HIV treatment for prevention

Abstract

"No virus, no transmission." Studies have repeatedly shown that viral load (the quantity of virus present in blood and sexual secretions) is the strongest predictor of HIV transmission during unprotected sex or transmission from infected mother to child. Effective treatment lowers viral load to undetectable levels. If one could identify and treat all HIV-infected people immediately after infection, the HIV/AIDS epidemic would eventually disappear.Such a radical solution is currently unrealistic. In reality, not all people get tested, especially when they fear stigma and discrimination. Thus, not all HIV-infected individuals are known. Of those HIV-positive individuals for whom the diagnosis is known, not all of them have access to therapy, agree to be treated, or are taking therapy effectively. Some on effective treatment will stop, and in others, the development of resistance will lead to treatment failure. Furthermore, resources are limited: should we provide drugs to asymptomatic HIV-infected individuals without indication for treatment according to guidelines in order to prevent HIV transmission at the risk of diverting funding from sick patients in urgent need? In fact, the preventive potential of anti-HIV drugs is unknown. Modellers have tried to fill the gap, but models differ depending on assumptions that are strongly debated. Further, indications for antiretroviral treatments expand; in places like Vancouver and San Francisco, the majority of HIV-positive individuals are now under treatment, and the incidence of new HIV infections has recently fallen. However, correlation does not necessarily imply causation. Finally, studies in couples where one partner is HIV-infected also appear to show that treatment reduces the risk of transmission.More definite studies, where a number of communities are randomized to either receive the "test-and-treat" approach or continue as before, are now in evaluation by funding agencies. Repeated waves of testing would precisely measure the incidence of HIV infection. Such trials face formidable logistical, practical and ethical obstacles. However, without definitive data, the intuitive appeal of "test-and-treat" is unlikely to translate into action on a global scale. In the meantime, based on the available evidence, we must strive to provide treatment to all those in medical need under the current medical guidelines. This will lead to a decrease in HIV transmission while "test-and-treat" is fully explored in prospective clinical trials.

Figure 1

Viral load categories for participants of the SHCS in Switzerland. Adapted from Ledergerber et al, presented at CROI 2010 (with permission). Viral load categories: Stably suppressed: Three consecutive HIV-1 RNA values below detection limit (<50 copies/mL). Improving: A detectable followed by two undetectable values. Unstable: a) Detectable - undetectable - detectable; or b) Undetectable - detectable - undetectable. Failing: An undetectable followed by two detectable values. Stable failure: Three consecutive detectable viral load values

Figure 2

Number of patients active on HAART and newly discovered HIV in Bristish Columbia, Canada. Adapted from Montaner et al, Lancet 2010,376(9740):532-539 (with permission).

Figure 3

Attrition in a HAART initiation study. Study enrolment, HIV test results, CD4 cell count results and HAART initiation in two clinics of Durban, South Africa. Adapted from Bassett et al, AIDS 2010, 24(Suppl 1):S37-S44 (with permission).