STD Control Research Strategy
Multiple studies have suggested that STDs are important cofactors in the transmission and acquisition of HIV infection. An "epidemiologic synergy" exists between STDs and HIV, and thus control of one may have beneficial effects on the control of the other. The primary hypothesis of the STD Control Scientific Committee is that interventions designed for more effective control of STDs should reduce the incidence of HIV. Results from two community randomized trials which address this hypothesis have been published. The results were contradictory - one study having positive results in decreasing HIV incidence (Mwanza), and the other study having limited or no effect on HIV incidence (Rakai). Data from a third trial (Musaka) were presented at the XIV International AIDS Conference in Barcelona; like Rakai, it found no impact. Careful analysis of the data from all three trials showed a unifying theme, namely that these studies need to be done in settings with high STD incidence and increasing HIV incidence.
Effective STD control requires both targeted and more generalized strategies. Targeted interventions that reduce transmission in core groups (such as sex workers) with a high rate of partner exchange, and bridging groups (such as migrant workers, truck drivers etc), who seed new sexual networks, have led to rapid STD control in several areas (e.g., Thailand; South African mining areas; and Nairobi, Kenya). Research has shown that improved access to quality STD services for the general population alone can have a measurable impact on HIV transmission, especially in populations with growing HIV epidemics. Although the highest research priority identified within the STD Scientific Committee at its first meeting was a community randomized hybrid study combining these interventions, the HPTN has not had either site capability or funding to approve such a trial. Meanwhile, the emergence of genital herpes, especially in the context of mature HIV epidemics, highlights the evolving nature of STD epidemiology. Recent data from Rakai show a nearly five-fold association of HSV-2 with HIV-1 acquisition. Building on the extensive literature that has shown that genital ulcers are a risk factor for HIV acquisition, the HPTN is supporting HPTN 039, which examines the effect of acyclovir mediated suppression of HSV-2 infection on the acquisition of HIV. Because antiretrovirals are still out of reach of the majority of those infected with HIV, and HIV-related immunosuppression facilitates HSV-2 clinical expression, HSV-2 infection is likely to become an important cofactor in mature epidemics, and thus increase the risk of HSV transmission.
What is known
- Targeted interventions that improve STD treatment and increase condom use in high-risk core/bridging networks may have the greatest impact on sexual transmission of curable STDs, HSV and HIV.
- Specific intensive STD interventions such as selective mass (presumptive) STD treatment to high-frequency transmitters can bring about rapid reductions in STD prevalence.
- Continuous access to improved STD services may have greater impact on HIV transmission than intermittent mass treatment in the general population and such services are important long-term elements of sustainable STD control.
- Treatment of asymptomatic STDs is critical to reducing STD prevalence and the often serious complications of STD.
- STD treatment is especially critical in populations with substantial rates of STDs and early or growing HIV epidemics. In later stages of the HIV epidemic, the contribution of STDs to the spread of HIV may be minimal.
- Genital ulcers are potent cofactors in both HIV transmission and acquisition, as evidenced by odds and risk ratios that are consistently higher than those for non-ulcerative STD. In addition to the curable causes of ulcers (chancroid and syphilis), HSV-2 is becoming a more important cause of ulcers in areas with mature HIV epidemics
- Lack of male circumcision is correlated with higher risks of HIV acquisition.
The STD Scientific Committee has focused its efforts on the successful implementation of HPTN 039 (suppressive HSV-2 therapy trial) in the field. The STD Scientific Committee continues to monitor the STD-HIV field of research for development of future study concepts. The STD Scientific Committee also plans to continue to increase the level of interaction with other working groups that are developing STD intervention studies, such as the microbicides and behavioral working groups.
- Any STD intervention trial designed to prevent HIV transmission/acquisition needs to be conducted in early phase epidemics with high incidence of HIV and STDs.
- STDs can serve as biomarkers or surrogate markers for HIV incidence.
- Trials must be designed in the context of the current state of HIV therapy in the community (may need to shift focus to transmission of HIV and transmission and/or STD acquisition).
HIV Prevalence, Incidence, and HSV-2 Prevalence Among High-Risk MSM in Perú
A Phase III, randomized, double-blind, placebo-controlled trial of acyclovir for the reduction of HIV acquisition among high risk HSV-2 seropositive, HIV-seronegative individuals
Ancillary Study: Prospective Cohort Study of HPTN 039 Seroconverters: The Effect of HSV-2 Suppression on HIV-1 Viral Set Point
HPTN STD Control Scientific Committee Contacts
King Holmes, Chair
Scott Rose, CORE Contact