There was substantial emphasis on prevention at the 3rd Annual IAS meeting in Rio de Janeiro, with multiple featured presentations, oral abstracts and posters; but there was far more smoke than fire. The statistics continue to be staggering. In 2004 were 39.4 million persons living with HIV infection, 4.9 million new infections, and 3.1 million deaths [Piot P, Abstract WeSl01]. These figures are 50% higher than the 1991 projections from the World Health Organization.

One of the most striking new observations regarding transmission was the explosive epidemic of HIV in Eurasia, as reported by Chris Beyrer [IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract MoPl-02)]. This is largely a result of the “heroin highway” from Afghanistan to neighboring areas in Asia and Russia. In Russia, the number of reported cases increased from about 2,000 in 1997 to 200,000 in 2002. Longitudinal data showed that the epidemic of heroin addiction came first, followed by hepatitis C and then HIV. Most infected individuals are young men who are sexually active, leading to an increase in heterosexual transmission. An important observation by Dr. Beyrer is the fact that Afghanistan has increased its production capacity to an astonishing 430 metric tons of heroin per year. A second important observation is the lack of any federal or state programs to deal with substance abuse; the usual mechanisms (provision of clean needles, methadone or buprenophrine detoxification or maintenance programs, and other harm reduction approaches) are either nonexistent or illegal.

That said, Dr. Karium noted that 86% of HIV transmissions in the world occur as result of heterosexual contact, so sex must remain the central focus of global prevention plans [Abstract TuPI02]. The obvious solution is the promotion of condom use, but this seems to have been spectacularly unsuccessful, as group after group described repeated disappointing experiences, including less than 5% condom use in Sri Lanka, 7% among female sex workers in Nigeria, and even low use of condoms among medical students in Brazil. Particularly challenging is the observation of “secondary” transmission occurring as a result of high-level viremia associated with acute or early infection, which had previously been reported by Ron Gray of Hopkins from his discordant couple study in Rakai. These findings were reiterated at the conference [Gray R, Abstract MoFo0101]. The high viral load noted in the first several weeks after transmission accounted for approximately 40% of all transmissions in the Rakai cohort, with an efficiency that was approximately ten-fold higher than during the chronic infection phase. Patients in this early stage of infection are notoriously difficult to identify. Susan Allen from Emory reported on a similar discordant couple survey from Rwanda and Zambia [IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract MoOa0107)] and again noted relatively high rates of seroconversion (26/115 or 23%) in the first three months after initial transmission as indicated by a positive P24 antigen test combined with negative serology. Early detection is critical, but remains a major challenge.

A relatively recent observation that has now gained substantial validity is the potential role of male circumcision in preventing female-to-male infection. This was previously reported by Dr. Gray from observational data, but was the subject of an enormous study by Auvert and colleagues, who presented results of a randomized trial of circumcision in 3,273 men ages 18 to 24 who underwent serologic testing at 3, 12 and 21 months [IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract TuOa0402)]. Circumcision was associated with a 65% reduction in the rate of HIV seroconversion. There was also a surprising report on female circumcision by Stallings and Karugendo [IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract TuOA0401)]. Despite multiple reasons why this procedure might increase risk, their observational data found an unanticipated 50% reduction in transmissions among circumcised women. This observation remained unexplained, but statistically significant.

A potentially important presentation on prevention was a report by A. Telenti from Switzerland who studied a cohort of sex workers in Kenya. Participants had repeated HIV exposure through unprotected sex over a period of ten years, but never seroconverted [Abstract TuPl02]. The presentation included some family trees that demonstrated a genetic pattern of nonsusceptibility. On the basis of these observations, Dr. Telenti is now developing a “genetic propensity index” in the hopes of defining the components of the immune system that appeared to be protective.

Summary

The presentations on prevention at the 3rd IAS Conferences highlighted the following:

• An explosive epidemic of HIV associated with injection drug use in Russia, with no clear national plan for how to deal with it.

• A disappointing record for condom use in multiple resource-limited countries.

• Male circumcision is now added to the list of interventions with verified benefit.

• Further studies show that prevention programs need to deal with the high rates of transmission that occur during acute infection, preceding seroconversion.

• Not surprisingly, the risk of HIV appears to be related to genetic susceptibility.

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