HIV incidence rates in MSM and transgender women taking F/TAF or F/TDF were found to be very low and significantly less than the rate in at-risk individuals not on PrEP in the US.
When taken daily, emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV pre-exposure prophylaxis (PrEP) has a high success rate of preventing HIV infection.
When compared with TDF for HIV treatment, tenofovir alafenamide (TAF) has higher intracellular tenofovir-diphosphate levels, lower plasma tenofovir levels, and is associated with improved renal and bone safety.
Now, investigators have set out to research the efficacy and safety of F/TDF (Truvada) when compared with emtricitabine/tenofovir alafenamide (F/TAF; Descovy) in the DISCOVER study.
The study, which enrolled cisgender-men who have sex with men (MSM) and transgender women who are at high risk for HIV acquisition, was presented in a late-breaking oral abstract session at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019) on Wednesday, March 6, 2019.
In an exclusive interview with Contagion®, Brad Hare, chief of infectious disease at Kaiser-Permanente, San Francisco, and lead presenter of the trial data, explained the biggest takeaways from the study (see video).
The study was a randomized, double-blind, active-controlled investigation that was conducted in North America and Europe at sites with high HIV prevalence in MSM.
Entry to the study required >2 episodes of condomless anal sex in the past 12 weeks or the diagnosis of rectal gonorrhea/chlamydia or syphilis in the past 24 weeks. In total 5387 adults were enrolled and treated at 94 sites in 11 countries with 3226 (60%) treated in the United States.
The mean age of the participants was 36 years (range 18-76), 9% of those enrolled were black, and 1% of participants identified as transgender women. According to study data, 23% of participants reported prior PrEP use and 41% of participants reported >3 receptive condomless anal sex partners in the 90 days prior to study enrollment.
For the study, the participants received daily blinded F/TAF (200/25 mg) or F/TDF (200/300 mg), with matching placebo; the investigators conducted pill counts and analyzed blood levels to measure adherence. Additionally, renal safety was evaluated and 3 anatomic-site sexually transmitted infection (STI) tests were administered every 12 weeks. Risk behavior was also assessed at those time points.
The primary endpoint of the DISCOVER study was the HIV infection rate per 100 person years when 50% completed at 96 weeks.
The investigators used the US Centers for Disease Control and Prevention HIV surveillance data to calculate the background HIV incidence rate in at risk individuals who were not on a PrEP regimen from 105 metropolitan statistical areas for comparison.
In the DISCOVER study, 90% of participants completed >48 weeks on the study with median follow-up of 84 weeks. For this analysis, 85% of the participants remained on the study drug, 6% of participants discontinued by choice, and an additional 6% of participants were lost to follow-up. Both drugs were noted to be well-tolerated with 1.5% adverse event-related discontinuations.
According to the study team, “on-study sexual HIV risk persisted with an STI rate of 99.5 per 100 person years.”
Across both of the treatment arms there were 21 HIV diagnoses documented, which is an infection rate of 0.26 per 100 person years. The investigators note that this figure significantly is lower than the expected HIV infection rate for those at risk for HIV but not on PrEP in the United States.
"What we were able to determine from this study is that Descovy is non-inferior in its efficacy for PrEP compared to Truvada," Dr. Hare told Contagion®. "We also had some pre-specified secondary endpoints looking at safety parameters, specifically bone and renal safety using these drugs, and we found a significant difference between the arms that favored the Descovy product over Truvada."
“In a multinational population of cis-MSM and transgender women at risk of sexual HIV infection, the HIV incidence rate on either F/TAF or F/TDF was very low and significantly less than the background rate in those at risk but not on PrEP in the United States,” the investigators conclude, highlighting that in nearly 2 years of follow-up, both F/TAF and F/TDF, given daily, were well-tolerated and had low discontinuation rates.
The study, “The Phase 3 DISOVER Study: Daily F/TAF or F/TDF For HIV Pre-exposure Prophylaxis,” was presented at CROI 2019 on Wednesday, March 6, 2019 in Seattle, Washington.