Twenty-five years after the discovery of the HIV virus, prevention is at an impasse. A vaccine remains elusive. Vaginal microbicides have so far failed to show significant long-term benefit. Treatment of sexually transmitted infections, including herpes simplex has no measurable effect on HIV transmission. Male circumcision halves the risk of HIV transmission from females to males but is not (yet) a widely used public health measure, although the South African government is preparing an implementation plan. As a consequence, effective prevention has continued to rely on behavioural change and condom use, but these methods have their limits. At their current or anticipated level of use these methods are not effective enough to contain the pandemic in countries with high incidence and prevalence of HIV infection.
Viral load in the index HIV-infected individual is the most important determinant of transmission in heterosexual couples and from mother-to-child. Antiretroviral therapy (ART) lowers viral load in all body compartments and decreases to a very low rate the risk of transmission. It is thus legitimate to raise the following question: Is ART more efficacious than any of the previously described prevention strategies? Head-to-head comparisons are not available and are unlikely to be promoted, but in studies where the systematic use of condoms was encouraged in sero-discordant couples, results were very different depending whether index patients were on ART (0.5% of HIV acquisition per person per year [ppy]) or not (12% ppy).
However, what is lacking is a randomised trial together with sound implementation research evaluating whether ART delivered at an earlier than usual stage of the infection can be made to work in preventing onward transmission of HIV. The Treatment as Prevention (TasP) trial aims to address this very important question and produce such evidence, from a rural area in KwaZulu-Natal, the province with the highest HIV incidence and antenatal prevalence in South Africa, the country with one of the highest HIV burden in sub-Saharan Africa, the continent where 90% of new HIV infections occur.
Principal Research Question
Will HAART given to people diagnosed to be HIV infected but who are not yet eligible for treatment reduce the incidence of new HIV infections? This question will be addressed in a cluster randomised trial, with a full prevention and testing strategy being provided in both the intervention and the control arms. The trial is anticipated to take place in the Hlabisa sub-district outside of the DSA (to avoid over-researching the DSA) and is likely to be phased in over 18 months, with a full coverage thereafter.
Secondary research questions
Secondary endpoints will be divided into those applicable at an individual level: TB, AIDS and non-AIDS related morbidity, safety, and those with public health relevance: including acceptability, the challenges for the health care system and health care professionals.
An application for funding is being developed for submission in March 2010 to the ANRS, with a possible start date late 2010 or early 2011. During 2010, the Social Science research team will work with the community in preparation for the trial.