George Froehle, PA, a primary care clinician at CentraCare in rural St. Cloud, Minnesota, has been prescribing the HIV prevention pill tenofovir disoproxil fumarate plus emtracitabine (TDF/FTC) since it was marketed by the brand name Truvada and the US Food and Drug Administration approved it in 2012. But recently, he’s been having conversations with patients about the new HIV prevention pill, tenofovir alafenamide plus emtracitabine (TAF/FTC, Descovy) as well.
“They may have a friend who has heard that Descovy is newer and safer,” Froehle said. But that’s not necessarily the case, at least according to lab values. A recent study in the journal Open Forum Infectious Diseases suggests that only between 1 in 10 and 1 in 3 switches to the new formulation of HIV pre-exposure prophylaxis (PrEP) are indicated by lab work — and that nearly half of people receiving a prescription for the new version had lab results actually contraindicating the switch.
This, combined with the lower cost of generic Truvada and the steep cost of Descovy, led study co-author and HIV PrEP prescriber Douglas Krakower, MD, and colleagues to suggest that the generic version should be standard of care for all people on PrEP unless otherwise indicated.
This just “makes good sense,” Krakower, assistant professor of medicine at Harvard Medical School, Boston, told Medscape Medical News.
“It’s important to ultimately allow for patients and providers to have access to all of the PrEP options so they can choose the best option for each person,” he said. “But our data suggest that strategies to optimize the cost-effectiveness of PrEP prescribing, such as formulary interventions and education for patients and providers, could be beneficial — as long as there is an easy mechanism for patients and providers to override restrictions when there are clinical indications.”
Current PrEP guidelines from the Centers for Disease Control and Prevention don’t list a first-line or second-line treatment for PrEP. But recent guidance issued to insurance companies by the Biden administration specifically grants insurers permission to employ stepped formularies and cost sharing.
“Since the branded version of PrEP is not specified in the [US Preventive Services Task Force] recommendation, plans and issuers may cover a generic version of PrEP without cost sharing and impose cost sharing on an equivalent branded version,” the rule, issued July 19, states. “However, plans and insurers must accommodate any individual for whom a particular PrEP medication (generic or brand name) would be medically inappropriate, as determined by the individual’s health care provider, by having a mechanism for waiving the otherwise applicable cost-sharing for the brand or nonpreferred brand version.”
Both drugs have been found to be 99% effective in stopping HIV acquisition in people at risk for it. Descovy is approved specifically for gay and bisexual men, transgender women, and anyone having anal sex. Ongoing studies are looking at the effectiveness of Descovy in people having vaginal sex. Generic Truvada has been approved for all people.
The Biomarkers of Switching
To be clear, both medicines are exceedingly safe, said lead author and epidemiologist Julia Marcus, PhD, MPH, associate professor at Harvard Medical School. Side effects have been mild and include nausea and diarrhea in the first month. What lab work tells clinicians is the potential for physiologic changes, but those changes don’t necessarily translate to clinical events.
“When I say harmful, I mean potentially harmful,” she said in an interview with Medscape. “It’s really based on these incremental changes that maybe, in the long run, could be harmful.”
But she added that there are two types of damage from medicines: “There’s potential physiological damage, but there’s also potential financial damage.” While generic Truvada has a list price as low as $30 a bottle, Descovy has a list price of up to $2000 a month. And the push for PrEP is growing. Recently, the head of the Division of HIV/AIDS at the National Institute of Allergy and Infectious Diseases (NIAID) urged providers to get all their “HIV-negative, at-risk patients on PrEP tomorrow,” in light of the latest HIV vaccine failure.
So Marcus and team looked at data from the 2892 people who started taking PrEP in the year before the FDA approved Descovy in October 2019. Participants accessed PrEP through Fenway Health, a Boston-area health clinic serving a largely gay, lesbian, bisexual, transgender, and otherwise queer population, and the largest PrEP prescriber in New England. They then tracked which participants switched to Descovy and correlated the switches to lab work and CDC guidance for PrEP.
