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
Background
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.
Methods
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.
Findings
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.
Interpretation
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
Comment
HIV drugs for treatment, and for prevention
François Dabis, Marie-Louise Newell, Bernard Hirschel
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