HIV Transmission Literature: Commentary by Dr. John Bartlett -- July 2007
HIV Transmission Literature: Commentary by Dr. John Bartlett -- July 2007
Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda:a randomised trial. Lancet. 2007;369:657-666. The authors of this study investigated the potential role of male circumcision to reduce HIV incidence in men.
Methods: The study included 4996 uncircumcised, HIV-negative men age 15-49 years who agreed to HIV testing and surgery in the Rakai District of Uganda. The participants were randomly assigned to immediate circumcision or a delay for 24 months. The primary outcome was HIV incidence on the basis of HIV serology at 6, 12, and 24 months.
Results: The 24-month results showed a relative risk of 0.51 (P = .006). The 2-fold reduction was significant for the entire group, and also significant for subsets that were based on sociodemographics, behavior, and sexually transmitted diseases. There were adverse events in 3.6% receiving circumcisions, but all resolved with treatment. The post-test analysis showed that behaviors were similar in all groups. Details are provided in Table 1 .
Conclusions: The study authors concluded that male circumcision reduces the incidence of HIV infection without behavior disinhibition.
Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369:643-656. This was another randomized controlled trial of circumcision, with 2784 participants from Kisumu, Kenya, who were randomly assigned to immediate circumcision or delayed for 24 months. The study was prematurely stopped due to excessive rates of HIV infection in the control group: 4.2% vs 2.1% (P = .007). This represents a risk reduction of 53%, and the details are shown in Table 2 .
Conclusions: The study authors concluded that circumcision significantly reduces the risk for HIV transmission to young men in Africa.
Comment: There are now at least 3 trials demonstrating reductions in HIV transmission from females to males following male circumcision, with protective effects at 50% to 76%. These results are consistent with observational studies and are biologically plausible. It is noted in the discussion of the study by Bailey and coinvestigators that the assumption of a 60% protective effect could reduce the number of new HIV infections by 2 million and avert 300,000 deaths in sub-Saharan Africa over the next 10 years.
The cost analysis suggested a savings of about $2.4 million over 20 years for each 1000 circumcisions. It is noted that the adverse event rate in these 3 studies varied from 1.5% to 3.6%, but the studies were done with highly trained practitioners so that generalization of these low rates with virtually no permanent sequelae may not be appropriate. It would appear that additional studies to demonstrate efficacy are unnecessary and that the major issues are the assurance of high surgical standards, low cost, and clear understanding that the procedure reduces risk for HIV transmission, but does not eliminate it so that other precautions -- including condoms -- are still necessary. One issue concerns acceptability of circumcision, which could show great variation across African communities and might be very different in other populations, such as Southeast Asia. An additional issue concerns the value of this procedure in prevention of male-to-female HIV transmission, which is still under study.
Male Circumcision to Reduce Transmission
Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda:a randomised trial. Lancet. 2007;369:657-666. The authors of this study investigated the potential role of male circumcision to reduce HIV incidence in men.
Methods: The study included 4996 uncircumcised, HIV-negative men age 15-49 years who agreed to HIV testing and surgery in the Rakai District of Uganda. The participants were randomly assigned to immediate circumcision or a delay for 24 months. The primary outcome was HIV incidence on the basis of HIV serology at 6, 12, and 24 months.
Results: The 24-month results showed a relative risk of 0.51 (P = .006). The 2-fold reduction was significant for the entire group, and also significant for subsets that were based on sociodemographics, behavior, and sexually transmitted diseases. There were adverse events in 3.6% receiving circumcisions, but all resolved with treatment. The post-test analysis showed that behaviors were similar in all groups. Details are provided in Table 1 .
Conclusions: The study authors concluded that male circumcision reduces the incidence of HIV infection without behavior disinhibition.
Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369:643-656. This was another randomized controlled trial of circumcision, with 2784 participants from Kisumu, Kenya, who were randomly assigned to immediate circumcision or delayed for 24 months. The study was prematurely stopped due to excessive rates of HIV infection in the control group: 4.2% vs 2.1% (P = .007). This represents a risk reduction of 53%, and the details are shown in Table 2 .
Conclusions: The study authors concluded that circumcision significantly reduces the risk for HIV transmission to young men in Africa.
Comment: There are now at least 3 trials demonstrating reductions in HIV transmission from females to males following male circumcision, with protective effects at 50% to 76%. These results are consistent with observational studies and are biologically plausible. It is noted in the discussion of the study by Bailey and coinvestigators that the assumption of a 60% protective effect could reduce the number of new HIV infections by 2 million and avert 300,000 deaths in sub-Saharan Africa over the next 10 years.
The cost analysis suggested a savings of about $2.4 million over 20 years for each 1000 circumcisions. It is noted that the adverse event rate in these 3 studies varied from 1.5% to 3.6%, but the studies were done with highly trained practitioners so that generalization of these low rates with virtually no permanent sequelae may not be appropriate. It would appear that additional studies to demonstrate efficacy are unnecessary and that the major issues are the assurance of high surgical standards, low cost, and clear understanding that the procedure reduces risk for HIV transmission, but does not eliminate it so that other precautions -- including condoms -- are still necessary. One issue concerns acceptability of circumcision, which could show great variation across African communities and might be very different in other populations, such as Southeast Asia. An additional issue concerns the value of this procedure in prevention of male-to-female HIV transmission, which is still under study.
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