Abstract
HIV
Shift in Cancer Types Seen in HIV-Infected Population
The types of cancer affecting HIV-infected individuals in the United States is changing, mainly due to an increase in the number of older HIV-positive Americans, which is a result of the success of antiretroviral therapy, making it possible for people to live longer with HIV/AIDS. A group of researchers from the National Cancer Institute (NCI, Bethesda, MD) and the Centers for Disease Control and Prevention (CDC, Atlanta, GA), linked data from HIV and cancer registries in the United States from the time period 1991–2005 to explore trends in cancer prevalence among HIV-infected individuals. They estimate that the number of AIDS-defining cancers (i.e., Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer) decreased by greater than threefold over the 15-year period, while non-AIDS–defining cancers increased by approximately threefold. During the study period the U.S. AIDS population grew by approximately fourfold, with the greatest increase among people aged 40 years or older. Among the non-AIDS–defining cancers, those estimated to have increased include anal, prostate, and lung cancers, and Hodgkin's lymphoma.
Source: Shiels MS, et al. Journal of the Natinall Cancer Institute, April 11, 2011. DOI:10.1093/jnci/djr076
Early End for FEM-PrEP HIV Prevention Trial
A review of interim data from the FEM-PrEP (pre-exposure prophylaxis) trial led Family Health International (FHI) to conclude that the trial is unlikely to demonstrate the effectiveness of Truvada (Gilead Sciences, Foster City, CA) in preventing HIV infection among a group of women in Kenya, South Africa, and Tanzania. As a result, FHI announced plans to close the trial ahead of completion. The study is designed to compare the prophylactic effect of Truvada, a once-daily pill containing a combination of emtricitabine and tenofovir, in women randomly assigned to either a treatment or placebo group. The interim data revealed a new HIV infection rate of 5% per year among the trial participants, with an equal number of infections developing among women receiving Truvada or placebo, a result FHI describes as “surprising and disappointing.” This outcome is in contrast to previous positive findings for Truvada as a PrEP agent in men who have sex with men. FHI will continue to analyze the current study data and blood specimens to identify factors contributing to the unexpected outcome. Despite self-reported adherence to medication use of approximately 95% among study participants, FHI will explore the possibility that low adherence to the study regimen contributed to the results, or whether the negative outcome is due to a true lack of drug effectiveness.
Source: FHI Statement on the FEM-PrEP HIV Prevention Study.
HIV RNA Levels in Genital Secretions Predict Sexual Transmission Risk
High levels of HIV RNA in genital secretions—endocervical samples in women and semen samples in men—correlate with an increased risk for heterosexual transmission of HIV. Measures of HIV RNA in genital secretions represent a useful biomarker for risk assessment independent of plasma HIV RNA levels. This finding derives from a prospective study of more than 2500 couples in Africa, among which one partner was HIV positive at the outset of the study. The results support a correlation between genital and plasma HIV RNA concentrations, and demosntrate that genital HIV RNA measures alone can independently predict heterosexual HIV transmission risk.
Source: Baeten JM, et al. Science Translational Medicine 2011;3:77. DOI:10.1126/scitranslmed.3001888
ATS Workshop Focuses on Controversies in HIV-Associated Lung Disease
The American Thoracic Society (ATS) published an official report on a workshop entitled “Emerging Issues and Current Controversies in HIV-Associated Pulmonary Disease,” focusing on lung disorders associated with morbidity and death in individuals with HIV/AIDS. Whereas the main lung diseases affecting HIV-infected patients early on were opportunistic pneumonias, such as tuberculosis, bacterial pneumonia, and Pneumocystis pneumonia, with the success of antiretroviral therapy and HIV becoming a chronic disease, the importance of noninfectious pulmonary diseases has increased, including lung cancer, chronic obstructive pulmonary disease, and pulmonary arterial hypertension. Topics discussed include HIV replication in the lung, and the effects of HIV on pulmonary immunity and susceptibility to infection, including Mycobacterium tuberculosis and nontuberculous mycobacterial disease, and fungal pneumonias.
Source: Morris A, et al. The Proceedings of the American Thoracic Society. 2011;8:17–26.
Children with Perinatal HIV Infection are Surviving to Adolescence
Effective antiretroviral treatment has made it increasingly commonplace for children with perinatally acquired HIV infection to survive into their teenage years and beyond. Data from the Pediatric HIV/AIDS Cohort Study AMP Protocol, an ongoing prospective multicenter study conducted at sites across the United States, indicate that most children with perinatal HIV who are on ART regimens are able to maintain low viral loads and good CD4 values. The earlier that treatment is initiated in these patients, the better the immune outcomes. The study population comprised a group of children ages 7 to 16 years. The results indicated that 78% had a CD4% greater than 25% and 68% had a suppressed viral load. Younger age at initiation of ART, suppressed viral load, and a higher nadir CD4% were significant, independent predictors of a higher CD4%.
