Suppression of HIV prevents transmission

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Credit: Pic courtesy of a&u

Complete suppression of HIV replication appears 100% effective in preventing transmission of the virus, concludes a landmark trial on serodiscordant heterosexual couples, reports The New England Journal of Medicine.

The landmark HPTN 052 trial assessed the risk of HIV transmission in 1,763 heterosexual couples, in which one partner was HIV-positive and the other was not, according to Dr Myron Cohen, of the University of North Carolina Chapel Hill in a MedPage Today report.

Over the 5-year life of the trial, 46 people acquired the virus from their infected partners Cohen is quoted as saying at the 21st International AIDS Conference. But, dramatically, not one of the cases occurred when the infected partner’s virus was suppressed, Cohen said. “Does this work over a long period of time for people who are anxious to be suppressed? The answer is absolutely yes,” Cohen said. “We now have 10,000 person years (of follow-up),” Cohen said, with “zero transmissions from people who are suppressed.”

According to the report, Cohen and colleagues said the trial was designed to look at the long-term effect of HIV treatment on transmission, so the enrolled couples were randomly assigned to one of two groups. In one, the HIV-positive partner – the “index participant” – was treated immediately, while in the other the index partner waited for treatment until there was evidence of increasing immune system damage or an illness suggestive of Aids.

In initial results, reported in 2011, immediate therapy was associated with a 96% decrease in the risk of HIV transmission, even though all the couples were counselled about safe sex and given condoms. The trial was unblinded at that point, Cohen said, and people in the delayed treatment arm were offered antiretroviral therapy.

In an intention-to-treat analysis, comparing genetically linked infections in the two groups, early treatment was associated with a 93% lower risk of transmission during the entire study – down slightly from the risk reduction reported in 2011, Cohen and colleagues reported.

The initial benefit was not a big surprise to clinicians treating people with HIV, commented Dr Steven Deeks, of the University of California San Francisco. “When the virus meets antiviral drugs, good things happen,” he is quoted in the report as saying. And it’s “very, very striking” that after thousands of person-years of follow-up, the benefit persists and there were no cases of transmission when the virus was stably suppressed in the index participant, Deeks said.

Overall, Cohen and colleagues reported, they had a median follow-up of 5.5 years, with index participants followed for 10,031 person-years and partners followed for 8,509 person-years. All told, 78 of the initially HIV-negative partners acquired the virus, Cohen said, for an annual incidence of 0.9%. The researchers were able to determine genetic linkage in 72 cases and showed that 46 infections were linked to the index participant – three in the early-treatment group and 43 in the delayed-treatment group.

Cohen said that eight linked infections were diagnosed after the index participant started therapy, three in the immediate treatment group and five among those whose therapy was delayed.

In four cases, including all three in the early treatment group, the diagnosis came within 90 days of the partner starting therapy and analysis suggested the medications had not taken full effect. In the other four cases, the HIV-positive partner had failed therapy when the partner was infected. The first four cases, Cohen commented, “just show that you can’t have unprotected sex the day after you start taking your pills.”

The vast majority of transmissions that were genetically linked to the virus of the index participant occurred in the delayed therapy arm before treatment was started. But about a third of transmissions were not linked to that partner, Cohen said. That implies that people who have unprotected sex with other partners “assume the risk of acquiring HIV in the community, just like everybody else,” he said.

The effect of treatment was “immediate and sustained,” the researchers reported: The incidence of HIV infection in the delayed-therapy group was 36 per 1,731.1 person-years from the beginning of the trial through May 12, 2011, and then fell to 7 per 2,453.6 person-years for the rest of the end of the trial.

According to the report, the study comes just a week after European researchers reported early data from a study of couples – including both heterosexuals and men who have sex with men – who reported not using condoms but whose HIV-positive participants had fully suppressed virus.

In that study, remarkably, there were no cases of HIV transmission, although part of the cohort is still under observation.

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.

Myron S Cohen, Ying Q Chen, Marybeth McCauley, Theresa Gamble, Mina C Hosseinipour, Nagalingeswaran Kumarasamy, James G Hakim, Johnstone Kumwenda, Beatriz Grinsztejn, Jose HS Pilotto, Sheela V Godbole, Suwat Chariyalertsak, Breno R Santos, Kenneth H Mayer, Irving F Hoffman, Susan H Eshleman, Estelle Piwowar-Manning, Leslie Cottle, Xinyi C Zhang, Joseph Makhema, Lisa A Mills, Ravindre Panchia, Sharlaa Faesen, Joseph Eron, Joel Gallant, Diane Havlir, Susan Swindells, Vanessa Elharrar, David Burns, Taha E Taha, Karin Nielsen-Saines, David D Celentano, Max Essex, Sarah E Hudelson, Andrew D Redd, Thomas R Fleming

MedPageToday report
New England Journal of Medicine abstract

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