Final results of HPTN 052, the watershed randomized trial that positioned antiretroviral therapy (ART) as an HIV prevention strategy, indicate that participants starting ART at a high CD4 count sustained a 93% lower risk of transmitting HIV to sex partners through more than five years of follow-up. The early-ART group enjoyed that benefit even though the deferred-ART group could begin treatment at the 1.7-year interim analysis. The HPTN 052 team concluded "successful treatment of HIV-1 is a highly effective tool for the prevention of sexual transmission of the virus." The results were presented at AIDS 2016.
HPTN 052 enrolled 1763 couples with one HIV-positive partner and one HIV-negative partner at 13 sites in nine countries. Positive partners, all with a CD4 count of 350 to 550 cells/mm3, were randomized to start ART immediately (early-ART group) or to delay ART until their CD4 count fell below 250 cells/mm3 or an AIDS illness developed (delayed-ART group). An interim analysis after a median follow-up of 1.7 years determined that HIV-positive early-ART participants had a 96% lower risk of transmitting HIV to their steady partner. At that point, in May 2011, HIV-positive partners in the delayed-ART group were offered ART regardless of CD4 count and the study continued through May 2015.
The trial randomized 886 couples to the early-ART group and 877 to the delayed-ART group. At the May 2011 interim analysis, 97% of initially HIV-positive partners remained in the study, as did 89% of their HIV-negative partners. One year after the report of interim results, 83% of initially positive partners in the delayed-ART group who stayed in the study had started ART. After 5.5 years of follow-up in May 2015, 87% of initially positive partners and 66% of couples remained in the study. At that point, 96% of HIV-positive partners who remained in follow-up in the delayed-ART group had started ART.
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Throughout the entire study, 78 initially HIV-negative partners became infected for an overall incidence of 0.9%. Fifty-nine partners in the delayed-ART group and 19 in the early-ART group became infected. Of the 78 new HIV infections, the researchers could genetically analyze 72 viral samples to determine whether the initially positive partner -- or someone outside the couple -- had infected the negative partner. Genetic analysis determined that 26 of these 72 new infections (36%) probably resulted from sex outside the couple. Of the remaining 46 linked infections, three occurred in the early-ART group and 43 in the delayed-ART group.
Eight linked infections occurred after the initially positive partner started ART. Four of these eight infections were diagnosed fewer than 90 days after the positive partner began ART, and further analysis suggested the positive partner had not attained viral suppression when the partner became infected. The other four new HIV infections occurred after ART had failed in the initially positive partner.
Intention-to-treat analyses based on the initially positive partner's randomization determined that early ART was associated with a 97% lower risk of linked transmission than delayed ART at the May 2011 interim analysis (hazard ratio [HR] 0.03, 95% confidence interval [CI] 0.00 to 0.20). At the final analysis in May 2015, early ART was associated with a 93% lower risk of linked HIV transmission during the entire study (HR 0.07, 95% CI 0.02 to 0.22). In the delayed-ART group, HIV incidence fell steeply from 2.08 per 100 person-years through interim follow-up in May 2011 to 0.29 per 100 person-years after that point, when all initially positive partners became eligible for ART.
Multivariate intention-to-treat analysis determined that every 10-fold higher baseline viral load in the initially positive partner almost doubled the risk of a genetically linked partner infection (HR 1.88, 95% CI 1.24 to 2.87). Condom use also had an independent impact on linked partner infection: Baseline condom use of 100% cut chances of a linked partner infection 66% compared with less than 100% condom use (HR 0.34, 95% CI 0.15 to 0.75).
The link between higher viral load and HIV transmission, the HPTN 052 team noted, emphasizes the importance of counseling about "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."