Monitoring of patients with all genotypes who do not warrant or want treatment was not addressed in the guidelines. Frequency of monitoring should be based on underlying disease severity. Patients with mild disease could be seen every six months while those with more advanced disease should be seen every three to four months; this recommendation is based on expert opinion. Patients with cirrhosis need to be considered for periodic surveillance for esophageal varices and hepatocellular carcinoma as per AASLD guidelines on Management of Esophageal Varices and Hepatocellular Carcinoma.
2) There is no consideration for IL28B testing to determine if some patients are good candidates for double therapy with Pegylated Interferon with Ribavirin vs. triple therapy. Since, compliance is a major issue with the triple therapy, providing an option with double therapy to patients who would respond well based on IL28B should be addressed.

Response:
The advantages of using PI-based treatment even in persons with IL28B genotype CC are that more persons will qualify for abbreviated therapy with telaprevir and possibly boceprevir, and there are higher SVR rates than double therapy. The advantages of treating IL28B genotype CC patients with peginterferon and ribavirin alone are fewer side effects, fewer drug-drug interactions, and lower cost. However, until cost effectiveness studies are published, we recommend the PI-based approach in most patients.

3) I am surprised there is so little commentary on which patients warrant treatment. This is a significant omission. Future guidelines and commentary should include a balanced discussion framing the pros and cons of treatment according to typical patient scenarios. These therapies are still prone to many side effects, and many patients have little urgency to treat, yet are feeling pressured to participate.

Response:
This question was beyond the scope of our mandate and will be reconsidered in the next full update to the guidelines. The issue is a highly controversial one with many different opinions. Many factors go into the decision regarding whom to treat including disease severity, likelihood of response, benefits and risks of treatment, as well as the likelihood of new therapeutic options. As efficacy and safety of therapy improves many of these factors may become less important and it is likely that most patients will become candidates for therapy.

4) The #16 recommendation of the guideline is somewhat contradictory to the #9 recommendation: In #9, the futility rule is described as the following: "telaprevir, peginterferon alfa and ribavirin should be stopped if the HCVRNA level is >1,000 IU/ml at treatment weeks 4 or 12". But in #16 it says that "the protease inhibitor should be discontinued if virological breakthrough (>1 log increase in serum HCVRNA above nadir) is observed". If telaprevir was used, there are occasions HCVRNA measured 10 times higher from nadir (e.g. Around 10 IU/ml to the hundreds but well within 1000 IU/ml futility limit) during telaprevir dosing period. If the clinician follows #9, telaprevir should be continued but if #16 was followed, telaprevir needs to be stopped. Therefore, this inconsistency needs to be addressed.

Response:
The two statements are not contradictory. To clarify, the stopping rule in #9 applies to patients who reach a virological plateau after which continued therapy would significantly increase the risk for antiviral resistance. Recommendation #16 deals with compliant patients who experience virological breakthrough signifying the emergence of antiviral resistance. Although the author is correct, among the patients with virological breakthrough, their HCV RNA may increase from undetected to 100 IU/ml and still be under the 1,000 IU/ml rule; the important point is the change from a negative to a positive test.

Source

Idenix Seeks Partner for Hepatitis C Combination, CEO Says

January 13, 2012 9:05 PM

(Updates with closing share price in sixth paragraph.)

Jan. 13 (Bloomberg) -- Idenix Pharmaceuticals Inc., the developer of an experimental hepatitis C drug, is in talks to find a partner to create a combination treatment to fight the virus, Chief Executive Officer Ron Renaud said.

“If we think about how we can be very competitive, it is going to be about combining our compound with others,” Renaud said in an interview at the J.P. Morgan Healthcare Conference in San Francisco. That will be “our whole strategy.”

The Cambridge, Massachusetts-based biotechnology company finished the year with $118 million in cash, “enough to take us through to the end of this year,” Renaud said. There is a mid- year goal to find a partner for their drug, as part of a process of “evaluating paths forward,” he said.

The development of drug cocktails for HIV, the virus that causes AIDS, “is a very good road map for what could happen in hepatitis C,” Renaud said. HIV treatment involves a “combination of compounds with different mechanisms of action and compensating resistance profiles that beat the disease.”

Renaud declined to comment on whether the company may be acquired as the result of other recent purchases in the hepatitis C field.

Idenix gained 13 percent to $14.42 at the close in New York. The shares have more than doubled since Jan. 7 when Bristol-Myers Squibb Co. said it would pay about $2.5 billion in cash for Inhibitex, a rival in a possible $20 billion hepatitis C market. Pharmasset, the maker of another experimental treatment for the virus, agreed on Nov. 21 to be acquired by Gilead Sciences Inc. for $10.8 billion.

Safer Treatments

As many as 170 million people worldwide carry the hepatitis C virus, and current drugs, given through injection, can have side effects that make therapy difficult to endure. The new medicines are designed to be taken as pills, with a higher cure rate and fewer side effects.

On Jan. 9, Idenix reported that its lead drug candidate for hepatitis C, called IDX184, showed no serious side effects in patients after 28 days of treatment. Renaud said the company had submitted the data to the U.S. Food and Drug Administration, and expects to hear whether restrictions on its trials are lifted within a month.

“We are certainly going to combine IDX184 with protease inhibitors, and maybe a NS5A inhibitor,” Renaud said yesterday, describing drugs that attack different checkpoints for the disease as it moved through the human body.

While people are “very excited about the prospects” of an Idenix takeover, at current trading levels, the “valuation is very rich for M&A,” said Brian Skorney, an analyst at Brean Murray Carret & Co in New York.

Skorney said IDX184 needs another potent drug to “cover for its weaknesses” and pointed toward Merck & Co., the second- largest U.S. drugmaker, as an ideal suitor with its experimental protease inhibitor, MK-5172. He said Johnson & Johnson, the world's biggest health-care products company, also may have an interest because of its hepatitis C research program.

--Editors: Andrew Pollack, Angela Zimm

Source

Adjuvant interferon doesn't prevent HCC recurrence

Last Updated: 2012-01-06 15:13:29 -0400 (Reuters Health)

By David Douglas and Nancy Lapid

NEW YORK (Reuters Health) - Postoperative therapy with interferon alfa-2b doesn't keep hepatitis-related hepatocellular carcinoma (HCC) from recurring, Taiwanese researchers have found.

