Abstract
HIV
Late Treatment Reduces Life Expectancy
Between 1996 and 2006, life expectancy for a study cohort of U.K. residents infected with HIV-1 who began antiretroviral therapy before their CD4 counts fell below 350 cells/mm3 increased from 15 years, from 30.0 years (on average of additional years lived after age 20) to 45.8 years. Despite this large increase, life expectancy for people with HIV still lagged behind the general population by about 13 years. Waiting to start treatment after the CD4 count dropped below 350 cells/mm3 could result in up to 16 years of lost life expectancy. Additional years of life after age 20 dropped from 53.4 for individuals who started antiretroviral therapy with CD4 counts of 200–350 cells/mm3 and decreased to 41.0 and 37.9 years, as the CD4 count at initiation of treatment declined to 100–199 and <100 cells/mm3. The study data also revealed a substantial difference in life expectancy between HIV-infected male patients and female patients: 39.5 years life expectancy for male patients and 50.2 years for female patients, as compared to a life expectancy of 57.8 and 61.6 for males and females, respectively, in the general population.
Source: May M, et al. Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study. BMJ 2011;343:d6016.
Opt-Out Consent More Acceptable Than Opt-In Method
Data to support the Centers for Disease Control and Prevention's recommendation that health care centers use an opt-out consent method for routine HIV screening come from a recent study demonstrating a 78% acceptance rate of opt-out HIV screening compared to a 63% acceptance rate for opt-in HIV screening in the emergency department of an urban hospital. The opt-out method, in which patients undergo HIV screening unless they decline, is believed to have less of a stigma associated with it compared to opt-in consent methods, in which HIV is screening is offered and patients must give their consent.
Source: White DAE, et al. Increased acceptance rates of HIV screening using opt-out consent methods in an urban emergency department. J Acquir Immune Defic Syndr 2011;58:277–282.
Postpartum Cessation of ART and the Development of Drug Resistance
Pregnant women with HIV infection may initiate antiretroviral therapy (ART) during pregnancy to prevent mother-to-child virus transmission. But women who do not qualify for ART based on treatment guidelines may opt to discontinue treatment after giving birth. ART cessation postpartum has been linked to an increased risk for the development of HIV drug resistance. A study comparing the risk of drug resistance among women taking a nelfinavir-based or nevirapine-based ART regimen during pregnancy and then stopping treatment after delivery detected resistance mutations in the viral nucleic acid sequence in 75% of women who stopped the nelfinavir-based ART compared to 50% of those who stopped nevirapine-based ART. Lamivudine resistance was significantly more common among women taking nelfinavir-based ART compared to nevirapine-based ART (75% vs 12.5%). The study also found that 50% of the women who stopped nevirapine-based ART had evidence of reverse transcriptase inhibitor resistance.
Source: Ellis GM, et al. Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum. J Acquir Immune Defic Syndr 2011;58:241–247.
Factors Affecting Linkage to Care After HIV Diagnosis
Rapid entry into medical care following a diagnosis of HIV infection can improve outcomes and contribute to better control of HIV transmission. A study of nearly 3700 persons 13 years of age or older with a new diagnosis of HIV found that 48% entered care within 3 months and 30% within 4–12 months of diagnosis. Within the first 12 months after diagnosis, 22% failed to initiate care. Overall, patients diagnosed at state mental health or correctional facilities entered care more quickly than those diagnosed in hospitals, whereas those diagnosed at county health departments tended to take a longer time to enter care compared to those diagnosed in hospitals. Men had longer intervals between diagnosis and entry into care compared to women, and the same was true for blacks compared to whites and for men who have sex with men (MSM) compared to those exposed via heterosexual contact.
Source: Tripathi A, et al. Predictors of time to enter medical care after a new HIV diagnosis: a statewide population-based study. AIDS Care 2011;23:1366–1373.
