Antiretroviral therapy dramatically reduces transmission of HIV to sexual partners

Antiretroviral therapy for the prevention of HIV-1 transmission.

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, 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. N Engl J Med. 2016 Jul 18. [Epub ahead of print]

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.).

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Editor’s notes: The HPTN 052 trial has been a landmark study in establishing antiretroviral therapy as a strategy for preventing onward transmission of HIV. It was a study of more than 800 couples. More than half of the couples were in African countries. In each couple, one sexual partner was HIV positive and the other HIV negative.  The participants living with HIV were randomised either to receive immediate antiretroviral therapy or to delay until their CD4 count fell to 350, an approved approach at that time. The HIV negative partners were then monitored for acquisition of HIV.  When new HIV infections occurred, the virus was studied for genetic similarity to the virus of the known positive partner. The interim analysis was published in 2011.  It illustrated the programme to be so effective that the randomisation was ended and all the participants living with HIV were offered antiretroviral therapy. 

This article presents data after five years of follow-up, and if anything the results are even more remarkable. In more than 10 000 person-years of follow up, there were only eight transmissions of genetically linked virus from participants receiving antiretroviral therapy. Of these transmissions, four occurred early in treatment when the viral load would not be expected to be suppressed.  The other four occurred after treatment failure. In this enormous study, there were therefore no linked transmissions from participants who were stable on treatment without detectable viraemia. The study provides powerful support for the UNAIDS 90-90-90 treatment target.  The widest possible effective use of antiretroviral therapy will not only improve the health of people treated but could have a dramatic effect on new HIV infections.

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