Commentary from the CDC HIV/STD/TB Prevention News Update 12/03/02:
STDs, co-factors in HIV transmission, are quite prevalent in sub-Saharan Africa. Two community-based trials have tested the notion that improved treatment of STDs may be a strategy for HIV prevention. Over a two-year period, improved clinical management of symptomatic STD treatment in Mwanza, Tanzania, showed a reduction of 38 percent in HIV incidence. Over the same interval, with comparable proportional reductions in the treated STDs, periodic mass treatment in Rakai, Uganda, did not reduce the incidence of HIV.
One explanation for the discrepancy in these two trials is that STD co-factors may play a larger role in early, concentrated HIV epidemics, such as the one in Mwanza, and a lesser role in mature epidemics such as the one in Rakai. Early in HIV epidemics, infections occur in a core group of highly sexually active individuals, who have high rates of STDs. As an epidemic progresses, more HIV transmissions occurring in stable relationships with lower prevalences of STDs. In addition, as a result of selective HIV-attributable mortality among high-risk individuals, STD prevalences decline.
The authors noted that previous model-based studies of the decreasing importance of STD co-factors during an HIV epidemic did not account for two key factors: a high rate of herpes simplex virus type 2 (HSV-2), which enhances AIDS transmission; and reductions in sexual risk behavior.
The current study assessed how the impact of STD treatment on HIV transmission would vary over time in an HIV epidemic, taking into account the role of HSV-2 and behavioral change, using the transmission model STDSIM. (STDSIM simulates the natural history and transmission of STDs and HIV in a dynamic population of interacting individuals.)
Researchers simulated the spread of curable STDs, HSV-2, and HIV, quantifying parameters to represent the severe HIV epidemic in Rakai, using demographic, behavioral, and epidemiological data from the STD treatment trial and preceding cohort data. Simulations were designed to represent several scenarios: Rakai; a hypothetical Rakai-like population with no behavioral change; Rakai with STD intervention implemented in years 3, 10, or 20 of the epidemic; and a hypothetical Rakai-like population without behavioral change, with STD intervention in years 3, 10, or 20.
The model fit the Rakai HIV epidemic assuming a considerable behavioral risk reduction starting at the end of the Ugandan civil war in 1986. (The authors estimate that the epidemic began around 1978). STD prevalences fell after the assumed behavioral risk reduction starting in 1986. The simulated decline in syphilis prevalence approximated the decline observed in Rakai between 1992 and 1996. The model also fit time trends in gonorrhea and HIV prevalence, confirming the adequacy of the assumed behavioral risk reduction. HSV-2 showed a comparatively slow and small decline.
The simulations confirm that the proportion of new HIV infections preventable by STD treatment decreases during the evolution of generalized HIV epidemics. For populations with unchanged risk behaviors, the decline in impact is greatest during the first 10 years of the epidemic. The conclusion holds true for populations with varying patterns of sexual behavior and across a range of scenarios of HIV/STD transmission dynamics. The slight decline in STDs over time in simulations without behavior change indicates that HIV-attributable mortality contributes only modestly to the changing role of STDs. The dynamics of the spread of HSV-2 also contributed little to the decreasing impact of bacterial STD treatment on the incidence of HIV.
Behavioral change such as that in Uganda is a powerful determinant of the evolution of an HIV epidemic and the relative impact of subsequent STD treatment programs. The authors counsel caution in interpreting the outcome of this model, since the actual magnitude of the change in risk behavior in Uganda is not known, with data lacking up until the late 1980s. Data are subject to reporting biases, and it is not possible to determine the relative contributions of the end of the civil war and the simultaneous implementation of the national AIDS control program.
The data do shed light on the discrepancy between the Rakai and Mwanza trials. The Rakai trial began around the 17th year of the epidemic. Mwanza's trial, by contrast, started around the 10th year of the epidemic. Mwanza's population had apparently engaged in no behavioral change, while there had been significant risk reduction in Uganda.
The study concludes that the impact of STD treatment on HIV incidence decreases over time as a result of the natural dynamics of the HIV epidemic, the effect mainly being important within the first decade of the epidemic. A stronger contributor to a decreasing role of curable STDs in HIV transmission can be behavior change. The lack of impact of STD treatment in the Rakai trial may be due to the preceding behavioral change in Uganda after the civil war. Improved STD treatment may have more impact in earlier-stage HIV epidemics and in areas such as South Africa where behavior has not significantly changed.
(Commentary from the CDC HIV/STD/TB Prevention News Update 12/03/02)