As Dr. Pei-Jer Chen, who headed the study, told Reuters Health by email, "Interferon alfa 2b adjuvant therapy failed to reduce HCC recurrence or (improve) overall survival in patients receiving surgical resection. Now other combination adjuvant therapies are urgently needed."

In a report this month in Annals of Surgery, Dr. Chen of National Taiwan University College of Medicine, Taipei and colleagues note that although most individual trials of adjuvant interferon in this setting had failed, meta-analyses had suggested that interferon alfa-2b could be of benefit after curative ablation.

To investigate further, the researchers enrolled 268 patients in a randomized trial of adjuvant interferon alfa-2b, or no interferon, after curative surgery. Eighty percent of the patients had hepatitis B virus (HBV) surface antigen; the others had hepatitis C.

During a median follow-up of slightly more than five years, 58% had tumor recurrence and 31% died. Intention-to-treat analysis gave a five-year recurrence-free survival of 44.2% and overall survival of 73.9%.

Overall, the median recurrence-free survival was 42.2 months in the interferon group and 48.6 months in controls. Broken down by etiology, disease-free survival in the interferon and control groups, respectively, was 42.2 and 31.1 months with HCV and 42.4 and 49.1 months with HBV. None of these differences was statistically significant.

As could be expected, side effects were more common with interferon. Treated patients had a significantly higher incidence of leukopenia and thrombocytopenia.

Viral replication was only temporarily suppressed during the treatment, and the researchers suggest that "studies to investigate a more permanent inhibition of HCV replication by pegylated interferon alfa/ribavirin combinations deserve further exploration." For HBV, they add, oral nucleoside analogs may be of use.

Dr. Chen and colleagues began enrolling patients in this trial more than seven years ago. Dr. Yuman Fong from Memorial Sloan-Kettering Cancer Center in New York City, who was not involved in Dr. Chen's study, confirmed for Reuters Health that in the years since that trial was designed, nothing more promising has appeared on the horizon.

It's "very sad," he said in an email, "since 750,000 patients get HCC each year."

If he were doing the study now, Dr. Fong added, he "would take only patients with detectable virus in blood and randomize to current generation antivirals."

SOURCE: http://bit.ly/uMPbn6

Ann Surg 2011

Source

Lab in Hep C progress

By Jonathan Mayo | Last updated: 11:47, 12/01/2012

The first clinical trial in humans of a new hepatitis C vaccine has shown promising results, Oxford University researchers have announced.

The results of the trial suggest it may be possible to develop a vaccine which will offer protection against hepatitis C for over a year, and could allow those with infections to be treated. The team of researchers, led by Professor Paul Klenerman and Dr Ellie Barnes of the Nuffield Department of Clinical Medicine, carried out the trial on 41 healthy adults for a year. Professor Klenerman said: “The immune responses we’ve seen are exciting and we are beginning the next stage of trials.” However, he also emphasised that: “While we are hopeful, it could be a long road to any vaccine that protects people against hepatitis C.”

There are currently thought to be around 250,000 people in England and Wales who are infected with hepatitis C. The disease leads to chronic liver damage, often requiring a transplant.

Source

Also See: Experimental hepatitis C vaccine shows early promise

HIV Transmission: 1 in 900 Sex Acts Transmits Virus

An image of the human immunodeficiency virus (HIV), taken with a scanning electron microscope. The multiple round bumps on the cell surface represent sites of assembly and budding of HIV particles. HIV is responsible for Acquired Immunodeficiency Syndrome (AIDS).

CREDIT: Cynthia Goldsmith, Centers for Disease Control and Prevention

Jan 12, 2012 | 9:37 AM ET | Rachael Rettner, MyHealthNewsDaily Staff Writer

A heterosexual person infected with HIV will transmit the virus to their partner once in every 900 times the couple has unprotected sex, according to a new study conducted in Africa.

However, the exact number of sexual acts that are needed to transmit the virus can vary tremendously depending on the amount of the virus in the infected person's blood, said study researcher James Hughes, of the University of Washington in Seattle.

In fact, the amount of virus in the blood is the single most important factor in determining whether HIV is passed between sexual partners, the study found. For every tenfold increase in the concentration, there is about a threefold increase in the risk of transmission during a single sexual act.

People with very high blood concentrations of the virus (such as those who very recently acquired the infection) may need to have sex only 10 times to transmit the virus, Hughes said. "The average can be a little deceptive," Hughes said.

The new findings reinforce the idea that the best methods for reducing HIV transmission are those that decrease the concentration of the virus in the blood, as can be done with antiretroviral drugs, Hughes said. A study published last year found the drugs could reduce the transmission of HIV between partners by 96 percent.

The new study also confirmed condoms are highly effective in preventing HIV infection, reducing the risk of transmission by 78 percent. Male circumcision reduced the risk of HIV transmission by 47 percent.

HIV transmission

Earlier studies attempted to estimate the rate of HIV transmission, but were typically quite small, and did not measure the concentration of the virus in the blood throughout the entire study period.

The new study included 3,297 couples from sub-Saharan Africa that were "HIV-discordant," meaning one partner had HIV while the other did not. The HIV-infected partners in the study were tested periodically over the two-year study for the amount of HIV in their blood. Infected partners were also interviewed every month and asked how many times they had sex, and whether they used protection.

The uninfected partners were tested periodically to see whether they had acquired HIV. The researchers used genetic testing of the virus to confirm that any new HIV infections had been acquired from the study partner designated at the study's start.

Eighty-sixHIV transmissions occurred during the study period.

Men were about twice as likely to transmit HIV to women as women were to men. This increased risk of transmission could be attributed to higher virus concentrations in the blood of men compared with women, according to the study. In addition, women were more likely to have genital herpes, which increases susceptibility to HIV.

Condoms were reported to be used in 93 percent of sexual acts, but the researchers suspect their use was overreported. Therefore, condoms actually may be even more effective at preventing HIV transmission than the 78 percent reduction that the researchers estimated, Hughes said.

The AIDS epidemic

The study relied on self-reports, which might be wrong. However, errors in reports of the number of sexual acts would be unlikely to affect most of the study results, Hughes said.

