CROI Conference, Denver, CO February 8, 2006 (cont.)
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.
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.