Update #3, Wednesday, February 8 from the Retroviruses and Opportunistic Infections, National Meeting

Conference - February 8, 2006 Transcript

Dr. Eric Daar offers perspectives of interest on topics from the 13th Conference on Retroviruses and Opportunistic Infections (held in Denver, Colorado February 5-8, 2006)

This is a report from the final day of the 13th Conference on Rotaviruses and Opportunistic Infections in Denver, Colorado. There were numerous presentations particularly related to complications of antiretroviral therapy and novel and emerging treatments. I will focus on these topics along with select epidemiologic studies.

Circumcision and HIV Transmission

A Plenary presentation by Tom Quinn from the National Institutes of Health and Johns Hopkins University provided an overview on the background and rationale for considering the role of male circumcision as a strategy to reduce HIV transmission. He summarized that there are numerous factors that determine the infectiousness of an HIV-infected individual. He commented that person's viral load as well as viral load in genital secretions, along with the presence or absence of circumcision, the stage of their clinical disease, the presence of genital ulcers or other sexually transmitted diseases, cervical pathology, certain other characteristics of a given strain of HIV and even the use of antiretroviral therapy may influence infectiousness. Factors that might increase the risk for someone to acquire HIV include the viral load in blood as well as genital secretions of their sexual partner, the presence or absence of circumcision, genital ulcers, sexually transmitted infections, cervical pathology, as well as genetic factors. He provided some history and perspective on circumcision, including medical benefits such as lower risks of cervical cancer amongst partners of men who have been circumcised as well as a reduced risk of penile cancer and localized infections, both sexual and otherwise in those who have been circumcised.

In a variety of epidemiologic studies looking at communities in which circumcision is common (greater than 80 percent) verses uncommon (less than 20 percent, it has been shown that circumcision is associated with low frequency of HIV infection. There was a pivotal study from Rakai published in the New England Journal several years ago by Tom Quinn and his colleagues showing that viral load was an important predictor of HIV transmission amongst discordant couples. They also noted that independent of viral load amongst 50 individuals in which the male partner was circumcised, there were no cases of transmission. A potential biologic explanation includes the fact that many target cells for HIV infection are present under-surface of the foreskin which otherwise are not present in circumcised individuals. Ultimately this led to the initiation of 3 randomized controlled trials, one in South Africa, another in Uganda and Kenya. These communities have populations with a low frequency of circumcision and were randomly assigned to circumcision or no circumcision. Recently, the report from one of these 3 trials, all of which include over 2500 to 5000 patients, was reported when the data safety monitoring board terminated the trial because it found circumcision to be clearly associated with lower risk of transmission. This study was looking at the risk for men to acquire infection from women; with more information is needed from the other trials to confirm these findings as well as to assess the effect on transmission to women.

Tolerability of Antiretroviral Therapy in the Developing World

There were two important studies presented by the CDC, one in Uganda and one in Nairobi, looking at the side effects associated with the roll-out of antiretroviral therapy in the developing world. The largest of the two studies was from Uganda where they looked at 1000 patients between 2003 and 2004- about 75% women who were treated as part of a home-based AIDS care program with mostly D4T, 3TC and nevirapine- a common regimen used in the developing world. The investigators followed these people for the development of toxicities and found that peripheral neuropathy was seen in about 36%, 10% being severe, with rash in 6%, 2% being reported as severe. In addition, 2% of subjects developed hypersensitivity reaction (presumably to nevirapine). Overall, up to 40% of the patients in this group developed some toxicity, 14% being severe. Therefore, while there are clear clinical benefits that are going to be associated with the roll-out of therapy, it will be important to monitor for toxicities to assure patient safety.