AIDS PATIENT CARE and STDs Volume 25, Number 3, 2011 Mary Ann Liebert, Inc. DOI: 10.1089/apc.2011.

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UPDATES

HIV/AIDS and STD Updates

New HIV Prevention Guidelines from the CDC The Centers for Disease Control and Prevention (CDC) has issued an interim guidance on the use of a dual-drug preexposure prophylaxis strategy to prevent HIV infection in men who have sex with men (MSM). Surveillance data suggest that HIV infections have been increasing among MSM for the past 15 years. The guidance was based on the results of the Pre-Exposure Prophylaxis Initiative (iPrEX) study, announced in November 2010, which evaluated the safety and efcacy of preexposure prophylaxis (PrEP) among exposed but uninfected MSM. The phase 3, randomized, double-blinded, placebo-controlled trial compared daily use of the oral antiretroviral agents tenofovir disoproxil fumarate (TDF) and entricitabine (FTC) to placebo, in combination with standard behavioral interventions. Subjects in the PrEP arm had a 44% reduction in HIV acquisition, and this gure rose to 50% among subjects with 50% or more adherence. Based on the positive study results, the CDC is developing guidelines on the use of PrEP for MSM at high risk of HIV acquisition. Until trials currently underway to assess the safety and efcacy of PrEP in individuals at high risk for HIV infection via other routes of transmission are complete, the CDC recommends that PrEP only be considered in the MSM population. As the prophylactic benet of a daily TDF/FTC regimen varied with adherence, the CDC emphasizes the importance of support and monitoring to maximize adherence to the prescribed medication regimen. Identifying MSM who are most likely to benet from PrEP are those at high risk for HIV infection who routinely follow proven risk-reduction measures such as condom use. In the multinational iPrEX study, uninfected men at high risk for HIV infection due to unsafe sexual behaviors took either a combined formulation of 300 mg TDF and 200 mg FTC or placebo. The participants were evaluated every 3 months for an average follow-up period of 1.2 years, and up to 2.8 years. All subjects received regular monitoring of HIV status, risk-reduction counseling, and medication adherence support. The PrEP regimen was associated with HIV risk reduction ranging from 21% among subjects with less than 90% medication adherence to 73% among those with 90% or more adherence. Drug level testing in HIV seroconverters and a matched group of uninfected subjects revealed a 92% reduced risk for HIV acquisition among subjects with detectable levels of TDF/FTC compared to those with no detectable drug. The Interim Guidance was published in the January 28, 2011 issue of MMWR. The February 2011 issue of AIDS Patient Care & STDs features a review of the PrEP, highlighting its promises and pitfalls (2011;25:6371). Vaccine Effective Against HPV Infection in Males Results of a phase 3 trial of the quadrivalent anti-HPV vaccine Gardasil (Merck, Whitehouse Station, NJ) in 4065 males ages 1626 years showed the vaccine to be effective in at reducing the numbers of external genital lesions among HPVinfected subjects and in preventing anogenital HPV infection. In boys and men with either positive or negative HPV status at baseline, the vaccine was 60.2% more effective than placebo in preventing external genital. This gure increased to 65.5% for HPV-6, - 11, - 16, or - 18related lesions. Among the subgroup of study participants that were HPV-negative at enrollment, the vaccines efcacy rose to 90.4% among HPV6, - 11, - 16, or - 18 lesions. Initially introduced as a vaccine to protect against HPVrelated disease including cervical cancer and genital warts, Gardasil has more recently received approval for the prevention of anal cancer in males and females aged 926 years. The study was published in the New England Journal of Medicine 2011;364:401411. Stroke Risk Increases with HIV Antiretroviral therapy (ART) may increase stroke risk. A review of epidemiologic data designed to identify trends in stroke and comorbid HIV infection during the 10-year period 1997 to 2006 revealed that the proportion of patients hospitalized for stroke (ischemic or hemorrhagic) who were HIV positive increased signicantly from 0.09% in 1997 to 0.15% in 2006. Even as the number of hospitalizations for stroke in the United States decreased by 7% during this period, the number of patients hospitalized for stroke with comorbid HIV infection increased by 60%. While the percentage of ischemic stroke patients with comorbid HIV infection increased signicantly (0.08% in 1997 versus 0.18% in 2006), there was not a signicant change in HIV infection rates among patients with hemorrhagic stroke. The study was published in Neurology 2011;76:444450. Tuberculosis Protection Before and After Exposure Tuberculosis (TB) is one of the leading causes of death among people infected with HIV. In 2008, TB accounted for 23% of AIDS-related deaths worldwide. In countries with relatively high HIV prevalence, up to 80% of people with TB test positive for HIV, according to the World Health Organization. Approximately 30% of HIV-infected persons globally are estimated to have latent TB infection. The multistage tuberculosis vaccine called H56 was designed for both prophylaxis against TB infection and to combat TB postinfection. The H56 vaccine combines the early-stage antigens Ag85B and ESAT-6 with the latencyassociated protein Rv2660c, which is expressed during later stages of infection. A study conducted in mouse models of tuberculosis has shown that H56 can confer protective immunity in preexposure animals. H56 vaccination in