The average risk of HIV infection per sexual act estimated in the study is consistent with what has been found by previous research, but there are many situations in which that number may not apply," said Dr. Myron Cohen, a professor of medicine, microbiology, immunology and public health at the University of North Carolina at Chapel Hill, who was not involved in the work.

That's because the participants included in the study are couples that have remained together and discordant over a long period of time. This indicates the couples might have some biological protection against transmission, Cohen said.

"The true estimation might be higher if you were studying different kinds of people," Cohen said.

While most of the findings are likely generalizable to other countries, the number of sexual acts needed to transmit the virus is likely specific to the African population studied, Hughes said. Previous studies in the United States have found a lower transmission rate.

In addition, the findings only apply to heterosexual couples, and not men who have sex with men, a group that is likely to have a much higher transmission rate, Hughes said.

Pass it on: The best way to reduce the risk of HIV transmission is to lower the amount of the virus in the blood.

Source

Vital Signs: HIV Prevention Through Care and Treatment

From Morbidity & Mortality Weekly Report

United States

Stacy M. Cohen, MPH; Michelle M. Van Handel, MPH; Bernard M. Branson, MD; Janet M. Blair, PhD; H. Irene Hall, PhD; Xiaohong Hu, MS; Linda J. Koenig, PhD; Jacek Skarbinski, MD; Angie Tracey, Jonathan Mermin, MD; Linda A. Valleroy, PhD

Posted: 01/12/2012

Abstract and Introduction

Abstract

Background: An estimated 1.2 million persons in the United States were living with human immunodeficiency virus (HIV) infection in 2008. Improving survival of persons with HIV and reducing transmission involve a continuum of services that includes diagnosis (HIV testing), linkage to and retention in HIV medical care, and ongoing HIV prevention interventions, including appropriately timed antiretroviral therapy (ART).
Methods: CDC used three surveillance datasets to estimate recent HIV testing and HIV prevalence among U.S. adults by state, and the percentages of HIV-infected adults receiving HIV care for whom ART was prescribed, who achieved viral suppression, and who received prevention counseling from health-care providers. Published data were used to estimate the numbers of persons in the United States living with and diagnosed with HIV and, based on viral load and CD4 laboratory reports, linked to and retained in HIV care.
Results: In 2010, 9.6% of adults had been tested for HIV during the preceding 12 months (range by state: 4.9%–29.8%). Of the estimated 942,000 persons with HIV who were aware of their infection, approximately 77% were linked to care, and 51% remained in care. Among HIV-infected adults in care, 45% received prevention counseling, and 89% were prescribed ART, of whom 77% had viral suppression. Thus, an estimated 28% of all HIV-infected persons in the United States have a suppressed viral load.
Conclusions: Prevalence of HIV testing and linkage to care are high but warrant continued effort. Increasing the percentages of HIV-infected persons who remain in HIV care, achieve viral suppression, and receive prevention counseling requires additional effort.
Implications for Public Health Practice: Public health officials and HIV care providers should improve engagement at each step in the continuum of HIV care and monitor progress in every community using laboratory reports of viral load and CD4 test results.

Introduction

Human immunodeficiency virus (HIV) causes a chronic infection that leads to a progressive disease. Without treatment, most persons with HIV develop acquired immunodeficiency syndrome (AIDS) within 10 years of infection, which results in substantial morbidity and premature death.^[1] Approximately 50,000 persons in the United States were infected with HIV annually during 2006–2009.^[2] Approximately 16,000 persons with AIDS die each year.^[3] A consistently suppressed HIV viral load is associated with reduced morbidity and mortality and a lower probability of transmitting HIV to sex partners.^[4] Testing identifies infected persons and is the entry point to a continuum of HIV health-care and social services that improve health outcomes, including survival. This continuum includes diagnosis (HIV testing), linkage to and retention in continuous medical care for HIV, prevention counseling and other services that reduce transmission, and appropriately timed and consistent antiretroviral therapy (ART) for viral suppression. This report estimates the number of HIV-infected persons who received selected services along the continuum of HIV care in the United States and the overall percentage of persons with HIV who had a suppressed viral load.

Methods

Data reported through June 2010 to the National HIV Surveillance System were used to calculate rates* by state per 100,000 population among persons aged 18–64 years living with diagnosed HIV infection (prevalence) at the end of 2008. Behavioral Risk Factor Surveillance System^† data from 2010 were used to estimate percentages by state of persons aged 18–64 years who reported testing for HIV during the 12 months preceding the interview. Medical Monitoring Project (MMP)^§ data were used to estimate numbers and nationally representative percentages of adults aged ≥18 years receiving medical care who reported receiving prevention counseling in a clinical setting^¶ during the 12 months preceding the interview, and whose medical record documented that they 1) were prescribed ART during the 12 months preceding the interview and 2) had a suppressed viral load (defined as ≤200 copies/mL) at their most recent test.

Using these surveillance data and published information, CDC assessed the estimated number of persons with HIV infection^[7] and the numbers and percentages of persons who were 1) aware of their infection,^[7] 2) linked to care,^[8,9] 3) retained in care (8–11), 4) prescribed ART, and 5) virally suppressed. From these analyses, CDC developed a national estimate of the percentage of all HIV-infected persons with viral suppression.

* Diagnosed HIV prevalence rates were not adjusted for reporting delays to allow inclusion of all 50 states and the District of Columbia. By June 2010, only 40 states had implemented confidential name-based HIV infection reporting for long enough (since at least January 2006) to allow for stabilization of data collection and adjustment for reporting delays.
^† The Behavioral Risk Factor Surveillance System is a state-based, random-digit-dialed telephone survey of the civilian, noninstitutionalized adult population that collects information on preventive health practices and risk behaviors in the United States.^[5]
§ MMP collects behavioral and clinical information from a nationally representative sample of adults receiving medical care for HIV infection in outpatient facilities in the United States and Puerto Rico.^[6] A total of 23 project areas were funded to conduct data collection activities for the 2009–2010 MMP data collection cycle: California; Chicago, Illinois; Delaware; Florida; Georgia; Houston, Texas; Illinois; Indiana; Los Angeles County, California; Michigan; Mississippi; New Jersey; the state of New York; New York City, New York; North Carolina; Oregon; Pennsylvania; Philadelphia, Pennsylvania; Puerto Rico; San Francisco, California; Texas; Virginia; and Washington. Patients who received medical care during January–April 2009 at an MMP participating facility were interviewed once during June 2009–April 2010 regarding all medical visits during the 12 months preceding the interview. In addition, patients' medical records were abstracted for documentation of medical care (including prescription of ART and HIV viral load) for the 12 months preceding the interview. All percentages were weighted for the probability of selection and adjusted for nonresponse bias.
^¶ Based on self-reported information from the patient interview about discussions with a physician, nurse, or other health-care worker. Topics might have included condom negotiation, how to practice safer sexual behavior or injection use, or how to talk with partners about safe sex. Discussion occurring during sessions that were part of HIV testing and counseling encounters were not included.

