Antiretroviral Therapy for the Prevention of HIV-1 Transmission
N Engl J of Medicine July 18, 2016
Myron S. Cohen, M.D., Ying Q. Chen, Ph.D., Marybeth McCauley, M.P.H., Theresa Gamble, Ph.D., Mina C. Hosseinipour, M.D., Nagalingeswaran Kumarasamy, M.B., B.S., James G. Hakim, M.D., Johnstone Kumwenda, F.R.C.P., Beatriz Grinsztejn, M.D., Jose H.S. Pilotto, M.D., Sheela V. Godbole, M.D., Suwat Chariyalertsak, M.D., Breno R. Santos, M.D., Kenneth H. Mayer, M.D., Irving F. Hoffman, P.A., Susan H. Eshleman, M.D., Ph.D., Estelle Piwowar-Manning, M.T., Leslie Cottle, B.S., Xinyi C. Zhang, Ph.D., Joseph Makhema, M.B., B.Ch., Lisa A. Mills, M.D., Ravindre Panchia, M.B., B.Ch., Sharlaa Faesen, M.B., B.Ch., Joseph Eron, M.D., Joel Gallant, M.D., Diane Havlir, M.D., Susan Swindells, M.B., B.S., Vanessa Elharrar, M.D., David Burns, M.D., Taha E. Taha, M.B., B.S., Karin Nielsen-Saines, M.D., David D. Celentano, Sc.D., Max Essex, D.V.M., Sarah E. Hudelson, B.S., Andrew D. Redd, Ph.D., and Thomas R. Fleming, Ph.D., for the HPTN 052 Study Team*
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.
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.
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.
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.)
Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society