Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

TitleAntiretroviral Therapy for the Prevention of HIV-1 Transmission.
Publication TypeJournal Article
Year of Publication2016
AuthorsCohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JHS, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR
Corporate AuthorsHPTN 052 Study Team
JournalN Engl J Med
Volume375
Issue9
Pagination830-9
Date Published2016 09 01
ISSN1533-4406
KeywordsAdult, Anti-Retroviral Agents, Disease Transmission, Infectious, Female, Follow-Up Studies, HIV Infections, HIV Seropositivity, HIV-1, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Risk, Sexual Partners, Young Adult
Abstract

BACKGROUND: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

METHODS: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.

RESULTS: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.

CONCLUSIONS: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).

DOI10.1056/NEJMoa1600693
Alternate JournalN. Engl. J. Med.
PubMed ID27424812
PubMed Central IDPMC5049503
Grant ListU01-AI068617 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
U01-AI068613 / AI / NIAID NIH HHS / United States
U01 AI068619 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069456 / AI / NIAID NIH HHS / United States
UM1-AI068619 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
U01-AI068619 / AI / NIAID NIH HHS / United States
UM1 AI069518 / AI / NIAID NIH HHS / United States
UM1 AI069399 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
U01 AI068617 / AI / NIAID NIH HHS / United States
U01 AI068613 / AI / NIAID NIH HHS / United States
UM1 AI068619 / AI / NIAID NIH HHS / United States
UM1 AI068613 / AI / NIAID NIH HHS / United States
UM1-AI068613 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
UM1-AI068617 / AI / NIAID NIH HHS / United States
UM1 AI068617 / AI / NIAID NIH HHS / United States