HIV-infected men and women with relatively healthy immune systems who received immediate oral antiretroviral therapy (ART) were 96.3% less likely to pass on the infection to their uninfected partners and remained healthier than those whose treatment was delayed, according to a multinational clinical study.
Though set to run until 2015, the Phase 3 clinical trial (HPTN 052) was halted early by an independent data safety monitoring board after finding unequivocally that early ART provided sexual partners substantial protection from acquiring HIV. Antiretroviral therapy will be offered to the HIV-infected persons in the delayed treatment arm and study participants will be followed for at least one year.
"This is excellent news," said Myron Cohen, MD, a Fellow of the American College of Physicians and the study's principal investigator, "The study was designed to evaluate the benefit to the sexual partner as well as the benefit to the HIV-infected person. This is the first randomized clinical trial to definitively indicate that an HIV-infected individual can reduce sexual transmission of HIV to an uninfected partner by beginning antiretroviral therapy sooner."
HPTN 052 enrolled 1,763 HIV-serodiscordant couples, 97% of whom were heterosexual. The study was conducted at 13 sites across Africa, Asia and North and South America. HIV-infected participants were determined to be relatively healthy by a CD4 cell count between 350 and 550 cells/mm3 and the absence of any AIDS-related events such as Pneumocystis pneumonia within 60 days of entering the study. The HIV-uninfected partners all tested negative for the virus within 14 days of entering the study. All participants were at least 18 years of age and the median age was 33 years at the time of enrollment, 52% of the participants were male, and the couples agreed to participate in the trial for five years.
886 couples were randomly assigned to receive a three-drug HIV treatment combination, and 877 were assigned to deferred treatment, where the HIV-infected partner received ART only after his or her CD4 count dropped below 250 cells/mm3 or an AIDS-related event occurred. Both groups received regular HIV testing, safe-sex counseling, free condoms, testing and treatment for sexually transmitted infections, and treatment for any HIV-related complications.
Among the 877 couples in the delayed ART group, 27 HIV transmissions occurred, and in the immediate treatment arm, one transmission occurred. Genetic analysis confirmed that the source of the new infection was the previously HIV-infected partner.
In the originally HIV-infected individuals themselves, 17 cases of extrapulmonary tuberculosis occurred in the delayed ART group, compared with 3 cases in the immediate ART group. There were also 23 deaths during the study, 13 in the delayed ART group and 10 in the immediate ART group.
"Previous data about the potential value of antiretrovirals in making HIV-infected individuals less infectious to their sexual partners came largely from observational and epidemiological studies," said National Institute for Allergy and Infectious Diseases (NIAID) Director Anthony S. Fauci, MD, a Master of the American College of Physicians. "This new finding convincingly demonstrates that treating the infected individual, and doing so sooner rather than later, can have a major impact on reducing HIV transmission."
The trial is conducted by the HIV Prevention Trials Network and funded by the NIAID. The 11 antiretroviral drugs used in the study in various combinations were made available by their manufacturers.
"With these results we should redouble our efforts to diagnose individuals with HIV earlier," said HIV Medicine Association Chair Kathleen Squires, MD, a Fellow of the American College of Physicians. "The U.S. federal treatment guidelines were modified recently to recommend earlier treatment for people with HIV infection to improve health outcomes for this patient population. We now have further evidence that effective treatment not only benefits the individual but also will help reduce the spread of this disease."