Results

In 2008, an estimated 1.2 million persons were living with HIV in the United States, of whom 80% had been diagnosed.^[7] The prevalence rate for persons aged 18–64 years with an HIV diagnosis ranged by state from 40.1 to 3,365.2 per 100,000 population (Figure 1). In 2010, an estimated 9.6% of persons aged 18–64 years reported recent HIV testing (range by state: 4.9%–29.8%) (Figure 2). In general, recent HIV testing percentages were higher in states with higher HIV prevalence rates.

Figure 1. Rates of persons aged 18–64 years living with a diagnosis of HIV infection* — National HIV Surveillance System, United States, year-end 2008
Abbreviation: HIV = human immunodeficiency virus.
* Rates are per 100,000 population and are not adjusted for reporting delays. Rates are categorized into quintiles. Overall rate: 417.5 per 100,000 population.

Figure 2. Percentages of persons aged 18–64 years tested for HIV infection during the preceding 12 months — Behavioral Risk Factor Surveillance System, United States, 2010
Abbreviation: HIV = human immunodeficiency virus.
* Percentages are categorized into quintiles. Overall percentage: 9.6%.

According to published studies, approximately 77% of persons diagnosed with HIV were linked to care within 3–4 months of diagnosis,^[8,9] and 51% were retained in ongoing care (8–11). Among adults aged ≥18 years in MMP representing persons receiving HIV medical care, 89% had been prescribed ART. Of these, 77% had a suppressed viral load at their most recent test (Table). CDC synthesized these findings to determine the number of persons in selected categories of the continuum of HIV care (Figure 3), and estimated that 328,475 (35%) of 941,950 persons diagnosed with HIV (or 28% of all 1,178,350 persons with HIV) in the United States are virally suppressed.

Figure 3. Number and percentage of HIV-infected persons engaged in selected stages of the continuum of HIV care — United States
Abbreviations: HIV = human immunodeficiency virus; ART = antiretroviral therapy.
* HIV-infected, N = 1,178,350; HIV-diagnosed, n=941,950. Source: CDC. HIV surveillance—United States, 1981–2008. MMWR 2011;60:689–93.
^† Calculated as estimated number diagnosed (941,950) × estimated percentage linked to care (77%); n = 725,302. Sources: Marks G, Gardner LI, Craw J, Crepaz N. Entry and retention in medical care among HIV-diagnosed persons: a meta-analysis. AIDS 2010;24:2665–78; Torian LV, Wiewel EW. Continuity of HIV-related medical care, New York City, 2005–2009: do patients who initiate care stay in care? AIDS Patient Care STDS 2011;25:79–88.
^§ Calculated as estimated number diagnosed (941,950) × estimated percentage retained in care (51%); n = 480,395. Sources: Marks G, Gardner LI, Craw J, Crepaz N. Entry and retention in medical care among HIV-diagnosed persons: a meta-analysis. AIDS 2010;24:2665–78; Torian LV, Wiewel EW. Continuity of HIV-related medical care, New York City, 2005–2009: do patients who initiate care stay in care? AIDS Patient Care STDS 2011;25:79–88; Hall IH, Mahle KC, Tang T, Li J, Johnson AS, Shouse L. Retention in care of HIV-infected adults and adolescents in 13 U.S. areas. Presented at the National HIV Prevention Conference, Atlanta, GA, August 14–17, 2011; Tripathi A, Youmans E, Gibson JJ, Duffus WA. The impact of retention in early HIV medical care on viro-immunological parameters and survival: a statewide study. AIDS Res Hum Retroviruses 2011;27:751–8.
^¶ Calculated as estimated number retained in HIV care (480,395) × percentage prescribed ART in MMP (88.8%); n = 426,590. Source: Data from the Medical Monitoring Project.
** Calculated as estimated number on ART (426,590) × percentage with suppressed viral load in MMP (77.0%); n = 328,475 (28% of the estimated 1,178,350 persons in the United States who are infected with HIV). Source: Data from the Medical Monitoring Project.

The percentages of patients in MMP who were prescribed ART, had documented viral suppression, and received prevention counseling from a health-care provider during the preceding 12 months varied by age group, race/ethnicity, and reported sexual behavior (Table). Prescription of ART ranged from 76% for patients aged 18–24 years to 92% for those aged ≥55 years; of those prescribed ART, viral suppression was lowest among patients aged 25–34 years (69%) and highest in those aged ≥55 years (85%). Among the 92% of whites, 89% of Hispanics or Latinos, and 86% of blacks or African Americans who were prescribed ART, 84% of whites and 79% of Hispanics or Latinos had documented viral suppression, compared with 70% of blacks or African Americans. ART prescriptions were documented for 91% of men who have sex with women only (MSW), 89% of men who have sex with men (MSM), and 86% of women who have sex with men (WSM). By sex, 79% of males (81% of MSM and 75% of MSW) had viral suppression, compared with 71% of females.

Among persons in MMP, 45% had received prevention counseling during the preceding year, ranging from 36% among persons aged ≥55 years to 73% among persons aged 18–24 years. By race/ethnicity, 54% of blacks or African Americans and 52% of Hispanics or Latinos received prevention counseling, compared with 29% of whites. Prevention counseling was received by 50% of MSW and WSM, but only 39% of MSM.

Conclusions and Comment

Among MMP participants (representing adults aged ≥18 years receiving medical care for HIV infection), 89% had been prescribed ART, of whom 77% had a suppressed viral load. However, only 28% of all persons living with HIV infection in the United States are estimated to be virally suppressed, in large part because only approximately 41% are both aware of their infection and receiving ongoing HIV care.

