The HPTN 052 trial enrolled 1763 serodiscordant couples at 13 sites in nine countries. The majority of couples (97%) were heterosexual, and 94% were married. Index participants (i.e., those with HIV-1 infection) had CD4+ counts of 350 to 550 cells per cubic millimeter. Couples were randomly assigned to two study groups. In the early-ART group, index participants initiated ART at the time of enrollment. In the delayed-ART group, index participants initiated ART when two consecutive CD4+ counts fell below 250 cells per cubic millimeter or they had an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness).
In an interim analysis of study data that was performed in May 2011 after a median follow-up of 1.7 years, investigators found that early ART was associated with a 96% lower risk of index-to-partner, genetically linked HIV-1 infections than was delayed ART. The interim analysis also showed that early ART provided health benefits to the index participants. The data and safety monitoring board requested immediate release of those results. Accordingly, after May 2011, all index participants who were not already receiving ART were offered ART, regardless of the CD4+ count. The trial continued as prespecified through May 2015 to assess the durability of the effect of ART on HIV-1 transmission. This report presents the final results of the HPTN 052 trial.
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.
The median follow-up time was 5.5 years (range, 0.0 to 9.9) for the early-ART group and 5.5 years (range, 0.1 to 9.9) for the delayed-ART group. 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.
Of the 46 linked partner infections, 3 in the early-ART group and 5 in the delayed-ART group were diagnosed after the infected participant initiated ART : in 4/8 cases, the partner was diagnosed with HIV-1 infection less than 90 days after the index participant started ART, further analysis suggesting that all four of these infections probably occurred before the infection was virally suppressed in the index participant. In the other four cases, partner infection occurred after ART failed in the index participant. Less frequent condom use (<100%, by self-report by either partner) was associated with an increased risk of both linked infections and all infections among partners. In summary, In all eight cases, the index participant was most likely viremic at the time of HIV-1 transmission, although it was not possible to measure the viral load at the time of the transmission event. The relationship between viremia and HIV transmission emphasizes the importance of counseling with respect to the potential for HIV-1 transmission before viral suppression is achieved, of close monitoring of the viral load during treatment, and of responding quickly in cases of ART failure
The early initiation of ART led to a sustained decrease in genetically linked HIV-1
infections in sexual partners. The final results of the HPTN 052 study show that successful treatment of HIV-1 is a highly effective tool for the prevention of sexual transmission of the virus.