ROME – The risk of sexually transmitted HIV was reduced by 96% when the infected partner received a combination of three or more antiretroviral drugs immediately following detection of HIV infection, according to the findings of a randomized controlled trial known as HPTN 052.
These striking results offer "definitive proof of a concept," lead trial investigator Dr. Myron S. Cohen of the University of North Carolina at Chapel Hill said July 18 at the International AIDS Society Conference on HIV Pathogenesis and Treatment.
The study researchers received a prolonged standing ovation at the meeting, where the results were presented in their entirety for the first time. The findings were simultaneously published online July 18 in the New England Journal of Medicine (2011 [10.1056/NEJMoa1105243]).
The concept behind early initiation of antiretroviral therapy (ART) in HIV-positive members of serodiscordant couples, a strategy dubbed "treatment as prevention," had been hypothesized based on known virology and pharmacology, Dr. Cohen said, but the evidence that early initiation of antiretroviral therapy prevents infection "is obviously thrilling."
Photo credit: Steve Forrest/Worker's Photos
Dr. Myron S. Cohen
In their study, Dr. Cohen and his colleagues enrolled 1,763 mostly heterosexual serodiscordant couples in several African countries, Brazil, India, Thailand, and the United States. The HIV-infected partners were randomly assigned to either immediately start triple or quadruple antiretroviral therapy, regardless of CD4 count, or to a deferred-treatment group that started therapy only after their counts dropped below 250 cells/mcL, or they developed pneumocystis pneumonia, or another AIDS-related event. All couples received information and counseling about safe sex and were treated for any HIV-related complications.
At the end of the 20-month study period, 39 previously uninfected partners became infected with HIV. Of these, 28 infections were shown by genetic analysis to be linked, meaning they were transferred from the known infected member of the couple and not a different partner. The vast majority of linked transmissions (27) occurred in the delayed-treatment arm of the study. Only one linked transmission occurred in the immediate-treatment arm.
This highly significant difference corresponded to a 96% risk reduction attributed to immediate therapy, and spurred the independent data and safety monitoring board’s recommendation in April that the deferred-treatment arm be stopped early. The study results initially were reported earlier this year by the National Institute of Allergy and Infectious Diseases, which sponsored the study.
Dr. Cohen encouraged physicians to talk to their patients about the results, which are expected to soon influence treatment guidelines for serodiscordant couples.
He also said that physicians should counsel patients that the infected partner must be on suppression therapy for at least several weeks before unprotected intercourse is attempted, though partners should be encouraged to continue using condoms. ART adds a benefit that is "superimposed" onto the benefits of condoms, he said.
In a related presentation, Dr. Mina C. Hosseinipour of the University of North Carolina Chapel Hill, and a site investigator for the study in Malawi, discussed her analysis of trial outcomes by region.
Some 82% of the transmissions, linked and unlinked, occurred at African study sites, despite the fact that African sites accounted for only 54% of trial participants. This, Dr. Hosseinipour said, related to a combination of factors, including baseline HIV RNA and CD4 counts, HIV subtype, adherence and response to ART, self-reported sexual behavior, and differential timing of ART initiation in the delayed arm.
Self-reported sexual behavior was different in the African sites, Dr. Hosseinipour said, where 29% of the HIV-infected partners reported three or more sex acts in the previous week, compared with 18% at the Asian and American sites. A greater proportion of HIV-infected partners at the African sites – 9% – were more likely to report unprotected sex in the previous week, compared with 4% elsewhere.
Adherence to ART regimens was uniformly high at 99% across regions, Dr. Hosseinipour reported.
The important question of how to use the trial results and when to initiate ART was addressed in a separate presentation by Dr. Beatriz Grinsztejn of the Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz in Brazil.
While Dr. Grinsztejn acknowledged that there remains some controversy about when to initiate ART, the new trial evidence demonstrated a 41% reduction in the number of HIV-related adverse events, including tuberculosis, bacterial pneumonias, severe bacterial infections, and death, among HIV-infected individuals in the immediate-treatment arm. For example, there were 17 cases of tuberculosis in the immediate-ART arm versus 33 in the delayed-treatment arm.
This means that early ART represents a "true benefit to the person taking it and not just [to] the partner," she said.