A recent posting linked to the abstract of a study evaluating the impact of ART on HIV transmission that was presented at CROI earlier this year. The full results have now been published in the Lancet. The paper is generating considerable press coverage because the effect of ART was dramatic, equating to a 92% reduction in risk of transmission. The study involved 3,381 couples in which one partner was HIV positive and the other negative. Out of 103 cases of transmission that were documented, 102 occurred in couples where the positive partner was not using ART. In the remaining case, ART had only very recently been initiated. Although the results represent the most compelling evidence to date that ART can reduce the risk of sexual transmission of HIV infection, it’s worth noting that the main purpose of the trial was to investigate the impact of suppressing herpes simplex virus infection with acyclovir on HIV transmission (these primary results have already been published). The analysis of the effect of ART was thus “post hoc” meaning it was not pre-specified in the protocol (there is an ongoing trial called HPTN 052 in which the primary endpoint is the impact of ART on transmission but results are not anticipated until 2014).
In an accompanying commentary in the Lancet, several scientists argue that these results call for rapid development of trials of a “test and treat” approach to reducing HIV incidence in which the main goal will be preventing transmission. However the paper also makes it clear that transmission risk is highest among people who need ART for their individual health; given the stalling in funding to support treatment access globally, arguably the most important implication of the study is that this shortfall needs to urgently be addressed for reasons of public health, as well as to ensure the wellbeing of people with HIV who are currently being turned away from treatment programs due to lack of resources.
The Lancet, Early Online Publication, 27 May 2010doi:10.1016/S0140-6736(10)60705-2
Dr Deborah Donnell PhD, Jared M Baeten MD, James Kiarie MBChB, Katherine K Thomas MS, Wendy Stevens MBBCh, Craig R Cohen MD, James McIntyre MBBCh, Jairam R Lingappa MD, Connie Celum MD, for the Partners in Prevention HSV/HIV Transmission Study Team
High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners.
Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per μL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants.
3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161—265) cells per μL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0·37 (95% CI 0·09—2·04) per 100 person-years in those who had initiated treatment and 2·24 (1·84—2·72) per 100 person-years in those who had not—a 92% reduction (adjusted incidence rate ratio 0·08, 95% CI 0·00—0·57, p=0·004). In participants not on ART, the highest HIV-1 transmission rate (8·79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per μL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per μL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL.
Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission.
The Lancet, Early Online Publication, 27 May 2010doi:10.1016/S0140-6736(10)60838-0
François Dabis, Marie-Louise Newell, Bernard Hirschel