The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics: risk for HIV drug resistance

This study examines the potential effects of microbicide use in preventing HIV infection and transmission. Researchers used a 10 year epidemiological model simulation to predict the effects of an antiretroviral-based microbicide public health intervention. Microbicides are being developed as a tool to prevent infections in women and to empower women. Paradoxically, the researchers found that the ARV-based microbicides may benefit men more than women and that this effect will be exacerbated if high-risk microbicides are used.

The same number of infections will be prevented whether the microbicide is high-risk or low-risk. However, low risk microbicides will generate fewer resistant cases, even if adherence is high. If resistance does emerge as a result of ARV-based microbicides, the resulting strains will only be resistant to the specific class of drugs in the product. Therefore, therapeutic options, including other classes of ARVs, for the individuals who acquire resistance will be reduced but not eliminated. Prevalence of resistance would be greatest in women (22% median; IQR 8-50%), but transmitted resistance would be 12 times greater in men (2.6% median; IQR 0.8-7%) than women. The researchers recommend monthly monitoring for seroconversion. However, they also found that although the monthly tests decrease the risk to participants during the trial, the use of microbicides increases resistance in the general population when frequent testing does not occur.

Wilson DP, Coplan PM, Wainberg MA, et al. The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics. Proc Natl Acad Sci U S A 2008;105(28):9835-40. Epub 2008 Jul 7.

Alcohol abuse and dependence has big impact on cirrhosis in HIV/HCV coinfection

Researchers discovered that alcohol abuse and dependence significantly increases the risk of advanced fibrosis/cirrhosis among those with HIV, HCV and HCV/HIV coinfection. However, this effect was not observed in lesser degrees of alcohol consumptions, which were defined by NIAAA criteria. The study, Veterans Aging Cohort Study (VACS), was a longitudinal study of 6,090 age/sex matched HIV+/HIV- U.S. Veterans at 8 sites. Of the 4,678 veterans with complete data, 425 (9.1%) had advanced fibrosis/cirrhosis. This number includes 12.5% of the HIV+ and 4.4% of HIV- subjects. Researchers discovered a trend towards increased liver injury with hazardous or binge-drinking. However, they only observed a statistically significant increase in advanced fibrosis/cirrhosis in those with an IDC-9 diagnosis of alcohol abuse and dependence (AAD). Among these were 9.5% of the HIV infected, 15.6% of the HCV infected and 33.1% of the HCV/HIV co-infected. In multivariate analysis, after controlling for HCV and HIV, alcohol was the strongest correlate of advanced fibrosis/cirrhosis. Other significant correlates include age > 50 years, black race and HBV. Of the subjects with advanced fibrosis/cirrhosis, 38.7% had a diagnosis of ADD. Thus, the conclusion of the study is that alcohol abuse and dependence is particularly common among individuals with advanced fibrosis/cirrhosis.

Lim JK, Fultz SL, Goulet JL, et al. Impact of Alcohol Abuse and Dependence On Liver Fibrosis in a Prospective Cohort of 6090 HIV+/Hiv- U.S. Veterans. Digestive Disease Week. San Diego, CA May 17-22, 2008

Role of week 4-rapid virological response (RVR) in prediction of sustained virological response to Peg-IFN plus ribavirin in HCV/HIV co-infected individuals

This study was performed as a retrospective review of two prospective, open-label single center studies in HCV/HIV co-infected patients who attended a specialty outpatient clinic in Dublin, Ireland. The objective of the study was to evaluate the role of rapid virological response (RVR) in predicting sustained virological response (SVR) rates to hepatitis C virus (HCV) therapy. Virological response was assessed at four intervals: week 4 (RVR), week 12 (EVR – early virological response), week 24 (EOTR – end of treatment) and 24 weeks post-completion of treatment (SVR). The researchers discovered that the achievement of RVR, a negative HCV-PCR, at week 4 of treatment is indeed predictive of SVR in this cohort of patients. The positive predictive value of RVR at week 4 for subsequent SVR in HIV-HCV co-infected patients was 100%, while the negative predictive value was 57%. Sixty percent of the 65 patients achieved SVR (25% genotype 1 / 4, 77% genotype 2 / 3). The significant variables associated with SVR were lower median pre-treatment HCV viral load, genotype 2 / 3 disease and achievement of RVR. The researchers suggest that with this evidence, it would be possible to identify, based on their HCV-PCR test at week four, which of the patients would only need 6 months of a full dose to achieve SVR. In addition, these findings further strengthen the groups previously published recommendation to individualize the duration of HCV therapy for HIV/HCV co-infected patients.

