SEATTLE — The addition of tenofovir alafenamide fumarate (TAF) to emtricitabine (Descovy, Gilead Sciences) is noninferior to the addition of tenofovir disoproxil fumarate (TDF, Truvada, Gilead Sciences) for HIV prevention, according to interim results from a multicenter study of nearly 5000 gay and bisexual men and transgender women.
It is great to have the option, but the impact this will have in practice in the United States is not clear, said Brad Hare, MD, from Kaiser Permanente San Francisco.
"I think we're going to be grappling with this for a while," he told Medscape Medical News.
"There are some clear-cut situations where Descovy is great," such as for patients with moderate renal impairment, he explained here at the Conference on Retroviruses and Opportunistic Infections 2019.
But, he asked, "do these data suggest that the safety benefits we're getting indications of with TAF are large enough to warrant wholesale switchovers" to this new combination? "I don't know that that's the case."
Concerns about the study design and statistical analysis, combined with the high cost of the drug, have left many physicians wondering how valuable Descovy will be as progress is made in the move to end HIV in the hardest-hit communities in the United States.
Truvada is the only drug currently approved for pre-exposure prophylaxis (PrEP) by the US Food and Drug Administration. But ever since Gilead Sciences unveiled the Descovy combination with TAF— a tenofovir prodrug that builds to higher concentrations faster than TDF and has no renal or bone mineral density effects — people have been wondering how it would compare with the Truvada combination.
To find out, Hare and his colleagues at sites in Canada and Europe launched their study, sponsored by Gilead Sciences. Because it would be unethical to test the effectiveness of PrEP with TAF, they designed a noninferiority study to compare Descovy with Truvada.
The 5387 participants at high risk for HIV were randomized to receive one of the two combinations. They were monitored with blood tests to establish adherence and followed for 96 weeks.
Findings from the first half of the participants to complete the study — which Hare presented — were both surprising and not surprising, he said.
"Going in, we expected TAF would be noninferior to TDF," he noted, which is exactly what they found. But there were some problems.
The good news was that only 22 people acquired HIV during the study, largely as a result of nonadherence. But that was the bad news, too.
The assumption going into the study was that 144 participants might acquire HIV. This would give the study sufficient power to say with a 99% confidence interval that Descovy worked at a level on par with Truvada. But with only 22 infections, the confidence interval dropped.
And there was one puzzling finding: 15 of the 22 infections were in the Truvada group and only seven were in the Descovy group.
We had expected the infections to be spread evenly across the two groups. But "if those 22 infections had been more evenly distributed, we couldn't have shown noninferiority," said Hare.
Statistically, "the data clearly demonstrate noninferiority, even with the smaller number of infections," he added.
Skepticism and Questions
"This is kind of an unusual study design," said Joseph Eron, MD, from the University of North Carolina at Chapel Hill.
The findings left Wendy Armstrong, MD, from the Emory University School of Medicine in Atlanta, wondering whether Descovy would help her patients. She pointed out that the patent on Truvada is expected to expire soon. Meanwhile, Descovy will be under patent for the foreseeable future.
And that means, Armstrong noted, that switching patients to Descovy could have a high price tag.
"The big picture here is that we have an out-of-control HIV epidemic, and as much as I hate to think about cost as a physician, I think we have to," she said. "When I look at the small clinical difference that may or may not be significant in bone and renal health for a drug that's not taken every day for the rest of their lives, I don't know that that's important."
The question of how important Descovy will be on the ground for those currently not receiving PrEP seemed to be on the minds of many people in the auditorium, who wanted to know whether Descovy worked as well for black participants as white participants.
Black Americans make up the vast majority of people at risk for HIV, but represent only 1% of those currently taking PrEP, as previously reported by Medscape Medical News.
Were baseline data adjusted to account for the higher HIV rates in black communities?, asked Carlos del Rio, MD, from Emory University.
Had the researchers looked at the race of the people in the study who acquired HIV?, asked Eron.
They hadn't done either yet, Hare acknowledged, but that information will be included in future reports.
"That obviously has to be done," Eron said.
Bringing PrEP to All
Charlotte-Paige Rolle, MD, from the Orlando Immunology Center in Florida, was thinking about that, too. She said she is concerned that if black men who have sex with men and black trans and nontrans women are not included in studies, what works for these populations will never be established. One in 10 participants was a black man who has sex with men, 1% of the study cohort was transgender, and none of the participants were cisgender women.
"We can't afford to be studying what will probably be a very important HIV prevention intervention in a population that does not need it the most," said Rolle. "I put the onus on the study's sponsors. They probably needed to have done more to get those individuals into this study."
For her part, Rolle already has patients at her private clinic asking about Descovy for PrEP. She tells them she hopes it will be approved soon "because it seems to have some safety advantages."
But then she thinks about the young gay and bisexual black men she saw in a study she was involved with (Int J STD AIDS. 2017;28:849-857) who either didn't get on PrEP in the first place or quickly stopped taking it, and wonders whether having a second PrEP option that is so similar to the first will make a difference.
"If you look at the priority populations for PrEP — for instance, minority men who have sex with men — there are actually very few discontinuations of PrEP due to side effects," she said.
When it comes to the campaign to end HIV by 2030 by targeting communities strongly affected by HIV, Rolle said she is "not sure" how effective Descovy will be in expanding the use of PrEP.
"For highly educated white men who have sex with men — yes, maybe. But for young black men who have sex with men," she paused, leaned back, and softly said, "No, I don't think so."
DISCOVER was funded by Gilead Sciences. Eron reports receiving consulting fees from Gilead Sciences, Janssen, Merck, and ViiV Healthcare. del Rio reports receiving consulting fees from ViiV Healthcare and InnaVirVax. Hare and Armstrong have disclosed no relevant financial relationships. Rolle reports having received funding from Gilead Sciences, Janssen, and ViiV Healthcare.
Conference on Retroviruses and Opportunistic Infections (CROI) 2019. Abstract OA O-10 104LB. Presented March 6, 2019.
Medscape Medical News © 2019
Cite this: 'Grappling' With the Value of Descovy for HIV PrEP - Medscape - Mar 07, 2019.