The observed higher percentages of persons who were recently tested in areas with higher HIV prevalence are encouraging. These findings are consistent with the recommendations of the 2010 National HIV/AIDS Strategy to intensify efforts in communities where HIV is concentrated most heavily, but continued effort is necessary to achieve the goal of increasing the proportion of persons aware of their infection from 80% to 90%.^[12] CDC's comprehensive HIV testing strategy includes 1) routine HIV screening in health-care settings with prevalence of undiagnosed infection ≥0.1%, 2) targeted testing of persons with risk factors associated with increased HIV prevalence, and 3) retesting at least annually for HIV-negative persons at increased risk for HIV.^[13]

Although the percentage of persons with HIV who are linked to care after diagnosis is 77%, more effort is needed to ensure that those patients remain in care and to eliminate disparities among subgroups who are prescribed ART and subsequently achieve viral suppression. In MMP, compared with whites, smaller percentages of blacks or African Americans and Hispanics or Latinos were prescribed ART and were virally suppressed. Differences in rates of ART prescription and viral suppression might reflect differences in insurance coverage, prescription drug costs, health-care providers' perceptions of patients' probability of adherence, or other factors associated with adherence.

Ongoing prevention interventions for persons with HIV infection are key components to reduce HIV transmission. Prevention counseling is recommended as an ongoing part of HIV care for all patients,^[14] but fewer than half of patients in MMP had received prevention counseling from their health-care provider during the preceding year. These low percentages, especially among MSM, who account for the most new HIV infections in the United States,^[2] indicate a need for health-care providers to deliver HIV prevention services more consistently.

The findings in this report are subject to at least two limitations. First, documentation of a recent suppressed viral load might not be indicative of consistent viral suppression. Second, the percentage of persons with viral suppression might be overestimated or underestimated and not representative of all persons with HIV in the United States because 1) not all states have implemented routine reporting of CD4 and viral load test results, so estimates of percentages of persons retained in care are based on a limited number of states; 2) MMP data might include persons more likely to be retained in care or adhere to ART; and 3) the estimate assumed no viral suppression among persons not in care, although a small percentage of persons demonstrate viral suppression without taking ART.

CDC's estimate that 28% of all HIV-infected persons are virally suppressed is higher than the 19% reported in a recent review.^[15] CDC used more recent data and different methods that did not depend on estimates of the proportion of persons in care who need ART. The previous estimate calculated that 80% of persons in care need ART, of whom 75% receive it.^[15]

The 2010 National HIV/AIDS Strategy goals of reducing HIV incidence, increasing access to care and improving health outcomes for persons living with HIV, and reducing HIV-related disparities and health inequities are interdependent. Reducing national HIV incidence and improving individual health outcomes require increased access to care and elimination of disparities in the quality of care received. To meet these goals and break the cycle of HIV transmission in the United States, achieving high levels of engagement at every stage in the continuum of care is essential. Currently, a substantial proportion of HIV-infected persons have been tested and initially linked to care, and of those retained in care, 89% are prescribed ART, and 77% achieve viral suppression. However, only an estimated 28% of all HIV-infected persons in the United States are virally suppressed, largely because even among those with diagnosed infection, only 51% are receiving regular HIV care (8–11). Without substantial improvement in these percentages, 1.2 million new HIV infections would be expected to occur in the United States over the next 20 years.^[16] Based on estimated lifetime HIV treatment costs of $367,000 per person (2009 dollars)^[17] caring for persons who become infected could cost as much as $450 billion in health-care expenditures.^[16]

CDC supports state and local health department programs to expand and monitor HIV testing and linkage to medical care, especially in high prevalence areas. Because ensuring that persons with HIV infection receive continuous medical care is important, CDC is working with health departments throughout the nation to expand their efforts to collect laboratory reports on all CD4 and viral load test results for persons diagnosed with HIV. Local programs can use these data (in accordance with privacy and confidentiality policies, laws, and regulations) to identify persons not in care and to facilitate efforts to ensure they receive appropriate care. CDC will continue using MMP to monitor receipt of ART and prevention services among persons in care and identify opportunities for improvement. CDC will share this information with grantees, partners, health-care providers, and other federal agencies (e.g., the Health Resources and Services Administration) to improve the delivery of care, treatment, and prevention services for all persons with HIV infection.

The results in this report indicate that progress has been made; however, continued and intensified efforts are needed. Only with success at each step in the continuum of HIV care (i.e., identifying those with HIV, linking them to and retaining them in care, and ensuring they receive optimal treatment and prevention services) can the ultimate goals of improving health, extending lives, and preventing further HIV transmission be achieved.

References

1. Hall HI, McDavid K, Ling Q, Sloggett A. Determinants of progression to AIDS or death after HIV diagnosis, United States, 1996 to 2001. Ann Epidemiol 2006;16:824–33.
2. Prejean J, Song R, Hernandez A, et al. Estimated HIV incidence in the United States, 2006–2009. PLoS One 2011;6:e17502.
3. CDC. Diagnoses of HIV infection and AIDS in the United States and dependent areas, 2009. HIV surveillance report, Volume 21. Atlanta, GA: US Department of Health and Human Services, CDC; 2011. Available at http://www.cdc.gov/hiv/surveillance/resources/reports/2009report/index.htm. Accessed October 25, 2011.
4. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365:493–505.
5. CDC. Behavioral Risk Factor Surveillance System Survey. Atlanta, GA: US Department of Health and Human Services, CDC; 2010. Available at http://www.cdc.gov/brfss. Accessed October 25, 2011.
6. CDC. Clinical and behavioral characteristics of adults receiving medical care for HIV infection: Medical Monitoring Project, United States, 2007. MMWR 2011;60(No. SS-11).
7. CDC. HIV surveillance—United States, 1981–2008. MMWR 2011;60:689–93.
8. Marks G, Gardner LI, Craw J, Crepaz N. Entry and retention in medical care among HIV-diagnosed persons: a meta-analysis. AIDS 2010;24:2665–78.
9. Torian LV, Wiewel EW. Continuity of HIV-related medical care, New York City, 2005–2009: do patients who initiate care stay in care? AIDS Patient Care STDS 2011;25:79–88.
10. Hall IH, Mahle KC, Tang T, Li J, Johnson AS, Shouse L. Retention in care of HIV-infected adults and adolescents in 13 U.S. areas. Presented at the National HIV Prevention Conference, Atlanta, GA, August 14–17, 2011.
11. Tripathi A, Youmans E, Gibson JJ, Duffus WA. The impact of retention in early HIV medical care on viro-immunological parameters and survival: a statewide study. AIDS Res Hum Retroviruses 2011;27:751–8.
12. White House Office of National AIDS Policy. National HIV/AIDS Strategy for the United States. Washington, DC: White House Office of National AIDS Policy; 2010. Available at http://www.aids.gov/federal-resources/policies/national-hiv-aids-strategy/nhas.pdf. Accessed October 25, 2011.
13. CDC. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 2006;55(No. RR-14).
14. CDC. Incorporating HIV prevention into the medical care of persons living with HIV: recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR 2003;52(No. RR-12).
15. Gardner EM, McLees MP, Steiner JF, Del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis 2011;52: 793–800.
16. Long EF, Brandeau ML, Owens DK. The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States. Ann Intern Med 2010;153:778–89.
17. Schackman BR, Gebo KA, Walensky RP, et al. The lifetime cost of current human immunodeficiency virus care in the United States. Med Care 2006;44:990–7.