What they found was that just 11.9% of participants, or 343 people, switched to the newer formulation. That’s lower than the 27.2% who switched in nationally available data, which were released at a recent HIV conference. But when Krakower and colleagues looked at whether their PrEP prescriptions were appropriate based on the patients’ lab work, the findings were mixed.
On the one hand, they showed that 24 of those 343 people who switched to Descovy had creatinine clearance levels or bone mineral density measurements low enough to make the switch a good option. But that’s just 7% of all people who switched. They then ran a secondary model, in which they broadened the criteria for a switch from strictly those lab values to conditions that might indicate borderline kidney function, which could eventually lead to kidney damage. These included diagnoses of hypertension or diabetes, or borderline creatinine levels between 60 and 70 mL/minute.
“Even when we defined clinical indications as generously as we could, we still saw that only a minority had clinical indications for switching,” said “Most of the switching to TAF/FTC was potentially unnecessary, and some of it may have been harmful for people who had cardiovascular risk factors.”
That’s because although Descovy doesn’t affect renal and bone mineral markers, it does affect cholesterol levels and weight. Aftermarket and FDA data revealed a small but noticeable increase in statin use among people taking the new brand-name PrEP pill. When Marcus and colleagues looked for those biomarkers — total cholesterol >200, BMI of 30 or more, LDL cholesterol of >160 or HDL cholesterol of <40 — 14% of switches fit the criteria for contraindications for Descovy. That’s 10 times the rate of potential harm in switching as there was for those who stayed on the generic Truvada and would have been better served on Descovy. That came in at just 1.4%.
“There may be many reasons why patients or providers might choose to switch that we couldn’t document in our study,” she said. For instance, the newer formulation, Descovy, is a significantly smaller pill than the generic is. Or the perception of novelty might drive some switches.
“But I think we need qualitative work to understand how these decisions are being made,” she told Medscape. “It will be important to follow these patients to see what happens in terms of clinical outcomes.”
For his part, PrEP prescriber Froehle found the study intriguing. It reflects his own thinking around the value of the newer formulation. He also prescribes for people living with HIV. For them, the benefit of the new formulation of tenofovir present in Descovy has clear clinical relevance. After all, people living with HIV can be on their drug regimens for decades.
But people on PrEP aren’t likely to be on the pills as long, and so the real benefit of the newer, more expensive formulation is less clear. And he added that he’s already getting “pushback” from some insurance companies on the name-brand version, with companies asking for proof via lab values that a person has a history of kidney impairment or bone mineral density loss.
“It doesn’t happen a ton,” he said. “But it’s starting to happen, and normally it kind of builds from there.”
So when a patient comes in and asks specifically for Descovy, he usually will talk to them about it.
“If it’s what the patient wants and insurance covers it and it’s not unsafe for them to be on it, there might not be a reason to not prescribe Descovy,” said Froehle, who served as a sub-principal investigator for the DISCOVER clinical trial that showed the new PrEP was as effective as Truvada. “But now with Truvada being generic, we will talk about Truvada as being something we start up front because it may have a lower cost and it’s cheaper to the system. Then we can always switch to Descovy as needed.”
Open Forum Infect Dis. Published online August 5, 2021. Full text
This study was funded by the National Institute of Allergy and Infectious Diseases.
Marcus reports receiving fees from Kaiser Permanente Northern California on a research grant from Gilead Sciences. Krakower reports having conducted research that was funded by Gilead Sciences and Merck, as well as honoraria for medical education content and presentations for Medscape Medical News, MED-IQ, and DKBMed and royalties from work conducted by UpToDate. Froehle reports receiving fees from Gilead Sciences in connection with a Gilead advisory board.
Heather Boerner is a science journalist based in Pittsburgh, PA. Her book, Positively Negative: Love, Pregnancy, and Science’s Surprising Victory Over HIV, came out in 2014.