Role of Sex Hormones in HIV-Related Glucose Abnormalities
Sex hormones, including free testosterone (FT) and sex hormone-binding globulin (SHBG), appear to play a role in the pathogenesis of glucose abnormalities among HIV-infected men. This conclusion derives from a study comparing FT and SHBG levels, insulin resistance, and diabetes mellitus between HIV-infected and HIV-uninfected men. Overall, the HIV-infected men had significantly lower FT and higher SHBG levels. They were more likely to have diabetes (adjusted odds ratio 1.98) and insulin resistance [0.21 units higher mean adjusted log homeostasis model assessment-insulin resistance (HOMA-IR)]. The data revealed a correlation between lower FT and lower SHBG with insulin resistance independent of HIV serostatus.
Source: Monroe AK, et al. Sex hormones, insulin resistance, and diabetes mellitus among men with or at risk for HIV infection. J Acquir Immune Defic Syndr 2011;58:173–180.
Microbicide Gel Arm of VOICE Trial Discontinued
The Microbicide Trials Network (MTN) issued a statement explaining its decision to discontinue use of tenofovir gel in the Vaginal and Oral Interventions to Control the Epidemic (VOICE) HIV prevention trial in women. VOICE was evaluating two antiretroviral-based approaches for preventing sexual transmission of HIV: use of one of two daily drug tablets or a vaginal gel. The announcement marks the discontinuation of the vaginal gel arm of the trial and follows the finding on routine review that tenofovir gel was not effective in preventing HIV in the women participating in the study. The tenofovir only tablet approach was previously discontinued after data showed that it was no more effective than placebo in preventing HIV among women. The VOICE trial will continue to assess the safety and effectiveness of the other antiretroviral-based treatment, the oral Truvada tablet, which contains a combination of tenofovir and emtricitabine.
An article in the November 26th edition of The New York Times called this “a major disappointment for AIDS research,” expressing how unexpected this finding was since a 1% tenofovir gel microbicide yielded positive findings in the earlier Caprisa study, in South Africa, in which women who used the vaginal gel regularly had a 54% reduced risk of infection. The different outcomes do not appear to be related to differences in patient adherence alone.
Furthermore, in the news update below (Herpes Simplex Virus Infection: Topical Microbicide Prevents HSV Transmission), a single, topical treatment with 1% tenofovir gel inhibited HIV transmission by 39%.
Positive Findings in Phase 1 Trial of Rectal Microbicidal Gel
The first reported findings from a clinical trial evaluating a rectally applied topical microbicidal gel intended to inhibit mucosally mediated HIV transmission revealed high patient acceptability of treatment, no significant adverse events, and no evidence of mucosal inflammation at the treatment site. The study compared rectally applied gel containing the reverse-transcriptase inhibitor UC781 at a concentration of either 0.1% or 0.25%. Two dosing regimens were evaluated: administration of a single dose or a 7-day at-home regimen. No UC781 was detected in plasma samples. The researchers exposed patient biopsy samples to HIV ex vivo, using two titers of HIV-1, and reported marked suppression of p24 in rectal tissue exposed to 0.25% UC781, suggesting reduced HIV infectibility.
Source: Anton PA, et al. First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy. PLos ONE 2011;6:e23243.
U.S. Government Sets Goals for an AIDS-Free Generation
In a recent speech at the National Institutes of Health, Secretary of State Hillary Rodham Clinton urged global leaders to undertake a renewed effort to apply the latest scientific and medical advances toward achieving an AIDS-free generation. Secretary Clinton specifically mentioned $60 million in new U.S. funding to treat cases of early HIV infection in Sub-Saharan Africa—a region that accounts for 70% of AIDS-related deaths—to prevent progression to AIDS. She pointed out that the annual cost of anti-HIV treatment for a single infected individual in Africa has decreased to $335 in 2011 compared to $1,100 in 2004. Early medical intervention was one of three key strategies she presented; the other two being circumcision for men and broader use of antiretroviral drug cocktails for pregnant and nursing women to prevent mother-to-child HIV transmission during childbirth and breastfeeding, which accounts for 1 in 7 new HIV infections. Secretary Clinton specified a target date of 2015 for preventing mother-to-child HIV transmission.
Source: McNeil Jr DG. “Clinton Aims for ‘AIDS-Free Generation’.” The New York Times, November 8, 2011.