Shea D O, Tuite H, Farrell G, et al. Role of week 4-rapid virological response (RVR) in prediction of sustained virological response to Peg-IFN plus ribavirin in HCV/HIV co-infected individuals. Journal of Viral Hepatitis 2008;15(7):482-89.

Randomized comparison of 12 or 24 weeks of peginterferon a-2a and ribavirin in chronic hepatitis C virus genotype 2 / 3 infection

Researchers discovered that the effectiveness of 12 weeks of combined peginterferon a-2a and ribavirin treatment is inferior to 24 weeks in patients infected with genotype 2 or 3. The study followed 382 genotype 2 / 3 infected patients at 31 centers in Denmark, Finland, Norway, and Sweden who were randomly selected for 12 or 24 week therapy. The sustained viral response (SVR) rates, 59% (12 week) and 78% (24 week), were significantly greater for those who were treated longer, regardless of fibrosis stage and genotype. In addition, 12-week patients experienced a higher relapse rate (33% versus 12%) than 24-week patients.

Post hoc analysis identified two groups of patients who responded favorably to short-term treatment; patients younger than 40 years who have achieved RVR and those 40 years or older with very rapid virological response, meaning HCV-RNA below 1000 IU/mL on day 7 in addition to achieving RVR. Age was determined to be a significant factor on the efficacy of treatment. Patients younger than 40 years of age had decidedly better outcomes than those 40 and over. Thus, if patients with favorable viral kinetic response to therapy were selected for 12 weeks of therapy, and the demographics were similar to those in the study, 40% of the total population would be suitable for short-term therapy, which would lead to a 20% reduction in pharmaceutical costs as well as a substantial reduction in side effects along with minimal change of SVR rates.

Findings from this study differ from previous reports on treatment shorter than 24 weeks for patients with these genotypes. Possible explanations of this difference include a greater proportion of unfavorable prognostic features included in this study population, differences in ribavirin dosage, and differences in treatment duration.

Lagging M, Langeland N, Pedersen C, et al. Randomized comparison of 12 or 24 weeks of peginterferon a-2a and ribavirin in chronic hepatitis C virus genotype 2 / 3 infection. Journal of Hepatology. June 2008.

Khorrami, Pollard & Abir Files Class Action Civil Rights Lawsuit in Federal Court Against California Prisons for Failure to Properly Treat Inmates With Hepatitis C

The law firm of Khorrami, Pollard & Abir filed a class action law suit in Los Angeles on July 8 contending that the California Department of Corrections and Rehabilitation (CDCR) is unjustly excluding thousands of inmate from liver biopsies and hepatitis C anti-retroviral treatment, allowing them to progress to more advances stages of liver damage. The suit sites the fact that the standard of care as set by the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) requires that patients with Stage II Hepatitis be offered treatment. Contrary to this standard, the CDCR requires inmates to develop a more advances stage of hepatitis C before they are willing to initiate treatment. Without Stage II treatment the likelihood of developing cirrhosis, liver failure, and liver cancer dramatically increases. The case was filed on behalf of Kevin Johnson, the lead plaintiff and a current inmate at California State Prison at Solano. It names the defendant as Robin Dezember, the director of the division of health services responsible for the health care policies for the CDCR.

"Despite an established standard of care, the California Department of Corrections and Rehabilitation has adopted protocols designed to exclude patients from diagnostic biopsies and treatment. This is in contrast to the care and treatment provided to the general population," says Khorrami. "This practice not only denies inmates proper care and allows their health to deteriorate, but also presents a health danger of further spreading the disease not only within the prison population but also in the general population once the infected inmates are released from prison."

Marketwire-July 8, 2008. Accessed 22 July 2008. Available at: http://www.marketwire.com/press-release/Khorrami-Pollard-and-Abir-Llp-876713.html

Compiled by Alyssa Sankin