Reassessing the hypothesis on STI control for HIV prevention
hypothesis on STI control for HIV prevention.
2008) Reassessing the hypothesis on STI control for HIV prevention.
While the often cited prevention success stories of Thailand and Uganda , are inspiring and informative, some of the specific socio-cultural, historical, and other factors in the southern African region—now the global epicenter of the HIV pandemic—are distinctive. In these “hyper-endemic” settings, where adult HIV prevalence ranges from 12% to 26% , HIV transmission is highly generalized, whereas Thailand's epidemic was much more concentrated. There, HIV transmission was driven mainly by brothel-based sex work—enabling the aggressive “100 percent condom” programs to be feasible, enforceable, and effective ,. The unprecedented HIV decline and associated behavior change in Uganda, mainly involving large reductions in multiple sexual partnerships ,–, occurred some 20 years ago and under rather different contextual and programmatic circumstances.
More recently, male circumcision has been studied as a possible means for preventing HIV transmission. Circumcision essentially erects a permanent barrier against HIV through removal of the foreskin. The mucosal foreskin glans of the penis is rich in cells receptive to HIV infection . Powerful observational data suggested that circumcised men were much less likely to acquire HIV, implying the glans is the main site of HIV acquisition in men. Three randomized controlled trials demonstrated a minimum of 60% reduction in HIV acquisition [-]. Consequently, circumcision has been sought for high-risk subjects, but the logistical challenges of providing enough procedures to make an immediate impact are daunting. Many infants born in resource-constrained countries lack access to safe circumcisions, and there has been a distinct lack of political will or patience to institute safe neonatal circumcision worldwide.
Reassessing the hypothesis on STI control for ..
Effective (and cost-effective) strategies to control the HIV epidemic are likely to be those that address as many of the individual drivers of local epidemics as possible. A wide range of questions must be addressed to investigate both the levels of efficacy associated with prevention efforts under various epidemic conditions and their cost. What is the individual effect of test-and-treat strategies on the incidence of HIV infection in the presence of other ongoing prevention efforts? What is the combined effect of test-and-treat and other modalities? What are the synergies and potential negative interactions among modalities? What are the characteristics of the communities that would permit cost-effective deployment of a package of interventions, and how can we assess these characteristics? How do we tailor the package to local epidemic conditions?
To assess population benefit resulting from an intervention, it is useful to find metrics that characterize epidemics in these populations. One proposed metric arising from a focus on communities rather than individuals is community-level viral load, which is often mentioned in the context of test-and-treat strategies, to reflect the notion that mean viral load describes potential for HIV infection to spread within a community. A study detected an association between mean viral load and incidence of HIV infection in a cohort of injection drug users . This association became nonsignificant after ART became more widely available in the population, reducing mean viral load to ]. Although intuitive and useful in some contexts, the reduction of the characteristics of an epidemic to a single metric may not be adequate for investigating ART as a way to control the epidemic. In fact, the impact of the amount of circulating virus depends on its distribution among infected persons and on their sex networks, neither of which is reflected in a population mean. HIV infection does not spread evenly throughout a community; it spreads through sex networks with varying transmission rates that depend on factors that may vary greatly across communities. Therefore, although incidence may well correlate with a population mean viral load, it would probably also correlate with other epidemic features, such as prevalence of recent HIV infection, frequency of risky behavior, and nature of social and sex networks (eg, concurrency and rates of partner change). To be useful for developing prevention policy, all of these factors must be reflected in the metrics used. Oversimplification may lead to implementation of interventions that are inadequate to impact local epidemics favorably and may not be cost-effective. We believe that research should now be directed to establish ways to characterize epidemics in different settings for purposes of providing information required for developing and implementing cost-effective prevention strategies with the goal of controlling local epidemics.
Reassessing the hypothesis on STI control for HIV prevention.
The development of HIV-prevention interventions is a complex process. In general, observational studies, pretrial screening, in vitro and animal studies are the hypothesis generating investigations, which provide the rationale for hypothesis testing trials. Randomized trials provide evidence of efficacy and there have been over 30 HIV-prevention trials of which only four reported reduction in HIV acquisition . Here, we review examples of sexually transmitted disease (STD) control, microbicide, male circumcision and vaccine HIV-prevention trials.
There was, compelling evidence that STIs are associated with HIV acquisition and transmission, and this provided the rationale for trials of STI control to prevent HIV infection.
[46 x Reassessing the hypothesis on STI control for HIV prevention…
the hypothesis on STI control for HIV prevention.
Wawer MJ: Reassessing the hypothesis on STI control for HIV prevention
Reassessing the hypothesis on STI control for HIV prevention ..
Reassessing the hypothesis on STI control for HIV prevention Lancet 2008;371:2064-5.[Medline]
Gray RH , Wawer MJ : Reassessing the hypothesis on STI control for ..
“Reassessing the hypothesis on STI control for ..
Reassessing the hypothesis on STI control for Prevention
A recent trial of a vaccine (Merck V520) that stimulated HIV responsive T cells failed to prevent HIV acquisition . However, the vaccine also failed to reduce viral load at set point. Furthermore, more infections were observed in the group that received the vaccine than in the control group, but the reason for this phenomenon is not known . Another ongoing trial that tests HIV proteins delivered in a canary pox virus vector and boosted with gp120 will be completed in 2009.
Volume 87, Number 11, November 2009, 805-884
Before the STI-HIV trials were launched, STI treatment was known to be efficacious (for STIs), with minimal side effects. The results of the Mwanza trial confirmed the already widely held belief that STI control almost surely slowed the spread of HIV. Recent meta-analyses of observational studies provide further corroboration [,,]. The nine post-Mwanza trials do not confirm that hypothesis, but neither do they offer any basis for rejecting it, given the nature of statistical testing and, more importantly, given their multiple design flaws enumerated here. RCTs impose an unachievable standard of proof on the possible contribution of STIs to the spread of HIV.
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We have presented the reductions in HIV incidence and prevalence that could be achieved through the introduction of a hypothetical HSV2 vaccination in certain scenarios. Should a vaccine become available, the real-world impact of scaled-up HSV2 interventions would be tempered by logistical constraints, but HSV2 vaccination has considerable potential as an HIV preventive intervention. Intensified efforts are needed to develop an effective vaccine against HSV2.
Control of sexually transmitted infections for HIV prevention
There are four opportunities for HIV prevention: before exposure, at the moment of exposure, immediately after exposure, and as secondary prevention focused on infected subjects. Until recently, most resources have been directed toward behavioral strategies aimed at preventing exposure entirely. Recognizing that these strategies are not enough to contain the epidemic, investigators are turning their attention to post-exposure prevention opportunities. There is increasing focus on the use of ART–either systemic or topical (microbicides)–to prevent infection at the moment of exposure. Likewise, there is growing evidence that ART treatment of infected people could serve as prevention as well. A number of ongoing clinical trials will shed some light on the potential of these approaches. Above all, prevention of HIV requires decision-makers to focus resources on strategies that are most effective. Finally, treatment of HIV and prevention of HIV must be considered and deployed together.
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