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SEATTLE -- Daily emtricitabine/tenofovir alafenamide (F/TAF, Descovy) was non-inferior to emtricitabine/tenofovir disoproxil fumarate (F/TDF, Truvada) for pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM), a researcher said here.

In what was described as the first HIV prevention trial without a placebo arm, HIV incidence rate was 0.16 per 100 person years in the F/TAF arm and 0.34 per 100 in the F/TDF arm, which met the margin of non-inferiority (IRR 0.47, 95% CI 0.19-1.15), reported Charles Hare, MD, of Kaiser Permanente San Francisco Medical Center.

The broad 95% confidence interval that spanned 1.0 meant, however, that F/TAF could not be called superior despite the two-fold difference between the point estimates.

Secondary outcomes, which were bone and renal safety, did significantly favor F/TAF over F/TDF, according to the phase III , a late-breaking presentation at the Conference on Retroviruses and Opportunistic Infections (CROI).

Speaking to 番茄社区app prior to the conference, CROI vice chair Sharon Hillier, PhD, of the University of Pittsburgh, called it "the dawn of a new age in prevention studies."

At the press conference, Hillier elaborated on this, noting that this study had the fewest HIV endpoints of any modern-era prevention study.

"It's a brave new world for those of us in prevention, thinking about how to actually do these studies and appropriate ways to contextualize the results," said Hillier, who moderated the press conference, but was not involved with the research.

But some members of the media threw cold water of real-world healthcare costs on this sunny new outlook, questioning the increased cost of F/TAF compared to F/TDF, especially because Truvada is due to go off patent in 2021. Moreover, it was asked whether F/TAF would end up costing the healthcare system more money when there may be no real difference in clinical outcomes.

Hare responded that he could not address financial considerations, adding that finding clear differences in clinical outcomes between the two therapies would require a huge number of people and a long observation time.

Study Details

Researchers randomized about 5,400 MSM, including transgender women, who were at high sexual risk of HIV (defined as ≥2 episodes of condomless anal sex in the past 12 weeks or diagnosis of rectal gonorrhea/chlamydia or syphilis in the past 24 weeks to receive either F/TAF or F/TAF for 96 weeks as PrEP.

This study was conducted in North America and the European Union, in cities/sites with high HIV incidence, researchers noted. The primary endpoint was the HIV infection rate when 50% completed 96 weeks.

Demographic characteristics were similar between groups, with a median age of 34, 84% white, and 1%-2% transgender women. About 60% had engaged in ≥2 acts of receptive condomless anal sex in the last 12 weeks, and two-thirds of both groups reported recreational drug use in the last 12 weeks.

Renal safety was assessed with estimated glomerular filtration rate and ratio of proximal tubular protein to creatinine. The F/TAF arm did significantly better than the F/TDF group on both. With regard to bone effects, patients on F/TDF showed approximately 1% decline in bone mineral density during the study, whereas slight increases were seen with F/TAF.

Seven infections occurred in the F/TAF group and 15 in the F/TDF group. Hare noted that only one participant in each arm had drug levels "determined to be adequate for protection," and most were infected prior to study entry or had lower levels of medication via dried blood spot analysis.

Myron Cohen, MD, of the University of North Carolina at Chapel Hill, noted the low incidence of HIV infections, and said there were several explanations, including the idea that PrEP agents prevented "substantial numbers of cases of HIV."

"This shows the difficulty of developing new PrEP agents when the comparator demonstrates the proven efficacy of TDF/FTC PrEP," Cohen, who was not involved with the research, told 番茄社区app. "But this work is the first to be presented in the era where TDF/FTC serves as a comparator, so it deserves great attention."

Examining safety, both drugs were considered safe, with 93 adverse events per arm, and around 20 per arm considered study drug-related. Five and six serious adverse events occurred in study arm, and three deaths total.

At the press conference, Hillier asked Hare about other sexually transmitted infections, and he responded that 57% had at least one additional STI, with "high rates" of rectal gonorrhea, chlamydia, and syphilis.

"This indicated these were the right participants to be enrolled in the study, and the risk behavior continued over the study period," Hare said.

Secondary outcomes included bone safety at week 48 (via a bone mineral density substudy), where the improvement favored the F/TAF arm, and renal safety through week 48, where Hare said there was a "small, but significant difference" favoring the F/TAF arm.

When discussing how this could impact future studies, Hillier commented at the press conference that there may be questions about how to interpret data that don't reference placebo.

"Embrace that it's non-inferior. Those days [of placebo-controlled prevention trials] are behind us now," she said.

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