The presentation of the detailed findings of HPTN 052 by Dr. Myron Cohen, the study’s principal investigator, and his colleagues was greeted with a standing ovation by a packed room at the 2011 International AIDS Conference in Rome on Monday. The stunning finding of a more than 96 percent reduction in transmission risk for discordant couples where the HIV-infected partner was randomized to early antiretroviral therapy (ART) at CD4 counts of 350-550 compared to couples where ART was delayed for the infected partners until CD4 counts dropped to 250 or less, makes ART the most effective prevention intervention identified to date.
Although the broad strokes of the trial design and results had been well reported soon after the study was stopped on April 28, this first presentation to a scientific audience offered new details. All of the particulars can be found in an article published online Monday in The New England Journal of Medicine.
Much greater detail was offered on the clinical sites and the demographics of the participants: 278 couples from the Americas, 954 from Africa and 531 from Asia. Sixty-three percent of the participants were between 26 and 40 years old. Fifty-two percent of the couples in the study are from sub-Saharan Africa and the African sites had greater numbers of younger participants—aged 18 to 25 years old, and a greater proportion of HIV-infected women—58 percent compared to 49 percent in the trial overall. Ninety-four percent of all the couples in the study were married.
There were 39 HIV transmission events in the study – four in the immediate treatment arm and 35 in the delayed treatment arm. Eighty-two percent of all of the HIV transmission events occurred among African couples. Of these, there were 28 “linked” events – meaning the HIV transmission to the originally uninfected partner occurred within the study couple – seven unlinked events and three transmission events still under examination, all of which occurred in the delayed treatment arm.
Of the 28 linked transmission events, only one HIV transmission occurred in the early treatment arm and additional analysis confirms that this transmission occurred either before the infected patient began ART or very early in treatment before viral suppression had occurred. Sixty-four percent of the HIV transmissions were from female to male partners and notably, 61 percent of the linked HIV infections were transmitted from partners with CD4 counts greater than 350.
In addition to evaluating the prevention benefits of ART, HPTN 052 also served as an evaluation of early ART on clinical outcomes of the HIV-infected partners. The findings on this question were also clear—HIV-infected partners in the early treatment arm enjoyed greater clinical benefits compared to the HIV-infected partners for whom treatment was delayed. There was a 41 percent lower risk of experiencing a clinical event for those in the immediate treatment arm.
The most common clinical event in both arms was tuberculosis, and there was an 84 percent reduction in the incidence of extra pulmonary tuberculosis between the immediate and the delayed treatment arms. Specifically, there were 17 cases of extra pulmonary tuberculosis in the delayed treatment arm compared to three cases in the immediate arm. Fifty-five percent of the extra pulmonary TB cases occurred in India. Only four percent of the HIV infected trial participants in both arms were receiving isoniazid preventive therapy (IPT), despite World Health Organization guidelines recommending IPT for persons with HIV who do not present with TB disease.
According to Cohen, “These results can and should inform HIV test and treat strategies.”