Investigators are finding that a 4-days-a-week regimen of antiretroviral therapy (ART) may be as safe and effective as daily therapy in treating HIV, while keeping costs down and lowering risks of side effects.
Although antiretroviral therapy (ART) for HIV typically is prescribed as a once-a-day pill, scientists are increasingly recognizing that viral suppression can be achieved and maintained on a less frequent dosing schedule. Proponents of this so-called short cycle therapy cite cost-effectiveness, convenience, and fewer medication side effects as major benefits.
One trial investigating short cycle therapy took place from 2011 to 2013. It followed 199 people in 11 countries who were randomly assigned to either traditional daily therapy or 5-days-a-week therapy. After 48 weeks, the scientists conducting the study concluded that short cycle therapy was no less effective than daily therapy. Based on the success of that study, a group of French scientists decided to test an even shorter medication schedule of 4 days on and 3 consecutive days off.
The team recruited 100 HIV-positive adults, 82 of them were men, who had viral loads of less than 50 copies/mL. The average subject had been taking ART for a little more than 5 years and had CD4 counts in the normal range. Subjects were allowed to choose either Friday through Sunday or Saturday through Monday as their no-medication days, with blood tests and clinical exams given at regular intervals throughout the study’s 48-week duration.
The overall success rate in terms of viral suppression? 96%. “The study schedule was easy to recall for patients, with 3 days off on weekends, and restart of [ART] on Monday, or Tuesday in some patients,” Pierre de Truchis, MD, an infectious disease specialist at the Hôpital Raymond Poincaré in Garches, France, and the lead author of the study, told Contagion®. Three patients experienced virologic failure while following this 4-days-a-week schedule, leading them to return to a traditional daily medication regimen whereupon they again achieved viral suppression. “In 2 of the 3 failures, the assessment of drug concentrations led us to conclude that patients had stopped the treatment for more than 3 consecutive days,” Dr. de Truchis said. A fourth subject decided to go back to daily therapy after 1 month. The other 96 patients, however, achieved therapeutic success, with high self-reported adherence to the medication schedule.
A smaller 51-week follow-up study by the same team yielded similar results. In this study, which tracked compliance by electronically monitoring when subjects opened their medication bottles, the 29 subjects had compliance rates of at least 90% each week. Most reported being fully satisfied with the short cycle therapy at the 48-week mark (78.6%), compared with the 57.5% who claimed to be fully satisfied with 7-day-a-week therapy at the start of the study.
The study team was heartened by the absence of inflammatory activity in the subjects during the year that they were under observation, and are planning a longer study integrating more ART combinations to further explore the 4-day-a-week treatment plan as a safe, effective option for individuals with HIV. The relatively short duration of this trial, coupled with the lack of a control group, are 2 limitations that the team wants to address in the future.
As for the possibility of an even shorter cycle of medication, experts are not looking at that yet. “The efficacy of this therapy—4 days on, 3 days off—and previous concern about potential virological escape in patients with less than 4 of 7 days treatment in open-label reports...lead us not to go further and not to try 3 or 2 days a week,” Dr. de Truchis told Contagion®. “But we hope that we will be able to find benefit in tolerance in our ongoing randomized study.”
Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer- and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.