ArticlesEffects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial
Introduction
Combination antiretroviral treatment has reduced morbidity and mortality associated with HIV-1 infection over the past two decades.1, 2 However, the best timing of treatment initiation in people with high CD4 cell counts remains unknown. Findings of observational studies of treatment for HIV-1 infection lend support to early initiation of antiretroviral treatment,3, 4, 5, 6 but data from randomised studies are scarce. In a randomised trial from Haiti,7 HIV-1 disease progression was delayed and survival extended when antiretroviral treatment was started at CD4 counts of 200–350 cells per μL, compared with initiation at CD4 counts of less than 200 cells per μL.
The HIV Prevention Trials Network (HPTN) 052 study is a worldwide, multicentre, randomised controlled trial designed to compare early versus delayed antiretroviral treatment for HIV-1-infected adults with CD4 counts of 350–550 cells per μL. Interim results after 1·7 years of follow-up showed a 96% reduction in HIV-1 transmission to a sexual partner and delayed time to AIDS events with early treatment.8 Here, we present a planned analysis of HPTN 052, focusing on clinical outcomes that reflect overall recorded morbidity and mortality related to HIV-1 infection. These outcomes might be a result of HIV-1 disease progression, the effect of HIV-1 infection on serious non-AIDS clinical events, adverse events resulting from treatment, or a combination of these.
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Study population
We enrolled HIV-1-serodiscordant couples (one with HIV-1 infection and the other without) from nine countries: Botswana (one site), Brazil (two sites), India (two sites), Kenya (one site), Malawi (two sites), South Africa (two sites), Thailand (one site), the USA (one site), and Zimbabwe (one site).8 Since the US site enrolled only two couples during the pilot phase of the study and did not participate in the full study, the two HIV-1-infected participants enrolled at that site were excluded
Results
1763 HIV-1-infected individuals with a serodiscordant partner were enrolled in the trial and underwent randomisation; 886 were assigned to the early treatment group and 877 were allocated to delayed antiretroviral treatment (figure 1). Two patients from the USA were excluded from the delayed treatment group after randomisation. Table 1 presents baseline characteristics. Median age of participants was 33 years (IQR 27–39), and half the study population were men. The median baseline CD4 count was
Discussion
Our findings from the HPTN 052 study cohort show the broader clinical effect of early initiation of antiretroviral treatment, including effects in relation to serious non-AIDS medical disorders and HIV-1-associated events. Time to first serious clinical event was longer in patients assigned early antiretroviral treatment, despite the fact that serious non-AIDS events were uncommon. However, a substantial number of AIDS-related and HIV-1-related events were recorded among study participants
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See appendix (pp 146–50) for a full list of Study Team members