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Fatigue in Cirrhosis Linked to Psychosocial Factors

By: DENISE NAPOLI, Clinical Psychiatry News Digital Network

Cirrhosis patients have significantly more fatigue than do matched controls from the general population, and this fatigue often persists 1 year after liver transplantation, reported Dr. Evangelos Kalaitzakis and colleagues in the February issue of Clinical Gastroenterology and Hepatology.

Moreover, that fatigue is highly correlated with depression and anxiety and it impairs quality of life, the authors wrote.

Dr. Kalaitzakis of the University of Gothenburg (Sweden) studied 108 cirrhosis patients seen at a single institution between May 2004 and April 2007. The patients’ mean age was 52 years, and 36 of the 108 were women.

At study entry, all patients completed the Fatigue Impact Scale (FIS), which assesses fatigue in the physical, psychosocial, and cognitive domains and gives a total fatigue score. Patients were compared with a random sample of the general Swedish population who were mailed identical surveys and matched to cirrhosis patients.

Patients scoring greater than two standard deviations above the general population cohort on the FIS were classified as being fatigued (Clin. Gastro. Hepatol. 2012 [doi:10.1016/j.cgh.2011.07.029]).

At baseline, cirrhosis patients scored significantly higher than controls on the total FIS score, as well as on the physical, psychosocial, and cognitive domains (P less than .001 for all).

Study participants also completed the Hospital Anxiety and Depression Scale (HAD). Significant depression and anxiety on the HAD were both highly correlated with total fatigue as measured by the FIS (P less than .001).

Indeed, compared with controls, cirrhosis patients were more likely to have borderline or significant anxiety (12% vs. 21% and 8% vs. 16%, respectively, P = .034) and borderline or significant depression (9% vs. 23% and 6% vs. 14%, respectively, P = .001), Dr. Kalaitzakis and associates reported.

Clinical factors played a role as well, according to the analysis. In univariate analysis, higher Child-Pugh class was significantly correlated with overall fatigue, as were current ascites or history of ascites (P less than .001 for all).

Current overt hepatic encephalopathy also was significantly correlated with overall fatigue, although somewhat less so than the other factors (P less than .05).

Factors not significantly related to total fatigue included liver disease etiology, existence of stable or bleeding varices, and malnutrition, the investigators said.

In fact, in multivariate analysis, FIS scores were only related to depression, anxiety, Child-Pugh score, and low serum cortisol levels, they wrote.

Overall, 66 out of the 108 patients completed a liver transplant, and follow-up data were available at 1 year on 60 of these.

"FIS domain and total scores had improved 1 year post-transplant, but transplant recipients still had higher physical fatigue compared to controls," Dr. Kalaitzakis and associates noted.

Of the 37 patients whose FIS scores before transplant had classified them as physically fatigued, 17 (46%) continued to be fatigued after transplant, wrote the authors.

Compared with the patients whose fatigue levels dropped post transplant, these 17 patients once again were more likely to have significant or borderline depression at baseline, according to the HAD (15% vs. 35% and 15% vs. 41%, respectively; P = .019).

"Psychological distress was found to be a major determinant of fatigue in cirrhosis," the authors concluded.

Although some previous studies have found that antidepressants do not improve fatigue, at least in cancer patients, "our findings ... indicate that patients with cirrhosis and significant anxiety or depression confirmed by a psychiatrist may benefit from specific treatment for these disorders, which could lead to improvement in fatigue," they wrote. "However, this would need to be formally tested in interventional trials."

Dr. Kalaitzakis and associates stated that they had no conflicts of interest to disclose and no grant support for this study.

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Role of hepatitis C virus genotype 3 in liver fibrosis progression--a systematic review and meta-analysis

J Viral Hepat. 2011 Nov;18(11):745-59. doi: 10.1111/j.1365-2893.2011.01481.x. Epub 2011 Jul 1.

Probst A, Dang T, Bochud M, Egger M, Negro F, Bochud PY.

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Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.

Abstract

The progression of liver fibrosis in chronic hepatitis C has long been considered to be independent from viral genotypes. However, recent studies suggest an association between Hepatitis C virus (HCV) genotype 3 and accelerated liver disease progression. We completed a systematic review and meta-analysis of studies evaluating the association between HCV genotypes and fibrosis progression. PubMed, Embase and ISI Web of Knowledge databases were searched for cohort, cross-sectional and case-control studies on treatment-naïve HCV-infected adults in which liver fibrosis progression rate (FPR) was assessed by the ratio of fibrosis stage in one single biopsy to the duration of infection (single-biopsy studies) or from the change in fibrosis stage between two biopsies (paired biopsies studies). A random effect model was used to derive FPR among different HCV genotypes. Eight single-biopsy studies (3182 patients, mean/median duration of infection ranging from 9 to 21 years) and eight paired biopsies studies (mean interval between biopsies 2-12 years) met the selection criteria. The odds ratio for the association of genotype 3 with accelerated fibrosis progression was 1.52 (95% CI 1.12-2.07, P = 0.007) in single-biopsy studies and 1.37 (95% CI 0.87-2.17, P = 0.17) in paired biopsy studies. In conclusion, viral genotype 3 was associated with faster fibrosis progression in single-biopsy studies. This observation may have important consequences on the clinical management of genotype 3-infected patients. The association was not significant in paired biopsies studies, although the latter may be limited by important indication bias, short observation time and small sample size.

