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The Promise of Prevention: Male Circumcision and Microbicides

Data at the 14th Retrovirus Conference highlight the protective potential of male circumcision and, to a lesser extent, microbicides.

Worldwide, more than 4 million people are newly infected with HIV each year, highlighting the need for much stronger prevention efforts. Male circumcision and microbicides have both received media attention lately, and, as highlighted at the 14th Retrovirus Conference, the news has been great on some fronts but not as good on others. Regardless, these interventions represent major opportunities for prevention.

Male circumcision is the most exiting news in HIV prevention since the ACTG 076 results were presented more than a decade ago, showing that perinatal AZT protected against vertical HIV transmission. Three trials in South Africa, Uganda, and Kenya, involving more than 10,000 men, have now shown that circumcision can cut men’s risk for HIV acquisition by about 50% [Abstracts 155aLB and 155bLB; also see ACC Mar 19 2007]. Clearly, male circumcision is protective, but we are now faced with two questions: How do we move forward with this intervention, and what are its potential downsides?

On the microbicide front, the news has been less encouraging. As recently reported in the news media, investigators halted a phase III clinical trial of cellulose sulfate after observing a higher number of HIV seroconversions among women using cellulose sulfate than among those using placebo (ACC Feb 12 2007). Few additional details were available at the conference, but investigators did note that the excess incidence was seen at all three study sites in Africa, but not in India. We will have to wait for this summer’s International AIDS Society conference or a later report to find out more about exactly what happened in these trials.

Despite their many setbacks, microbicides continue to be investigated as an option for HIV prevention. Particularly promising is the use of antiretrovirals as microbicides. In a macaque study, tenofovir gel appeared to prevent or delay SIV infection when given prior to rectal challenge with SIV [Abstract 29]. Acyclovir may also hold promise. In a small, randomized, placebo-controlled, crossover study in Thailand, acyclovir decreased HIV vaginal shedding by a mean of 0.44 log copies/mL [Abstract 30]. Whether this reduction has clinical significance, and whether acyclovir can ultimately lower the risk for HIV transmission, remains unknown.

Another potential means of preventing HIV infection is to improve prevention and treatment of associated sexually transmitted infections. Data from San Francisco suggest that the prevalence of gonorrhea (25%) and chlamydia (18%) is exceedingly high among newly diagnosed HIV-infected men who have sex with men (MSM) [Abstract 31]. Although investigators suggested that MSM who are diagnosed with HIV using a rapid test should be treated empirically for gonorrhea and chlamydia, this proposal was met with much skepticism.

— Carlos del Rio, MD

Published in Journal Watch HIV/AIDS Clinical Care April 2, 2007

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