Source: Van Dyke RB, et al. Journal of Acquired Immune Deficiency Syndromes 2011. DOI:10.1097/QAI.0b013e318215c7b1
HIV Antiretroviral Prophylaxis is Safe and Effective During Breastfeeding
A change in World Health Organization (WHO) guidelines recommending antiretroviral prophylaxis during breastfeeding—given to either the mother or the baby—reflects recent study results demonstrating the safety of ART and its effectiveness in preventing mother-to-child transmission of HIV during pregnancy and breastfeeding. The Kesho Bora Study Group evaluated the prophylactic efficacy and safety of a triple antiretroviral regimen administered to HIV-positive pregnant women beginning at 28–36 weeks of gestation and continued until cessation of breastfeeding, up to a maximum of 6.5 months after delivery. The regimen comprised a combination of 300 mg zidovudine, 150 mg lamivudine, and 400 mg lopinavir, plus 100 mg retonavir twice daily. A second group of HIV-positive pregnant women received only 300 mg zidovudine twice daily until delivery, followed by 600 mg zidovudine plus 200 mg nevirapine at the onset of labor, and 300 mg zidovudine plus 150 mg lamivudine twice daily for one week after delivery. The babies of all treated mothers received a 0.6 mL dose of nevirapine at birth and 4 mg/kg zidovudine twice daily for one week after birth. At 6 weeks postpartum, the rate of HIV transmission was 3.3% in the triple antiretroviral group, compared to 5.0% in the zidovudine/single-dose nevirapine group. The rates of HIV transmission at 12 months were 5.4% and 9.5%, respectively. Among women who intended to breastfeed, 12-month HIV transmission rates were 5.6% for the triple antiretroviral group and 10.7% for the zidovudine/nevirapine group.
Source: The Kesho Bora Study Group. The Lancet Infectious Diseases 2011;11:171–180.
Hepatitis C Virus
New Combination Drug Treatment for Hepatitis C Shows Early Success
A dose-escalation trial involving 88 patients with chronic hepatitis C virus (HCV) infection in Australia and New Zealand generated promising results for an oral combination treatment that includes two experimental anti-HCV drugs: RG7128, a nucleoside polymerase inhibitor; and danoprevir, an N53/4A protease inhibitor. Study participants in this double-masked study were randomly assigned to receive up to a 13-day combination regimen of RG7128 (500 mg or 1000 mg twice daily) and danoprevir (100 mg or 200 mg 3 times daily, or 600 mg or 900 mg twice daily), or placebo. The results indicate that 2 weeks of treatment at the highest combination doses yielded substantial decreases in HCV RNA concentration, compared to an increase in HCV RNA in the placebo group. Interferon, the current standard of care for chronic HCV infection—administered via weekly injections and twice daily pills for up to 48 weeks—is associated with often debilitating flu-like side effects, a common reason for patients to stop or decline treatment. In contrast, this new combination regimen was well tolerated, with no reported serious adverse effects or treatment-related safety issue. According to one of the study authors, the new treatment may be up to 80% effective, which compares to the 50% cure rate achieved with interferon.
Sources: Gane EJ, et al. The Lancet 2010:376:1467–1475; The Age. March 15, 2011 (
FDA Advisory Committee Reviews Safety of Boceprevir
Materials prepared in advance of an Antiviral Drugs Advisory Committee meeting summarize the FDA's safety concerns regarding boceprevir, a protease inhibitor developed by Merck & Co. for the treatment of hepatitis C virus infection in adults. The FDA describes the most important safety concern as the increased frequency of anemia in patients receiving boceprevir in combination with peginterferon alfa and ribavirin above and beyond the decreased hemoglobin levels previously reported with peginterferon and ribavirin alone. This finding, combined with an increased frequency of neutropenia and thrombocytopenia, suggests that boceprevir exerts an overall bone marrow suppressive effect. The other main safety issue relates to the higher numbers of patients treated with boceprevir in clinical trials that reported psychiatric symptoms of suicidal and homicidal ideation compared to control subjects. Such psychiatric adverse events have also been linked to treatment with pegylated interferon and the added risk of combining these medications is unclear.
Source: Food and Drug Administration,