TDF2 OLE: High PrEP adherence results in zero infections

Issue: August 2015

Heterosexual men and women in Botswana were highly adherent to pre-exposure prophylaxis, resulting in no new HIV infections during the course of 12 months, according to results from the the CDC’s TDF2 open-label extension trial.

The findings are welcome news for HIV researchers in light of recent failures to demonstrate the efficacy of PrEP among women in other clinical trials — largely due to participants’ poor adherence to the study drug. Moreover, the TDF2 open-label extension trial may be more representative of real-world settings because its participants had received no compensation and were aware they were taking an active drug rather than a placebo, according to study researcher Allan W. Taylor, MD, MPH, team lead for the clinical trials team in the CDC’s Division of HIV/AIDS Prevention.

“Our analysis found high adherence to daily PrEP among most men and women at high risk for HIV,” Taylor told Infectious Disease News. “Subanalysis of women in the study showed that they were highly adherent to daily dosing. To us, this offers reassurance in the wake of the other recent studies we’ve seen — like VOICE, FEM PrEP and FACTS 001 — that showed that women hadn’t experienced protection against HIV because they weren’t taking PrEP as prescribed.”

Open-label extension
Starting in 2007, CDC researchers conducted the TDF2 trial — a randomized, double blind, placebo-controlled study of daily oral Truvada (tenofovir disoproxil fumarate/emtricitabine, Gilead Sciences; TDF/FTC). The study included more than 1,200 young heterosexual adults in Gaborone and Francistown, Botswana. According to the CDC, approximately 22% of people aged 15 to 49 years are living with HIV in the country.

Results demonstrated that PrEP reduced the risk for HIV infection by 63%. Between February and May 2013, the researchers began conducting an open-label extension of TDF2, offering former participants (n = 229) TDF/FTC for up to 12 months. They were tested regularly for HIV, and in addition to the use of self-reports, dried blood spots (DBS) were collected on a monthly basis to measure their adherence to the regimen. Researchers analyzed DBS data for 120 participants at the time of presentation.

Previously, self-reports of adherence have been overinflated. For example, in the VOICE trial, adherence to PrEP was about 86% to 90% based on self-reports and the number of unused tenofovir (TFV) products. However, 3 months into the trial, less than 40% of women taking some form of TFV-based regimen had detectable levels of the drug in plasma, and majority of these women had no detectable TFV during subsequent visits, according to the trial’s investigators.

Encouraging findings
Results of the open-label extension, presented today at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Vancouver, British Columbia, showed that 87% of participants reported taking TDF/FTC each day for the past 3 days. According to the researchers, 58.3% reported “very good” adherence in the past 30 days, and 32.3% reported “good” adherence.

However, unlike the VOICE trial, DBS testing showed that participants’ high levels of self-reported adherence were reflective of their actual use of the study drug. Men and women had detectable levels of the drug at 93% of visits, and the overall proportion of adults with detectable mean TFV levels higher than 25 ng/mL was 95%, 93%, 94% and 91% at months 3, 6, 9 and 12, respectively. Among participants who underwent DBS testing, women had detectable levels of the drug at 87% of visits and men at 96%.

Taylor said the high adherence rate among both men and women in the study may be due to the fact that participants understood the effectiveness of PrEP and had volunteered to receive it.

According to the researchers, there was no evidence of risk compensation associated with PrEP in the study. In fact, sexual risk behavior decreased during the course of 12 months, with the number of reported sex partners in the last 30 days declining by 12%, and the number of condomless sex acts dropping 39%.

In addition, Taylor and colleagues reported there were no new HIV infections during the study.

Taken together with encouraging results from the ADAPT trial in Cape Town, which is examining three different methods of delivering PrEP, the findings support the expansion of PrEP in resource-limited settings, according to the researchers.

“PreP is a highly effective HIV prevention strategy when taken consistently,” Taylor said. “Encouragingly, the study shows that it’s practical to expect that those at risk can adhere closely to their PrEP regimens.

“The findings underscore the important role of PrEP in protecting the health of those at substantial risk for HIV, especially of women, with women and girls accounting for more than half of people living with HIV worldwide, and 10,000 new infections occurring among women each year in the U.S. alone. Prevention is key, and PrEP provides a much-needed female controlled method that can be especially valuable to those who are unable to negotiate condom use.”

Taylor said that in the U.S., health care providers are in a key position to increase “awareness and uptake of safe and effective PrEP.” – by John Schoen

Reference:
Henderson F, et al. Characteristics and Oral PrEP Adherence in the TDF2 Open-Label Extension in Botswana. Presented at: International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 19-22, 2015; Vancouver, British Columbia.

Disclosure: Gilead Sciences provided the study drug but played no role in the analysis or findings. Taylor reports no relevant financial disclosures.