SEATTLE – Descovy [emtricitabine/tenofovir alafenamide (F/TAF]) was noninferior to Truvada [emtricitabine/tenofovir disoproxil fumarate (F/TDF)] for preexposure HIV prophylaxis in a blinded, involving more than 5,000 men at high risk for the infection.
Both nucleotide reverse transcriptase inhibitors are made by Gilead, and the company funded the trial.
F/TDF (Truvada) has been a blockbuster for the company, both for HIV treatment and, since 2012, for preexposure prophylaxis (PrEP); it’s the only medication to carry the indication. However, F/TDF is set to go off patent in 2021, so the company has turned its development efforts to a successor, F/TAF (Descovy), a prodrug of tenofovir that is already approved for HIV treatment.
The new study builds a case for F/TAF for PrEP, but whether the results are strong enough to persuade people to opt for it over a much less expensive generic version of F/TDF remains to be seen.
The trial randomized 2,694 men who have sex with men to F/TAF, and 2,693 to F/TDF for up to 96 weeks. Entrance criteria included at least two episodes of unprotected anal sex in the previous 12 weeks, or a diagnosis of rectal gonorrhea, chlamydia, or syphilis in the previous 6 months.
More than half the men contracted at least one sexually transmitted infection during the trial, “which indicated to us that these were the right patients to be enrolled in the study,” lead investigator Charles Hare, MD, an infectious disease specialist at the University of California, San Francisco, said at the Conference on Retroviruses and Opportunistic Infections.
There were 15 new HIV infections in the F/TDF group (0.34 per 100 person-years), versus 7 in the F/TAF group (0.16 per 100 person-years). Almost all of the new infections were due to poor adherence – as proven by blood levels and dry blood spot testing – and most of the rest were in men who probably entered the trial with newly acquired HIV.
When those subjects were excluded, there were just two new onset HIV cases in subjects adherent to dosing, one in each arm. Infection rates were far lower than would have been expected had the subjects not been on PrEP.
One of Gilead’s main selling points for F/TAF over F/TDF is that the newer drug has better bone and renal safety, and there were slight biomarker differences in the trial that supported the assertion.
For instance, spine bone mineral density decreased 3% or greater from baseline in 10 F/TAF patients, but 27 men on F/TDF (P less than .001). Results were similar with hip bone density.
On the renal front, estimated glomerular filtration rates fell a median of 2.3 mL/min per 1.73 m2 in the F/TDF arm, but rose 1.8 mL/min per 1.73 m2 in men on F/TAF (P less than .001). Proximal tubular protein to creatinine ratios were largely unchanged from baseline with F/TAF, but slightly higher in the F/TDF group, at 48 weeks.
There were no statistically significant differences on actual safety outcomes – as opposed to biomarkers – between the two drugs or discontinuations due to side effects, which were rare and most often due to gastrointestinal issues. F/TAF patients gained about 1.1 kg in the trial, while weight held steady in the F/TDF arm. The study team plans to analyze lipid profile differences between the groups, since concern has been raised about F/TAF’s effect on them.
In a press conference at the conference, there was quite a bit of discussion about whether the results would justify using F/TAF for PrEP when less expensive generic versions of F/TDF become available.
“That’s a great question,” Dr. Hare said. “Both drugs actually performed quite well,” and both “do pretty well in terms of safety in this population.”
It’s not known at this point if the biomarker differences will prove to be clinically relevant. Hip fractures, kidney failure, and other problems are so rare in young, relatively healthy PrEP users that a trial to demonstrate clinical relevance would have to be huge, with years-long follow-up, Dr. Hare noted.
The average age of the men in this study was 36 years. Most were white, and about 60% lived in the United States. Other participants were from Canada or Europe.
The work was funded by Gilead; five investigators, including the senior investigator, were employees. Dr. Hare is an investigator for the company.
SOURCE: Hare CB et al. CROI 2019, Abstract