Gilead Sciences has begun a major trial to compare the efficacy of Descovy (emtricitabine/tenofovir alafenamide, or TAF) versus Truvada (tenofovir disoproxil fumarate, or TDF/emtricitabine) as pre-exposure prophylaxis (PrEP) against HIV.
In addition to determining how well Descovy protects against HIV compared with Truvada, the trial will compare the drugs’ effects on bone mineral density and kidney function, as well as other safety data.
The U.S. Food and Drug Administration (FDA) approved Descovy in April 2016 to be used in combination with other antiretrovirals (ARVs) to treat HIV. Research among HIV-positive people has shown that the drug is less toxic to the bones and kidneys than Truvada. The reason is that Descovy contains an updated version of the drug tenofovir, called TAF, while Truvada contains the older take on that drug, TDF. Both tablets also contain the drug emtricitabine.
The two major long-term potential side effects of Truvada as PrEP are modest declines in bone mineral density and kidney function. Research has found that both shifts are reversible after stopping Truvada as PrEP, although there is not yet data on whether such a reversal occurs following more than about a year of Truvada among HIV-negative people. Recent research has also raised the question of whether Truvada as PrEP may stunt bone growth among people in their teens and early twenties whose bones are still growing.
Truvada (tenofovir/emtricitabine), which was approved in 2004 for use in HIV treatment, was approved in 2012 as PrEP—to be taken daily as prevention against HIV among those who are at risk of contracting the virus.
Findings from a major study of Truvada as PrEP led researchers to estimate that it is more than 99 percent effective at preventing HIV when taken daily. No one in any of the major trials of PrEP among men who have sex with men (MSM) has contracted the virus while apparently taking Truvada four or more times a week. However, there has been one documented case of a Canadian man who contracted a rare, highly drug resistant strain of HIV while apparently adhering well to the daily PrEP regimen.
Following promising results from animal research, Gilead has begun planning a Phase III, randomized, double-blind trial comparing Descovy and Truvada’s efficacy in preventing HIV among an expected 5,000 transgender women and cisgender men who have sex with men who are at risk of contracting HIV.
The trial, called DISCOVER, will be conducted at numerous sites throughout the United States as well as in Canada and various Western European nations. Several U.S. sites have already started screening potential participants.
To be eligible, individuals must: be 18 years old or older; be HIV negative; report condomless anal sex with at least two partners in the past 12 weeks who are either HIV-positive or of an unknown HIV status; have been diagnosed with syphilis in the past 24 weeks or have been diagnosed with rectal gonorrhea or chlamydia in the past 24 weeks; have no known active or serious infections; have adequate kidney and liver function; have no evidence of viral hepatitis or acute hepatitis B virus (HBV) infection; have no evidence of or known history of hepatitis C virus (HCV) infection; have no evidence of osteoporosis or fractures related to bone fragility; and have no grade 3 or 4 protein or sugar in their urine that is unexplained or not manageable with treatment.
Gilead is also planning to conduct a trial of Descovy as PrEP among people with reduced kidney function.
The participants will be randomized to receive either Descovy or Truvada with instructions to take it daily. Neither the participants nor the trial investigators will know which medication the participants have received.
The participants will be followed for at least 96 weeks. Once all of them have been in the trial for at least that long, the investigators will unblind the study, revealing who was taking which tablet. At that time, the participants will be offered the opportunity to participate in an open-label extension phase of the trial, in which they will be offered unblinded Descovy.
Once everyone has been in the trial for at least 48 weeks and at least half of them have completed 96 weeks of follow-up, the researchers will determine how well each drug protected against HIV. Gilead estimates that this point will occur in February 2019 and that the study will reach its completion in September 2020.
In other words, Truvada will likely remain the only approved form of PrEP throughout the decade. Various other forms, including a long-term injectable that may be approved in 2020, are currently under investigation.
The Descovy vs. Truvada trial will also look at changes in indicators of kidney function and bone mineral density, both 48 weeks and 96 weeks into individuals’ participation in the trial. Additionally, the investigators will gather safety data about the rates of other adverse health events and the results of any other lab tests indicating potential medication-related toxicities.
Jim Pickett, director of prevention advocacy and gay men’s health at AIDS Foundation of Chicago has expressed concern that individuals may perceive this trial as a way to get free PrEP.
“Folks need to understand that the DISCOVER trial is not designed to expand access to Truvada as PrEP,” Pickett says, stressing the fact that science has already determined that Truvada is highly effective at preventing HIV while Descovy’s efficacy will remain unknown until this study produces results.
“No one in the study will know if they are getting Truvada or the investigational drug. People vulnerable to HIV who are being recruited into this study, and their allies, must understand this very important point.”
Indeed, there is the chance that Descovy will not be as effective as Truvada and that participants in the trial who receive Descovy may contract HIV whereas they would not have if they had been taking Truvada.
To read more about the clinical trial, click here. (Check back for updated information about how to participate.)
Update: A previous version of this article stated that Gilead will require that participants in the study not have taken Truvada as PrEP for 30 days prior to enrollment. Gilead recently eliminated this requirement.