For seven years, there was only one drug approved by the U.S. Food and Drug Administration (FDA) to prevent HIV infection: Truvada (emtricitabine/tenofovir disoproxil fumarate). Last month, the FDA approved a second drug, Descovy (emtricitabine/tenofovir alafenamide), to prevent HIV in people having anal sex, though it wasn't tested -- and therefore was not approved -- to prevent HIV during instances of vaginal sex. Both drugs had been previously approved for use in treating HIV-positive people. The newer tenofovir alafenamide (TAF) component in Descovy makes it more effective at entering cells, so a much smaller dose is needed than with tenofovir disoproxil fumarate (TDF, sold as Viread), which is used in Truvada. And in theory, a lower dose lessens the chance of toxicities.
But is Descovy/TAF actually better, and should clinicians be shifting their patients off Truvada en masse? The DISCOVER trial proved TAF is non-inferior to Truvada/TDF, meaning, legally, the company could not claim Descovy/TAF is better for use as pre-exposure prophylaxis (PrEP). But you wouldn't know Descovy was simply non-inferior by listening to the drug maker, Gilead Sciences. The company has been urging doctors and patients to switch to Descovy, claiming it's safer than Truvada but not really explaining how it's safer, or for what purpose -- treatment or prevention.
The Pros and Cons of Descovy and Truvada: It's Complicated
In a 2018 study published in the Journal of Virus Eradication, Andrew Hill, M.D., Ph.D., from the University of Liverpool, and his coauthors concluded that there were differences in bone mineral density between unboosted TAF and unboosted TDF but said the "clinical significance of these differences is unclear."
The DISCOVER trial tested unboosted Descovy/TAF for use as PrEP on 5,313 men and 74 transgender women who have sex with men, but not on cisgender women or transgender men. Eighty-four percent of the participants were white. While the trial showed minor improvements in bone density and renal health indicators in Descovy/TAF compared to Truvada/TDF, TAF showed a higher indication of obesity and cardiovascular issues than TDF, especially for communities of color and women, populations that were underrepresented in studies. And that's something that needs further study, according to James Krellenstein, co-founder of the PrEP4All Collaboration.
"Fifteen percent of the subjects in the DISCOVER trial were black, but 46% of new HIV diagnoses in the U.S. are black," Krellenstein says. "It's possible that Gilead is underestimating the possible weight gain and cardiovascular problems among subjects [on Descovy] because they didn't include enough black people."
Jeremiah Johnson, HIV program director at Treatment Action Group, and other advocates point out that one big problem with choosing one drug regimen over another is the conflation of treatment and PrEP use in Gilead's statements, and in the minds of clinicians and patients. Both drugs work equally well in both preventing HIV infection and treating HIV. Truvada has shown some serious health complications, but for HIV-positive people using it for treatment, not for PrEP.
For use as treatment in HIV-positive patients, Descovy/TAF, when combined with a boosting agent, has also shown some negative health biomarkers. Last month, a study found "significant increases in weight, BMI, total cholesterol, LDL, HDL, and ASCVD [atherosclerotic cardiovascular disease] risk score in the year after switching from TDF to TAF" for use in treating HIV. Also last month, a Gilead-sponsored study of antiretroviral therapy looked at eight large clinical trials and found that TAF was associated with a greater than 10% weight gain in some patients, while TDF, abacavir, and AZT were not. All of these side effects were more pronounced in cisgender women. But, remember, Gilead did not study Descovy for use as PrEP in cisgender women.
The FDA has not approved Descovy/TAF for 2-1-1, or intermittent, PrEP use. And as for vaginal sex, 2-1-1 wasn't tested either.
But for PrEP, if both drugs work equally well and cost the same -- though Gilead has tipped the scales to Descovy by giving favorable rebates for medical centers participating in the 340B drug discount program -- what's wrong with a clinic or a doctor shifting all patients to Descovy? Krellenstein says it's just not that simple, especially given that Descovy has not been tested on a population that mirrors the people most at risk for HIV. "Patients need to have a risk-benefit conversation with their clinicians," he says, and not automatically accept that Descovy will be better.
As always, you should have a conversation with your doctor or clinician before making the choice.
Is Gilead Misleading Doctors and Patients?
Class-action suits claiming Truvada led to bone density and kidney failure -- you may have seen one of the many lawsuit ads on your social media feeds -- are also leading patients, clinicians, and clinics providing access to PrEP to move wholesale to Descovy/TAF. And Gilead isn't pushing back on the perception that this newer, tweaked -- and non-inferior -- drug is safer for every indication. That's a problem, advocates say, because people wanting PrEP, as well as some wanting treatment, are being pushed out of Truvada onto Descovy, when they might not need to be.
In an email statement, a Gilead spokesman said the company "clearly stated that the efficacy of Descovy is non-inferior to Truvada for the prevention of HIV."
But in a statement coinciding with the FDA's approval of Descovy for PrEP last month, Gilead CEO Daniel O'Day wrote that Descovy "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."
HIV and PrEP advocates are calling foul, saying the improvements in renal and bone safety are not significant -- not for PrEP, anyway -- and that the company is misrepresenting studies in order to switch over patients to Descovy/TAF before a generic version of Truvada/TDF is available sometime next year. And they point to recent studies showing the possibility of troubling side effects with Descovy/TAF for use as PrEP.
"We're worried that, because doctors and clinicians have high caseloads, it's sometimes difficult to keep up with the latest health news," Johnson of Treatment Action Group tells TheBody. "And a company with a huge amount of resources can influence health care providers who don't have time to evaluate the pros and cons." Johnson adds that he believes Gilead is "making sure we're not having an authentic, evidence-based conversation" on the differences between the two pills.