Pre-exposure prophylaxis with antiretroviral drugs failed to prevent women in Africa from becoming infected with human immunodeficiency virus (HIV) – apparently because more than half the women failed to take their medication.
The incidence of HIV infection among previously uninfected women treated with a co-formulation of emtricitabine and tenofovir (Truvada) was 4.7 per 1,000 person-years compared with a rate of 5 per 1,000 patient-years among women in the placebo group (P=0.81), said Lut Van Damme, MD, PhD, senior scientist at FHI 360, in Durham, N.C.
In a press briefing here at the Conference on Retroviruses and Opportunistic infections, Van Damme said it was likely that lack of adherence resulted in the failure to show a difference between those women on the active antiretrovirals and those who received placebo.
“The women in the study seriously overestimated adherence,” she said. The participants told researchers that they took their assigned medicine 95% of the time. Pill counts indicated that 85% of the pills were not returned at regular points in the trial. But tests for emtricitabine/tenofovir in the blood of patients showed that only about 40% of the women had levels of the drug that would indicate the pills had been ingested within 48 hours of the tests.
The study was stopped early when an interim analysis showed that it was unlikely to prove positive.
The most effective methods for preventing human immunodeficiency virus (HIV) infection are those that protect against exposure to HIV. Antiretroviral therapy cannot replace behaviors that help avoid HIV exposure (e.g., sexual abstinence, sex only in a mutually monogamous relationship with a noninfected partner, consistent and correct condom use, abstinence from injection-drug use, and consistent use of sterile equipment by those unable to cease injection-drug use). Medical treatment after sexual, injection-drug-use, or other nonoccupational HIV exposure is less effective than preventing HIV infection by avoiding exposure.
In July 1997, CDC sponsored the External Consultants Meeting on Antiretroviral Therapy for Potential Nonoccupational Exposures to HIV. This panel of scientists, public health specialists, clinicians, ethicists, members of affected communities, and representatives from professional associations and industry evaluated the available evidence related to use of antiretroviral medications after nonoccupational HIV exposure. In 1998, DHHS issued a statement that outlined the available information and concluded that evidence was insufficient about the efficacy of nonoccupational postexposure prophylaxis (nPEP) to recommend either for or against its use.
Since 1998, additional data about the potential efficacy of nPEP have accumulated from human, animal, and laboratory studies. Clinicians and organizations have begun providing nPEP to patients they believe might benefit. In certain instances, health departments have issued advisories or recommendations or otherwise supported the establishment of nPEP treatment programs in their jurisdictions . In May 2001, CDC convened the second external consultants meeting on nonoccupational post-exposure prophylaxis to review and discuss the available data. This report summarizes knowledge about the use and potential efficacy of nPEP and details guidelines for its use in the United States.† The recommendations are intended for nonoccupational exposures and are not applicable for occupational exposures.
The so-called FEM-PrEP was a randomized, double-blinded, placebo-controlled trial of once-daily oral emtricitabine/tenofovir. The primary effectiveness endpoint was incident HIV infection during 52 weeks of follow-up.
Participants attended screening, enrollment, and follow-up visits monthly. HIV seroconverters were taken off the product and followed for an additional 52 weeks
“We do not have evidence that the women were giving the pills to others or sharing the pills. There were many women in the trial who did not perceive themselves to be at risk,” Van Damme noted. She said that other reasons might also exist that caused the women not to take the medications.
Antiretroviral Therapy as Pre-Exposure Prophylaxis
Researchers long-ago established that antiretroviral drugs reduce the risk of mother-to-child transmission of HIV, as well as the risk of post-exposure occupational transmission. Today, they are exploring the prevention of HIV infection in a new way, driven by this question: Can the antiretroviral drugs now used to treat HIV infection also be used to reduce the risk of HIV infection in HIV-negative but high-risk individuals? Given that an HIV vaccine is still unavailable and that millions of new infections continue to occur annually worldwide, this is an important public health question that needs to be answered.
The antiretroviral drugs that are currently being tested as prophylactic agents against HIV infection in humans and in other animals are tenofovir and emtricitabine. Tenofovir, a nucleotide analogue, was approved for therapeutic use by the United States Food and Drug Administration in 2001. Emtricitabine, a nucleoside analogue, was approved in 2003. Both drugs are taken once daily, with or without food, and are sold in a combined form as Truvada® in the United States.
Data derived from recent animal studies involving rhesus macaques and humanized BLT mice support the merits of using antiretroviral drugs as pre-exposure prophylaxis (PrEP) against HIV infection. Because the animals that were treated with tenofovir alone or with a combination of tenofovir and emtricitabine were protected at least partly - if not completely - against oral, rectal, or vaginal challenges of virulent SIV (rhesus macaques) or HIV-1 (humanized BLT mice), researchers believe that PrEP might slow the spread of HIV in high-risk human communities.
By Paul Simmons, R.N.
From The Center for AIDS
The study aimed at determining if pre-exposure prophylaxis with the antiretroviral combination would prevent the women from seroconverting to positive HIV status. Data were collected on 2,056 women, about half of whom were in each group.