Assessing individual patient crucial when prescribing PrEP

SAN DIEGO — With three new studies this past year and the FDA approval of combination tenofovir/emtricitabine, pre-exposure prophylaxis has been a hot topic, according to a presentation here at ID Week 2012.

Judith Aberg, MD, Jeffrey Bergstein Professor of Medicine at New York University Langone Medical Center, discussed the three recent pre-exposure prophylaxis (PrEP) trials and what infectious disease specialists should consider when they make the decision to prescribe PrEP for a patient.

The first trial was the Partners PrEP trial. Seronegative partners in serodiscordant couples were randomly assigned to three groups: placebo, tenofovir (Viread, Gilead) or combination tenofovir/emtricitabine (Truvada, Gilead). The results showed that both tenofovir and combination tenofovir/emtricitabine resulted in a significant reduction in the transmission of HIV.

The second study, TDF2, was the second phase of the CDC study TDF1, which tested monotherapy for PrEP. During TDF1, there was a suggestion that combination therapy would be better, so the protocol was revised to TDF2. The HIV-negative partners in serodiscordant heterosexual couples were randomly assigned to placebo or combination tenofovir/emtricitabine. The trial closed early because of a low retention rate, but the data showed that the combination treatment resulted in a significant reduction in the acquisition of HIV.

The last trial was the FEM PrEP study, which included HIV-negative women from Kenya, South Africa and Tanzania who were considered high risk. The women were randomly assigned to combination tenofovir/emtricitabine or placebo. In this trial, there was no significant difference in HIV acquisition between the arms.

“Why do we see these conflicting results?” Aberg said. “One of the reasons is difference in adherence. There were numerous pregnancies in the FEM PrEP trial, even among women who reported using oral contraceptives. This implies that it might be an adherence issue. We need to learn more about this population to understand their perception of risk. It may be that they did not see themselves at enough risk to take the medicine.”

Aberg said the tenofovir levels in patients in the Partners PrEP trial and TDF2 were higher, and there was more efficacy. Other factors that could be causing the conflicting results include differences in age, gender, routes of HIV entry and sexually transmitted infections.

She said there are many unanswered questions about how to roll out PrEP in practice.

“As clinicians, we’re going to have patients coming in inquiring about PrEP,” Aberg said. “One of the things that we must do is determine exactly who the target population is and what is the duration of treatment.”

She said clinicians must make the assessment of the risk in each individual patient. Before prescribing PrEP, it is also important to ensure that the patient is HIV-negative and does not have acute HIV. Those who acquired resistance in the trials already had HIV, but the disease was not established on the HIV antibody test.

Interim guidelines for PrEP were updated in August. The updates mostly relate to pregnancy and breast-feeding, Aberg said. Women on PrEP should receive pregnancy tests, and if women become pregnant, it is important to assure them of the drug’s safety.

“According to data from ART pregnancy registry, tenofovir appears safe in pregnant women,” she said. “But this is a different population. The CDC is cautioning us about the importance of having this discussion about PrEP with women considering getting pregnant.”

Regarding safety, Aberg said, for the most part, tenofovir appears to be safe. But it is necessary to find out what the long-term complications may be.

For more information:

Aberg J. What’s Hot in HIV Clinical Science. Presented at: ID Week 2012; Oct. 16-19; San Diego.

Disclosure: Aberg reports financial relationships with Janssen, Merck, Tibotec and Viiv.