© 2011 Blackwell Publishing Ltd.

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The Response to the AIDS Epidemic in 2012: A Crystal Ball and Roadmap

Professor Alan Whiteside

January 2012

Introduction

This short paper looks forward at the big issues and the events facing those engaged in the HIV and AIDS epidemic in 2012. I have used my perspective to frame the paper: this is writing as an economist, with 25 years’ experience, leading a social science-based research group working in southern Africa which is engaged in global debates and leadership.

The paper is a mixture of a roadmap of upcoming events (chief is the Washington International AIDS Conference (IAC)); and a crystal ball: much is uncertain in the response. We know in most of the world the HIV epidemic is under control: there are specific groups at risk, mostly those who are marginalised. In eastern and southern Africa, AIDS remains the challenge to the wellbeing and existence of some nations. The need to respond to particular epidemics rather than a global, homogenous reaction is problematic. AIDS is exceptional but just not everywhere, and this nuance needs attention.

Funding

A major issue as we enter 2012 is funding. By the end of 2011 it had become clear that international donor funding was declining. This is due to a number of factors: the financial crisis in Western nations; changing priorities - new governments want to make their own mark (particularly the case when there is a change in political party); and a perception that AIDS has been at the top of the agenda long enough and may have been overfunded.

We need money for treatment: many millions of people are being kept alive with antiretroviral drug therapy, in some countries there are simply not domestic resources available if international funding is cut. But prevention must remain a priority: it is only by reducing the number of new infections that the epidemic will be beaten. The UNAIDS Strategic Investment Framework set out the levels of resources that will be required.ⁱ What is less clear is where this will come from. It is worth remembering the United States has been the most generous donor to HIV for many decades, but there are growing signals this may not continue – both obliquely from the government and more directly from think tanks.ⁱⁱ

The questions are:

• How much is needed? (UNAIDS provides pointers).
• Where will it come from? We need to look at domestic resources in some countries.
• How will decisions be taken about allocating increasingly scarce resources?ⁱⁱⁱ
• Can services be expanded or are we going to battle just to maintain existing levels?

Prevention

There will not be any technological breakthroughs in 2012. Circumcision campaigns will continue (64% protection for uninfected men), but microbicides seem less feasible than a year ago. Work on vaccines will continue but is unlikely to yield anything in the short term. The International AIDS Society (IAS) is stepping up its ‘Towards an HIV Cure: Global Scientific Strategy’ and this will be on the agenda at the Washington IAC. In the absence of scientific breakthroughs we will have to rely on the slower, more complex social, economic and political interventions. There is evidence these work, but are long term, attributing causality is complex, and they lack appeal for donors. Of great concern to outsiders is the existence of two HIV prevention working groups: one led by UNAIDS and the other championed by the Bill and Melinda Gates Foundation (BMGF). This seems to be unnecessary duplication and a distraction.

There is a growing need to understand the epidemic in terms of gender relations; underlying cultural norms; economic status especially issues of equality; and political leadership. All of these are potentially fuzzy concepts and difficult to deal with but this is where the smart money is needed, (and it will not be a huge amount).

Health Systems

In the past 18 months issues of Health Systems (HS) have become an international priority. In order to deliver services, be they prevention or therapy there is a need for reasonable, working health services. This is especially the case as international donors reduce funding and move away from vertical programmes. Much work needs to be done in this area. There is an event we can work towards: The Second Global Symposium on Health Systems Research in October 2012 in Beijing. The theme is Inclusion and Innovation Towards Universal Health Coverage see www.hsr-symposium.org This is not an HIV/AIDS meeting. The only bilateral organisation on the Executive Committee is the UK Department for International Development. The steering committee has better representation. The need in HS is to understand what is happening in a country and develop realistic, effective and efficient interventions.

Global Health Governance

There are concerns with regard to health governance generally. The World Health Organisation is still struggling to identify its comparative advantage in a crowded environment, and without significant resources. Of anxiety are the number of new initiatives developing and being housed in the organisation, each with their champions. The strategy for AIDS activists is to get the epidemic considered in each of these agendas.

UNAIDS is undergoing reorganisation and this always creates uncertainty – here a supportive and watching brief is critical. A great concern is the role of the Bill and Melinda Gates Foundation (BMGF). They are seen as so important and with such great resources that few are prepared to challenge their role and actions (speak truth to power). The 2011 appointment of Trevor Mundel, as President of the Global Health Program, and the imminent arrival of Christopher Elias from PATH as the new President of Global Development should lead to new thinking and strategies.

The apparent meltdown in the Global Fund (GF) for AIDS, TB and Malaria is a major worry. The cancellation of Round 11 and conflict between the Executive Director and Board at the end of 2011 remains unresolved. The proposed appointment of a general manager is a ‘band aid’ solution for a festering problem. There is a perception that some want to see the GF fail.

All the US agencies are facing cuts and an uncertain role – this is why the IAC is so critical. Central will be to give the US credit for what they have done, and understand the constraints and the political landscape. The champions in the USA need support and activism needs to be tempered.

One new initiative that feeds across many areas, the proposed ‘Multi-stakeholder Consultation on National AIDS Programmes Effectiveness, Efficiency and Sustainability’, at present is scheduled for 19 -20 March in Nairobi. This will look at the importance of achieving greater efficiency and effectiveness of HIV programmes. The starting point is all donors, most national governments in affected countries and other stakeholders have the efficiency and effectiveness (E2), and sustainability of HIV programmes at the top of their agendas. This will bring in work done by IAS in Uganda. The concern is people engage and see it as important, which has not been the case.

The Washington DC International AIDS Conference

This meeting, being held from 22- 27 July, with the theme of Turning the Tide Together, is going to be critical: one of the seminal conferences in the history of the epidemic.^iv In addition to the main meeting there will numerous pre-conference meetings and side events. This is most important for UNAIDS who will need to show strong leadership and produce a good global HIV report. It is the chance to show relevance and define the response for the next decade.

