AMSTERDAM – Episodic, “on-demand” pre-exposure prophylaxis to prevent transmission of HIV was as effective as daily pre-exposure prophylaxis in a prospective, real-world study of more than 1,100 men who have sex with men in the Paris region.
Mitchel L. Zoler/MDedge News
Dr. Jean-Michel Molina
The results showed very similar performance and complete prevention of new HIV infections in both groups, data that “strengthen the case for on-demand prophylaxis as an alternative to daily PrEP [pre-exposure prophylaxis],” Jean-Michel Molina, MD, said at the 22nd International AIDS Conference.
The evidence for efficacy of on-demand PrEP, used starting a day before through a day after unprotected sex by a man uninfected by HIV, to prevent potential infection “is now good enough for clinicians to counsel people that it is equally effective as daily PrEP and the person can decide” which regimen to use, he said in an interview. “In the future, we’ll use both strategies. We want to make PrEP easy for people to use. We want alternatives so that more people use PrEP, ” said Dr. Molina, professor of infectious diseases at the University of Paris and head of infectious diseases at Saint-Louis Hospital in Paris.
However the study focused on men who have sex with men (MSM) and so the efficacy of on-demand PrEP is not proven for preventing HIV infection during heterosexual sex, including protecting women, Dr. Molina cautioned.
The on-demand PrEP regimen tested by Dr. Molina and his associates uses the same combination of 300 mg tenofovir (Viread) and 200 mg emtricitabine (Emtriva) – formulated into a single pill and marketed as Truvada – as used for daily PrEP.
For on-demand use patients take two of these pills 2-24 hours prior to their anticipated sexual activity and then 1 pill every 24 hours until the sexual activity stops, with a final pill 24 hours following the last sex event. This translates into an ideal regimen of at least 4 pills total.
The researchers first documented the efficacy of on-demand PrEP in a placebo-controlled study with 400 randomized people that showed the on-demand regimen reduced the rate of new HIV infection by 86%, compared with placebo, among MSM who had unprotected sex (N Engl J Med. 2015 Dec 3;373[23]:2237-46). They designed the current, open-label study, ANRS-PREVENIR (Prevention of HIV in Île-de-France), to further examine the efficacy of and adherence to an on-demand PrEP regimen in a real-world setting and to compare it with daily PrEP.
The study began in May 2017, with a goal of enrolling 3,000 HIV-negative MSM. As of early July 2018, the study had enrolled 1,628 people including 1,102 who had been followed for at least 3 months and for an average of 7 months, including 124 followed for at least 1 year. Participants had a choice of using PrEP in either an on-demand or daily regimen and were allowed to switch from one regimen to the other. At enrollment, 55% opted for the on-demand regimen, and during subsequent months the fraction of participants using an on-demand regimen remained at about half. Based on self-reported use of the regimen, 96% of the men who had opted for on-demand PrEP used it “correctly,” defined as taking at least one pill within 24 hours of their sex event and at least one pill within 24 hours after the event, a rate that was identical to the “correct” usage by participants who opted for daily PrEP. The only substantial difference in PrEP use between the two subgroups was that 19% of men in the on-demand group did not use PrEP prior to at least one sex event, compared with 2% of men in the daily subgroup.
“We need to better understand” why so many participants in the on-demand group failed to use PrEP, admitted Dr. Molina. He speculated that these failures to use PrEP occurred because participants had sex with partners whom they knew were not infected with HIV.
During follow-up, the researchers identified no one who became HIV infected during 949 person-years of follow-up, a level of protection from PrEP that Dr. Molina called “remarkable.” Based on the epidemiology of HIV in the Paris region he estimated that use of PrEP by the participants in the study had prevented what might have otherwise been 85 new HIV infections. During follow-up, participants completely stopped using either daily or on-demand PrEP at a rate of 1.5 discontinuations per 100 person-years.
The incidence of adverse events was similar in the two arms of the study, with no discontinuations because of adverse events, and a 4-5 per 100 person-years incidence of grade 3 or 4 adverse events and an incidence of 2 per 100 person-years of grade 3 or 4 laboratory abnormalities. “The drugs are very well tolerated,” Dr. Molina noted, and a potential reduction in adverse events is not a reason for someone to choose on-demand PrEP instead of daily use. The primary difference is a potentially smaller pill burden: People using on-demand PrEP take on average about half the number of pills as someone on daily PrEP, which could lower the cost of prophylaxis in countries or settings where the person on PrEP has financial responsibility for the drugs. This was not an issue in the current study as the pills are available to people at no charge under the French health coverage system, Dr. Molina noted.
“On-demand PrEP is a viable option. For some people on-demand makes sense,” commented Patrick Sullivan, PhD, a professor of epidemiology at Emory University in Atlanta. It can potentially reduce drug costs, an issue for many Americans, Dr. Sullivan noted in an interview. So far, however, no reported studies have documented the efficacy of on-demand PrEP in a U.S. population, he said.
On-demand PrEP has received endorsement for use by selected people at high risk for HIV infection by public health authorities in the European Union, the United Kingdom, France, Canada, and Australia, Dr. Molina said, and in late July this strategy also received endorsement in revised HIV treatment and prevention recommendations issued by the International Antiviral Society–USA (JAMA. 2018 July 24/31;320[4]:379-96).
ANRS-PREVENIR received no commercial funding. Dr. Molina has been an advisor to Gilead, Merck, Teva, and Viiv and has received research fundings from Gilead.
SOURCE: Molina J-M et al. AIDS 2018, Abstract 13278.