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202 mouse models of latent tuberculosis was associated with better control of disease reactivation and signicant reductions in bacterial load compared to adjuvant-treated control mice. The vaccine provided better containment of late-stage infection than vaccines designed to target only early antigens. The study was published in Nature Medicine 2011;17:189 194. WOMEN AND HIV/AIDS Higher Pregnancy Incidence and Poorer Outcomes among HIV-Infected Youths Young women who are HIV positive tend to have high pregnancy rates compared to the general youth population. They also tend to have poorer pregnancy outcomes, with a greater risk of premature births and spontaneous abortions. A retrospective study conducted over a 12-year period among young women aged 1324 years compared pregnancy incidence and outcomes among youths who became infected with HIV as a result of risky behaviors (behaviorally infected youths, or BIY) to those infected at birth (vertically infected youths, or VIY). The results showed that BIY had signicantly higher pregnancy rates than VIY: 74.5% BIY versus 21.5% VIY had one or more pregnancies during the study period. The BIY group was more likely to have more than 1 pregnancy (36.8% BIY versus 14.3% VIY). Incidence of pregnancy among behaviorally infected youths was 2.5 to 5 times greater than among youths without HIV infection. The study was published in JAMA 2011;305:468470. Clinical Outcomes in HIV Infection Vary with Gender, Race, and Geography Gender, race, and geographic region contribute to differences in symptoms, morbidity, and use of antiretroviral therapy following primary HIV infection. In a study of 2277 seroconverters, women tended to have fewer initial symptoms, lower viral loads, and higher CD4 + cells at diagnosis compared to men. Over time, however, women tended to fare worse as a group, with greater than twofold more HIV-related morbidity than men. The study found higher morbidity for nonwhite women than white women. Individuals from southern regions of the United States, and particularly non-white southerners, had greater HIV-related morbidity. The authors propose that gender and race differences in HIV-related morbidity are primarily a reection of socioeconomic factors. With regard to ART use, women began ART sooner than all other study groups, while southerners and non-whites tended to being ART later. Neither gender nor race was associated with differences in ART response. The study was published in the Journal of Infectious Diseases 2011;203:442451. HEPATITIS C VIRUS Introduction The CDC estimates that approximately 3.2 million people in the United States are chronically infected with hepatitis C virus (HCV), making it the most common chronic bloodborne

HIV/AIDS AND STD UPDATES infection in the United States. An estimated 170200 million people have chronic HCV infection worldwide. At least 50% and as many as 90% of HIV-infected injection drug users are also infected with hepatitis C according to CDC estimates. Telaprevir Earns Priority Review Status Telaprevir, an oral inhibitor of hepatitis C virus being developed by Vertex Pharmaceuticals, received Priority Review status from both the U.S. FDA and Health Canada. This follows on the heels of acceptance of telaprevir by European Union drug regulatory authorities for Accelerated Assessment. Priority Review in the United States will allow for an accelerated 6-month process, with a target FDA review date of May 23, 2011. In Canada, telaprevir could complete the review process within approximately 69 months. Telaprevir inhibits an HCV protease, thereby interfering in viral replication. Vertex has submitted data from three phase 3 studiesADVANCE, ILLUMINATE, and REALIZEthat demonstrate higher viral cure rates for combination therapy with telaprevir, pegylated-interferon alfa-2a, and ribavirin compared to available drugs. New Treatments for Hepatitis C Virus Dr. John Ward, director of the Division of Viral Hepatitis at the CDCs National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, recently told a group of health journalists, We are on the cusp of a revolution in hepatitis C treatment. Before 2011 comes to a close, two new anti-HCV drugs could receive FDA approval. When given in combination with the existing drugs pegylated-interferon alfa-2a or alfa-2b and ribavirin, these new drugs have been shown to increase cure rates. Furthermore, new HCV screening guidelines are expected from the CDC, which estimates that approximately 3.2 million persons in the United States have chronic HCV infection, although many are unaware they carry the virus. In January, Mercks oral HCV protease inhibitor, called boceprevir, was awarded FDA Priority Review and EMA Accelerated Assessment. Merck has reported phase 3 trial data that demonstrate signicantly higher sustained virologic response (SVR) rates with boceprevir (as part of a tri-drug regimen) in both adults who have failed or are new to treatment, compared to a dual-drug regimen. Vertex Pharmaceuticals oral HCV protease inhibitor, telaprevir, has also received Priority Review and Accelerated Assessment status. In phase 3 trials in treatment-nave patients, combination therapy with telaprevir achieved viral cure in 75% of patients, compared to 44% in patients given the existing two-drug therapeutic cocktail. Vertex also reported evidence to support viral cure in half the time needed with conventional treatment. Source: CDC HIV/Hepatitis/STD/TB Prevention News Update Note At least 1 in 4 HCV-infected individuals in the United States do not know their status. With the development of more effective HCV treatments it will become increasingly important to identify infected persons and offer them treatment, as discussed in a paper by Swan and colleagues in the December 2010 issue of AIDS Patient Care & STDs (2010;24:753762).

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