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STD Control Research Strategy
Overview
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
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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. |
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Specific
intensive STD interventions such as selective mass (presumptive) STD
treatment to high-frequency transmitters can bring about rapid
reductions in STD prevalence. |
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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. |
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Treatment
of asymptomatic STDs is critical to reducing STD prevalence and the
often serious complications of STD. |
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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. |
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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 |
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Lack
of male circumcision is correlated with higher risks of HIV acquisition. |
Future Directions
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.
Guiding Principles:
- 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).
HPTN Studies
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HPTN 036 |
HIV Prevalence, Incidence, and HSV-2 Prevalence Among High-Risk MSM in Perú |
(Concluded) |
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HPTN 039 |
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 |
(Participants Off Study & Primary Analysis Complete) |
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HPTN 039-01 |
Ancillary Study: Prospective Cohort Study of HPTN 039 Seroconverters: The Effect of HSV-2 Suppression on HIV-1 Viral Set Point |
(Closed to Accrual) |
HPTN STD Control Scientific
Committee
Contacts
King Holmes, Chair
Scott Rose, CORE Contact
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