Pre-exposure HIV-1 prophylaxis with tenofovir alone or in combination with emtricitabine reduces the incidence of HIV-1 infection in healthy heterosexual partners of HIV-1-infected individuals, according to a large study published July 11 in the New England Journal of Medicine.
The findings provide proof of concept that pre-exposure prophylaxis can reduce HIV-1 acquisition in heterosexual populations, and suggest that the strategy may be a useful public health measure together with risk-reduction counseling and other prevention services, wrote Dr. Jared M. Baeten of the University of Washington in Seattle and his colleagues.
Of the 4,747 HIV-1 serodiscordant couples from nine sites in Kenya and Uganda enrolled in the Pre-exposure Prophylaxis (PrEP) study from July 2008 to November 2010, 1,584 and 1,579 of the seronegative partners were respectively randomized to a daily fixed dose of 300 mg of tenofovir (TDF) alone or 200 mg of tenofovir-emtricitabine (TDF-FTC), and 1,584 seronegative partners were randomized to placebo. More than half of the study’s seronegative partners in each study arm were male, including 62%, 64%, and 61% in the monotherapy, combination therapy, and placebo groups, respectively.
After 36 months, the incidence of HIV-1 was reduced by 67% and 75% in the monotherapy and combination groups, respectively, compared with placebo.
As per study protocol, all the seronegative partners had normal renal function, were not infected with the hepatitis B virus, and were not pregnant or breastfeeding. None of the HIV-1 seropositive partners were receiving antiretroviral therapy, nor did they meet Kenyan or Ugandan guidelines for initiation of antiretroviral therapy, the authors reported.
All the participants received a "comprehensive package" of HIV-1 prevention services, including HIV-1 testing and pre- and post-test counseling; screening and testing for sexually transmitted diseases; free condoms with training and counseling; referral for male circumcision; postexposure prophylaxis as per national standards; and the option of hepatitis B virus vaccination (N. Engl J. Med 2012 July 11 [doi: 10.1056/NEJMoa1108524]).
All the seronegative partners had monthly clinic visits during which they underwent HIV-1 and pregnancy testing, individualized adherence counseling, and standardized assessment of sexual behavior and side effects. Serum chemical and hematologic analyses were performed in the first month and then quarterly thereafter. CD4 counts were obtained at 6-month intervals, with referral to local clinics for those who became eligible for initiation of antiretroviral therapy.
During the course of the study, a total of 82 HIV-1 infections were documented in the previously seronegative participants, including 17 in the TDF group, 13 in the TDF-FTC group, and 52 in the placebo group, reflecting incidence rates per 100 person-years of 0.65, 0.50, and 1.99, respectively.
"The HIV-1 protective effects of TDF-FTC and TDF were not significantly different," the authors stated, noting that this finding contradicts those reported in previous studies of animal models. The rates of death, serious adverse events, and serum creatinine or phosphorus abnormalities were similar across the study groups.
When assessed by gender, the efficacy of TDF and TDF-FTC relative to placebo was 71% and 66%, respectively, in women, and 63% and 84% in men, with no statistical difference in the protective effects of either protocol according to sex, the authors observed.
In addition, "protection against HIV-1 was generally similar between subgroup categories for other prespecified subgroup analyses," including age, frequency of unprotected sex with study partner during past month, country, circumcision status of HIV-1 seronegative men, and plasma HIV-1 RNA levels and CD4 counts among the seropositive partner.
Of the participants receiving active treatment, eight were found to have been infected with HIV-1 at baseline, two of whom developed antiretroviral resistance during the study, the authors noted.
"Potential implementation of pre-exposure prophylaxis as a public health measure will require clinical monitoring, methods for encouraging adherence, and ensured access to antiretroviral therapy for HIV-1 infected persons," they wrote.
The trial was funded by the Bill and Melinda Gates Foundation. The authors disclosed no relevant financial conflicts of interest.