Antiretroviral Therapy for the Prevention of HIV-1 Transmission

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 .).

Figure 1. Study Randomization and Outcomes

Shown are data on the randomization of couples, enrollment of partners, partner visit attendance, and reasons for early discontinuation of partners in the study. Thirty additional partners (17 in the early-ART group and 13 in the delayed-ART group) were enrolled throughout the course of the study to replace partners who discontinued their participation in the study before reaching a primary study end point. The four partners who were found to have HIV-1 infection at study enrollment were excluded from the analysis. Visit attendance is shown for annual visits only; actual study visits occurred at least quarterly. The data for annual visit attendance are presented as the number of partners (nonindex participants) who were retained per the number who were expected at each year-end visit. The number retained refers to the number of partners who completed visits or reached a study end point (i.e., death of the index participant or the diagnosis of HIV-1 infection in the partner). The expected number refers to the number of partners who did not discontinue participation in the study because of death or the termination of the relationship with the index participant before the end of the allowable visit period.

Figure 2. Kaplan–Meier Estimates of the Risk of HIV-1 Infection among Partners of Index Participants

Shown are the cumulative probabilities of all partner infections (Panel A) and genetically linked partner infections (Panel B) during study follow-up. The insets show the same data on an expanded y axis.