Prevention of HIV-1 infection with early antiretroviral therapy - PubMed (original) (raw)

Randomized Controlled Trial

. 2011 Aug 11;365(6):493-505.

doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18.

Ying Q Chen, Marybeth McCauley, Theresa Gamble, Mina C Hosseinipour, Nagalingeswaran Kumarasamy, James G Hakim, Johnstone Kumwenda, Beatriz Grinsztejn, Jose H S Pilotto, Sheela V Godbole, Sanjay Mehendale, Suwat Chariyalertsak, Breno R Santos, Kenneth H Mayer, Irving F Hoffman, Susan H Eshleman, Estelle Piwowar-Manning, Lei Wang, Joseph Makhema, Lisa A Mills, Guy de Bruyn, Ian Sanne, Joseph Eron, Joel Gallant, Diane Havlir, Susan Swindells, Heather Ribaudo, Vanessa Elharrar, David Burns, Taha E Taha, Karin Nielsen-Saines, David Celentano, Max Essex, Thomas R Fleming; HPTN 052 Study Team

Collaborators, Affiliations

Randomized Controlled Trial

Prevention of HIV-1 infection with early antiretroviral therapy

Myron S Cohen et al. N Engl J Med. 2011.

Abstract

Background: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.

Methods: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.

Results: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01).

Conclusions: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

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Conflict of interest statement

No other potential conflict of interest relevant to this article was reported.

Figures

Figure 1

Figure 1. Enrollment and Outcomes

This trial profile describes recruitment of couples from the general population, randomization, HIV-1–uninfected partner's enrollment, seroconversion at baseline, retention, and loss-to-follow-up for assessment of the primary end point of linked HIV-1 transmission. Enrolled partners were followed on a quarterly-visit schedule, although attendance at semiannual visits is shown.

Figure 2

Figure 2. Kaplan–Meier Estimates for Partner-Linked and Any HIV-1 Transmission and for Clinical and Composite Monitoring Events

Shown are Kaplan–Meier estimates for the cumulative probabilities of linked HIV-1 transmission between partners (Panel A), any HIV transmission (Panel B), clinical events (Panel C), and composite monitoring events (Panel D) among participants in the early-therapy and delayed-therapy groups.

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