The Food and Drug Administration (FDA) has approved daily Descovy (tenofovir alafenamide/emtricitabine) as a second pre-exposure prophylaxis (PrEP) option for most people.
Descovy is now approved for adults and adolescents weighing at least 35 kilograms, or about 77 pounds, to reduce the risk of contracting HIV via sex, with the exception of receptive vaginal sex. It should be taken once daily with or without food. Intermittent or on-demand use of Descovy before and after sex is not included in the approval. People wishing to use Descovy for PrEP should be tested to ensure than they are in fact HIV negative.
“PrEP drugs are highly effective when taken as indicated in the drug labeling and can prevent HIV infection,” Jeffrey Murray, MD, MPH, deputy director of the FDA’s Division of Antiviral Products said in a news release. “This approval provides more prevention options for certain patients at risk for acquiring HIV and helps further efforts by the FDA and the U.S. Department of Health and Human Services to facilitate the development of HIV treatment and prevention options to reduce new HIV infections.”
Gilead Sciences’ Descovy contains tenofovir alafenamide (TAF), an updated version of the tenofovir disoproxil fumarate (TDF) in the Truvada combination pill. Compared with TDF, TAF produces higher levels of the active drug in susceptible immune cells. This means TAF can be given at lower doses, leading to less drug exposure for the kidneys, bones and other organs.
Studies showed that TAF for PrEP has less effect on kidney function and bone loss biomarkers than TDF, although it is unclear whether this matters in terms of clinical outcomes like fractures. Conversely, TAF has a less favorable effect on blood lipid levels, which could have implications for cardiovascular risk.
The FDA approved Truvada for HIV prevention in 2012, an indication that includes adults and adolescents at risk for sexually acquired HIV regardless of sex, gender identity, sexual orientation or type of sexual activity.
The newly approved indication for Descovy PrEP is more limited. It includes cisgender (non-trans) men who have insertive anal or vaginal sex as well as for cisgender or transgender men and women who have receptive anal sex. It does not, however, include those who have receptive vaginal or frontal sex because there are insufficient data from clinical trials for such individuals.
A panel of independent experts voted at an August hearing to recommend FDA approval of Descovy PrEP for men who have sex with men and for trans women, but not for cisgender women. In the end, the agency decided to base the indication on the type of sexual activity rather than sexual orientation or gender identity.
The Phase III DISCOVER trial enrolled more than 5,300 men who have sex with men and a small number of trans women. Eligible participants were at high risk for HIV, having had recent condomless anal sex or been diagnosed with a sexually transmitted infection during the past six months. They were randomly assigned to take Descovy or Truvada once daily for two years.
As reported at the Conference on Retroviruses and Opportunistic Infections in March, both Descovy and Truvada proved highly effective for HIV prevention. After one to two years of follow-up, there were seven new HIV infections in the Descovy group and 15 in the Truvada group, yielding respective incidence rates of 0.16 and 0.34 per 100 cumulative years of follow-up. Among those who seroconverted, five were thought to have already had undetected HIV when they started the study, and 15 were found to have low tenofovir levels, indicating inconsistent use of PrEP.
Given the small number of infections in both groups, this difference was not statistically significant, meaning it could have been driven by chance. This led study investigators to conclude that Descovy is noninferior to, or just as effective as, Truvada for HIV prevention.
However, as reported at the recent International AIDS Society Conference on HIV Science in Mexico City, some researchers suggest that the lower seroconversion rate in the Descovy group might be attributable to the fact that TAF produces higher drug levels in immune cells, which are reached more quickly and persist longer as compared with TDF.
This extra “forgiveness” may be especially important for those using an on-demand, or 2-1-1, PrEP regimen taken before and after sex. In addition, prior studies have shown that tenofovir reaches lower levels and doesn’t last as long in vaginal and cervical tissue compared with rectal tissue, so Descovy may provide extra protection for cisgender women and potentially for trans women and men who have vaginal or frontal sex.
Because cisgender women were not included in DISCOVER, Gilead urged the FDA to extrapolate from pharmacokinetic data about how drugs are metabolized and distributed in the body. But for now, given the available clinical trial data, the FDA declined to include cisgender women and others who have receptive vaginal or frontal sex in the approved indication. Although most DISCOVER participants were cisgender men who have sex with men, the FDA reviewers felt comfortable extending the indication to men who have insertive vaginal sex.
Given the very low rate of HIV acquisition in both arms of the DISCOVER study—as well as the very high effectiveness of Truvada PrEP in clinical trials and real-world use—many experts think Descovy and Truvada are probably functionally equivalent for PrEP. And some advocates argue that the small difference won’t be worth the extra cost of Descovy once generic versions of Truvada become available starting next year.
Descovy and Truvada were both safe and well tolerated in the study. About 20% of participants in both groups reported drug-related side effects, most of which were mild or moderate. The most common side effect is nausea. Just 1% of Descovy recipients and 2% of Truvada recipients stopped taking PrEP because of adverse events. Biomarkers of kidney safety and bone mineral density favored Descovy over Truvada, which suggests Descovy may be a good option for people who have or are at risk for kidney and bone problems.
Descovy for HIV prevention must only be prescribed for people who are confirmed to be HIV negative immediately prior to starting PrEP. If a person already has HIV, they should take Descovy in combination with other drugs as part of a complete antiretroviral treatment regimen. Taking Descovy alone could lead to the development of drug resistance and limit future treatment options.
The tenofovir in Descovy is active against hepatitis B virus (HBV) as well as HIV, although the combination pill is not approved for hepatitis B treatment. For this reason, people who have both HIV and HBV should be monitored closely when they stop taking Descovy, as this could lead to worsening liver disease.
Gilead said in a press release that its medication assistance program for individuals with financial need and its co-pay coupon program for those with commercial insurance will be available for people who wish to use Descovy for PrEP.
“Descovy for PrEP provides a new HIV prevention option that matches Truvada’s high efficacy with statistically significant improvements in renal and bone safety, which can be an important consideration as people at risk increasingly use PrEP for longer periods of time,” said Gilead chairman and CEO Daniel O’Day.
[Editor’s note: In an October 5 letter to community members, Gilead indicated that the company has agreed with the FDA to conduct a study evaluating Descovy for PrEP in adult and adolescent cisgender women. “Community voices will be vital to provide input into key elements of the study, such as study design, site selection, recruitment and ongoing study management,” wrote Diana Brainard, Gilead’s Senior Vice President for HIV and Emerging Viral Infections.]
Click here for full prescribing information for Descovy.