AMA Supports Research on Organ Transplantation Between HIV-infected Individuals
The American Medical Association (AMA) has cast its support behind efforts to amend a federal law that prohibits research on organ donation by HIV-infected individuals. Organ transplantation for HIV-infected patients may now be a viable option in the AMA's view due to advances in the medical management of HIV and in transplant outcomes. Allowing research on the transplantation of HIV-infected donor organs would enable the possibility of accepting organs from the estimated 500–600 potential HIV-infected kidney and liver donors in the U.S. each year and saving the lives of approximately 1,000 HIV-infected patients annually, according to the AMA.
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Human Papilloma Virus Infection
Vaccine Effective Against Anal Cancer in MSM
As the rate of anal cancer continues to increase, especially among men who have sex with men (MSM), vaccines to prevent human papillomavirus (HPV) infection, a major cause of anal cancer, represent a promising strategy to reverse this trend. Palefsky, et al. showed that a quadrivalent HPV vaccine (Gardasil, Merck) that targets HPV types 6, 11, 16, and 18 given to a group of MSM was safe and yielded substantial reductions in the rates of anal intraepithelial neoplasia (including grade 2 or 3 neoplasias), which precede progression to anal cancer. In this substudy of a larger double-blind trial, the researchers reported a vaccine efficacy of 50.3% against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 in the intention-to-treat group and 77.5% efficacy in the per-protocol group. HPV vaccination was also associated with reduced risk of persistent anal infection with these four HPV types: specifically, a 59.4% and 94.9% reduction for the intention-to-treat and per-protocol groups, respectively.
The November “HIV/AIDS and STD Updates” in AIDS Patient Care and STDs (2011;25:694) described good protection against anal HPV infection in women by an adjuvanted bivalent HPV 16/18 vaccine (Cervarix, GlaxoSmithKline).
Source: Palefsky JM, et al. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. NEJM 2011;365:1576–1583.
CDC Recommends HPV Vaccine for Boys
The Center for Disease Control's (CDC) Advisory Committee on Immunization Practices has recommended routine vaccination of boys 11 or 12 years old with three doses of the quadrivalent HPV vaccine (Gardasil, Merck) to protect against HPV infection and related conditions such as oral and anal cancer and to offer indirect protection of women by reducing HPV transmission.
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Herpes Simplex Virus Infection
Topical Microbicide Prevents HSV Transmission
Topical administration of a microbicidal vaginal gel containing 1% tenofovir, a reverse-transcriptase inhibitor used to prevent HIV replication, reduced sexual transmission of herpes simplex virus-2 (HSV-2) by 51%, according to the results of a recent study. A single, topical treatment with 1% tenofovir gel also inhibited HIV transmission by 39%. The researchers concluded that the intravaginal concentration of tenofovir achieved with topical administration has direct antiherpetic activity. Tenofovir has been shown to inhibit HSV replication in vitro in various cell types including human embryonic fibroblasts and keratinocytes and in human lymphoid and cervicovaginal tissue samples.
Source: Andrei G, et al. Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication. Cell Host & Microbe 2011;10:379–389.
Hepatitis C Virus Infection
All-Oral HCV Drug Regimen a Possibility?
A recent article in Nature Biotechnology (Garber K. Hepatitis C: move over interferon 2011;29:963–966) explores the opportunities and challenges facing the goal of developing an all-oral combination antiviral regimen that is able to achieve a sustained virologic response (SVR) in patients with hepatitis C virus (HCV) infection without the need for interferon-α and its debilitating side effects. FDA approval earlier this year of two direct-acting antiviral agents—telaprevir (Incivek, Vertex Pharmaceuticals) and boceprevir (Victrelis, Merck) combined with promising results from a phase 2a trial to two direct-acting antivirals from Bristol-Myers Squibb, have contributed to the promise of effective non-interferon-α containing regimens.
The author points to disadvantages of the two newly approved antivirals, including the need for interferon-α as part of a combined regimen, the side effects caused by telaprevir and boceprevir, and the fact that both drugs are only effective in patients with genotype 1 HCV and not the remaining 35% or so of HCV-infected patients. Looking forward, much hope still rides on—and much research is still needed to make possible—an “all-in-one combination pill that's taken once daily for three months and cures 90% of patients.”