Once-a-Month PrEP on Its Way?

The experimental antiretroviral drug islatravir may be effective for HIV prevention when given once weekly and may be remain effective when used as infrequently as monthly, a new study indicates.

The study measured only how long the drug remains in the body, not whether it actually prevents HIV infection, but it still offers hope for a long-acting form of pre-exposure prophylaxis. PrEP users currently must take a pill daily.

Sharon Hillier, a professor at the University of Pittsburgh, presented the data Friday at the HIV Research for Prevention virtual conference, AIDSMap reports.

The U.S.-based phase IIa study used 250 volunteers to examine the level and persistence of islatravir in blood and tissue. Volunteers aged 18 to 65 at a low risk of HIV infection were divided into three groups. One hundred volunteers received an monthly oral dosage of 60 milligrams for a period of six months, 100 received a 120mg oral dosage for six months, and the remaining 50 received a placebo over the same period.

Drug levels were recorded immediately after dosing and each week during the first and sixth months of the study. For the second through the fifth months, only the trough levels, or those measured immediately before the next dose, were recorded.

The findings presented by Hillier were encouraging. Those taking the 60mg dose were shown to have 20 times the estimated efficacy threshold, while those who took the 120mg dosage had 40 to 50 times the efficacy threshold. The drug levels all fell within the range the researchers had expected across the test group with far smaller differences than predicted, and trough levels remained consistent as well.

In a minority of cases where data was available for up to 28 weeks, levels of islatravir were still four to five times the efficacy threshold a full eight weeks following the last dose. Hillier told the conference these results showed a once-monthly dose of the drug “provides enough forgiveness for people to be a couple of weeks late in taking their next dose.”

Some mild side effects were observed. One or more adverse reactions were reported by 53 percent of participants, with the most common being nausea, stomach pain, diarrhea, or other gastrointestinal complaints, or headaches.

So far, islatravir's effectiveness against HIV has been studied only in monkeys, but human trials are coming soon. Next up for islatravir are two human efficacy studies comparing monthly islatravir against daily dosages of Truvada (tenofovir disoproxil fumarate and emtricitabine) for women and either Truvada or Descovy (tenofovir alafenamide plus emtricitabine) for men. Truvada and Descovy are the only drugs so far approved for PrEP by the U.S. Food and Drug Administration. 

An abstract of Hillier's study can be found here.