Prevention of HIV-1 infection with early antiretroviral therapy.

TitlePrevention of HIV-1 infection with early antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2011
AuthorsCohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JHS, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR
Corporate AuthorsHPTN 052 Study Team
JournalN Engl J Med
Volume365
Issue6
Pagination493-505
Date Published2011 Aug 11
ISSN1533-4406
KeywordsAdolescent, Adult, Anti-Retroviral Agents, Disease Progression, Disease Transmission, Infectious, Drug Therapy, Combination, Female, HIV Infections, HIV Seropositivity, HIV-1, Humans, Kaplan-Meier Estimate, Male, Proportional Hazards Models, Sexual Partners, Spouses, Treatment Outcome, Young Adult
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.).

DOI10.1056/NEJMoa1105243
Alternate JournalN. Engl. J. Med.
PubMed ID21767103
PubMed Central IDPMC3200068
Grant ListK24 AI051982 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
R24 HD042854 / HD / NICHD NIH HHS / United States
U01 AI068617 / AI / NIAID NIH HHS / United States
U01 AI068617-05 / AI / NIAID NIH HHS / United States
U01 AI068619 / AI / NIAID NIH HHS / United States
U01 AI068619-05 / AI / NIAID NIH HHS / United States
U01-AI068613 / AI / NIAID NIH HHS / United States
U01-AI068617 / AI / NIAID NIH HHS / United States
U01-AI068619 / AI / NIAID NIH HHS / United States
UM1 AI068617 / AI / NIAID NIH HHS / United States
UM1 AI068617-07 / AI / NIAID NIH HHS / United States
UM1 AI068619 / AI / NIAID NIH HHS / United States
UM1 AI068619-07 / AI / NIAID NIH HHS / United States
UM1-AI068613 / AI / NIAID NIH HHS / United States
UM1-AI068617 / AI / NIAID NIH HHS / United States
UM1-AI068619 / AI / NIAID NIH HHS / United States