Treatment as Prevention

This will continue to generate a great deal of heat. The HPTN-052 study showed when a person is on treatment there is a 96% reduction in HIV transmission from an HIV-infected person to his/her sexual partner. This is seen as an argument for universal early treatment. I will not go into this further here other than to note it needs to be addressed and that the debate is happening at the global level. The question of what this means at country level for national governments in high prevalence countries is ignored. The reality in the poorer countries is national governments do what they can with what they have, (and expect donors will continue to fund existing streams of treatment, even if they are not expanded). This needs to be assessed as a matter of urgency. A key message from Dr Bertozzi of the BMGF is that we have to make choices. He suggests: “the well of treatment is infinitely deep” and if we continue drawing from it then we will have to decide which prevention activities we are going to stop.

Conclusion

In 2011 there were a number of meetings to mark the 30^th anniversary of the identification of the AIDS epidemic. It was a time of reflections and retrospection. This year will see the community pause and reinvigorate the response. The next major event on the global development calendar will be the 2015 Millennium Development Goals. These will show how devastating AIDS has been in some settings – not just slowing but reversing certain development indicators. It should be on the agenda for the Washington conference and beyond. The one thing I would like to see are pilot and trial programmes being taken to scale across nations.

Major Meetings for HEARD in 2012

March 5- 8: 19th Conference on Retroviruses and Opportunistic Infections (CROI), Seattle: a scientifically focused meeting of researchers working to understand, prevent and treat HIV/AIDS and its complications. About 4000 people and very scientific.

March 19- 20: Multi-stakeholder Consultation on National AIDS Programmes Effectiveness, Efficiency and Sustainability’, Nairobi: Partners include IAS, World Bank, PEPFAR, and UNAIDS. This is still being planned and will be a small meeting.

July 21 – 22: International AIDS Economics Network Pre-Conference Meeting, Washington DC: small but fun for economists.

July 22 – 27: XIX International AIDS Conference, Washington DC: the big event in the global AIDS calendar with many pre-meetings and side meetings.

October 31 - November 3: The Second Global Symposium on Health Systems Research, Beijing:, don’t know much about it.

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[i] Schwartländer et al, Towards an improved investment approach for an effective response to HIV/AIDS, The Lancet - 11 June 2011 ( Vol. 377, Issue 9782, Pages 2031-2041 )

[ii] See the speech by President Obama on World AIDS Day, and his commitment to put six million on treatment (up from 4 million) but no new money. The Centre for Strategic and International Studies December 2011 report How to Achieve a Successful PEPFAR Transition in South Africa is a harbinger of policy thinking. Reviewing this and other think tanks (Centre for Global Development) could provide a bellwether for trends.

[iii] See the innovative RethinkHIV for cost benefit analysis www.rethinkhiv.com

[iv] See the briefing document I prepared in November 2011, To Washington in 2012 and Beyond: Strategic Issues for the Global HIV and AIDS Response.

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Sugary soda ups risky fat deposits

By Kerry Grens

NEW YORK | Thu Jan 12, 2012 2:22pm EST

NEW YORK (Reuters Health) - Drinking a liter of regular cola every day increases the amount of fat in the liver and in the muscles and surrounding the organs in the belly, according to a new Danish study.

That kind of fat buildup has been linked in other studies to an increased risk of diabetes and heart disease.

"This study suggests that the adverse effects of sugary beverages go beyond just weight gain or fat gain. It's the gaining of the wrong fat in the wrong places," said Dr. Frank Hu, a professor at the Harvard School of Public Health, who was not involved in this study.

The researchers, led by Dr. Bjrn Richelsen at Aarhus University Hospital in Denmark asked people to drink either a liter of water, milk, diet cola or regular cola each day for six months.

The 47 people who participated in the study were all overweight or obese.

Richelsen said his team chose to study this group because they anticipated overweight or obese people would be more sensitive to dietary changes than people of normal weight.

At the end of the study the regular cola drinkers ended up with 25 percent more fat surrounding their organs, and just about doubled the amount of fat in the liver and muscle.

Such increases "are in most studies associated with an enhanced risk for developing the metabolic syndrome, type 2 diabetes...cardiovascular diseases, and non-alcoholic liver diseases," Richelsen told Reuters Health by email.

Metabolic syndrome is a group of health factors that is linked to an increased risk of diabetes, heart disease and stroke.

The type of fat Richelsen's group studied -- called ectopic fat -- is thought to be more dangerous to people's metabolic health than "subcutaneous" fat, the kind that collects under the skin.

"It is well-established that ectopic fat is 'unhealthy' and induces dysfunction of the organs involved," Richelsen said.

Hu said the results from Richelsen's experiment complement those that have surveyed people about their soda drinking habits.

"This study provides another piece of evidence to support the recommendations for the reduction of sugar-sweetened beverage consumption," Hu told Reuters Health.

DO SODA TAXES WORK?

The American Heart Association recommends drinking no more than about three cans of soda a week, while young men far exceed that, with about two cans a day on average (see Reuters Health report of August 31, 2011).

Some cities and states in the United States have batted around the idea of a tax on sugar-sweetened drinks to curb people's consumption.

Denmark has instituted a tax on sugary items, but Richelsen said it's not clear how it has impacted consumers.

One study at a hospital cafeteria found that raising the price of soda by 35 cents reduced sales by 26 percent (see Reuters Health report of June 18, 2010).

The current study, published in the American Journal of Clinical Nutrition, did not find that the cola drinkers gained more weight than the other groups.

Richelsen said it's possible that the people reduced the amount of calories they ate or drank to compensate for the extra calories in the pop.

The researchers point out in their study that the sugar in soda from Denmark is different from most sodas in the United States.

In Europe, the sweetener is sucrose, as opposed to the high fructose corn syrup used in the U.S.

"It is quite convincing from the scientific literature that it is the fructose part of the sugar molecule...that is the primary culprit in inducing fat synthesis in the liver," Richelsen said.

Given that there is extra fructose in high fructose corn syrup, Richelsen said, soda from the U.S. could lead to more pronounced problems with fat gain.

SOURCE: bit.ly/x5kwKU American Journal of Clinical Nutrition, online December 28, 2011.

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