Some conclusions

The results from the herpes and STI trials are (so far) disappointing and herpes infection alone continues to be implicated in a large proportion of HIV infection.

The herpes trials appear to have encountered a problem that has severely impaired the first generation of microbicide trials- that of adherence, and of developing better measures of adherence than unreliable self-report without violating trial participants’ rights or safety.

Suppressing STIs to suppress HIV may continue to make a good deal of epidemiological sense, but it may take a totally suppressive therapy like an HSV-2 vaccine, or using symptomatic STI management alongside other measures such as circumcision or a microbicide, for it to make a great deal of difference to HIV transmission.

In an article in the journal AIDS in 2010,¹ several of the researchers involved in the trials described in this chapter said that the reduced emphasis on STI control in HIV-control programmes following the negative trial results was a tactical mistake. Despite these results, the evidence for a link between STI and HIV infection remained ‘compelling’ and STI treatment as HIV prevention was still a promising avenue of research to pursue.

The RCTs of bacterial STIs were largely conducted in populations with mature epidemics and relatively low levels of STIs. In addition, the control arms employed STI treatment and HIV-prevention services beyond the local standard of care. There is, therefore, considerable room for better-designed RCTs of bacterial STI treatment. Treatment of bacterial vaginosis and candida (which may also be implicated in HIV infection) could be incorporated in these.

The RCTs of herpes suppression, on the other hand, convincingly demonstrated that the intervention chosen was not sufficiently powerful to make a difference to the effect of HSV-2 infection on susceptibility to, or infectiousness with, HIV. Since these trials were first developed, researchers have discovered a great deal about how asymptomatic HSV-2 infection may facilitate HIV transmission.

The writers suggested trials of stronger anti-herpes drugs and research into the development of an HSV-2 vaccine.

They also recommend a trial of HPV vaccination as a possible HIV transmission intervention, given the results demonstrated by Bertrand Auvert at Orange Farm.

They conclude: “The evidence suggests that the basic concept [of STI treatment to prevent HIV] is sound and it is time to begin a new phase of exploration of how, when and in whom to include STI control as a key component of HIV prevention. This new phase should be driven by basic research on the biological mechanisms underpinning STI–HIV interactions.”