Cortlandt Forum correspondent Kevin J. Armington, MD, reports on highlights from the 16th Annual Conference on Retroviruses and Opportunistic Infections (CROI), which took place recently in Montreal.
The CDC recently revised upward the estimates of annual HIV incidence from 40,000 to 50-60,000. Clearly, behavioral strategies and educational campaigns are not curbing the number of new infections. This has generated deep interest in pharmacologic approaches to preventing HIV transmission. A number of interesting approaches that seek to inhibit sexual HIV transmission are under investigation and some encouraging results were reported at the 16th annual Conference on Retroviruses and Opportunistic Infections (CROI).
Use of oral antiretroviral agents to prevent infection has become standard of care for health-care workers who suffer occupational exposure to HIV and for individuals who present within 72 hours of sexual exposure. Another strategy utilizes pre-exposure prophylaxis (PrEP) dosing with a virucidal topical agent or oral antiretroviral medication. Several studies at CROI reported encouraging results of early PrEP studies. Additionally, there is evidence that HIV-positive patients with a suppressed viral load are less likely to transmit to their partners. Here's a rundown.
- Dobard et al. tested topical gels containing tenofovir or tenofovir plus emtricitibine applied intravaginally in 23 female pigtail macaques exposed intravaginally with simian HIV twice weekly. Control arms utilized a placebo gel or no gel. The macaques were dosed with the topical gel 30 minutes prior to intravaginal viral exposure. None of the animals who received tenofovir (n=6) or tenofovir/emtricitabine (n=6) gel became infected after 20 challenges whereas 2/2 in the no gel and 8/9 in the placebo gel arms became infected, following a median of four challenges. The authors concluded that both gels conferred consistent protection and suggest that tenofovir gel may represent a “very effective strategy” for human trials. (Dobard C, Parikh U, Sharma S et al. Complete protection against repeated vaginal simian-HIV exposures in macaques by a topical gel containing tenofovir alone or with emtricitabine. Abstract 46, 16th CROI, Montreal, 2009.)
- At CROI 2008, a large trial of the microbicide cellulose sulfate was reported to be associated with an increased risk of HIV transmission among uninfected women who used the topical agent. Some participants were concerned that the results would significantly slow momentum for development of other topical preparations, which many feel are needed to place an HIV prevention tool directly in the hands of women. Interest in microbicides may be rekindled after presentation of a “late breaker” paper detailing results of a four arm, randomized, placebo-controlled trial that recruited over 3,000 HIV-negative women. Two experimental gels were compared to placebo gel and no gel. Over an average of 20 months, one of the experimental gels, Pro 2000/5, which contains naphthalene, was associated with a 30% reduction in HIV transmission while the second gel, known as BufferGel, did not decrease transmission. However, the reduction in HIV acquisition associated with Pro2000/5 was not statistically significant in an intent-to-treat analysis. Both experimental products were found to be safe. The findings are modest but likely to increase interest in anti-HIV topical microbicides. (Karim SA, Coletti A, Richardson B, et al. Safety and effectiveness of vaginal microbicides BufferGel and 0.5% PRO 2000/5 gel for the prevention of HIV infection in women: Results of the HPTN 035 Trial. Abstract 48LB, 16th CROI, Montreal, 2009.)