A four-day-per-week regimen based on a nonnucleoside or a ritonavir-boosted protease inhibitor (PI) maintained viral loads below 50 copies/mL in 96 of 100 participants in a 48-week, multicenter, single-arm study. The four strategy failures included three virologic failures and one return to seven-day-per-week antiretroviral therapy (ART), according to the study presented at AIDS 2016.
Two previous trials, FOTO and BREATHER, found promising results with five-day-per-week antiretroviral regimens. French national HIV trials network (ANRS) investigators conducted a 48-week open-label, single-arm study to assess the efficacy and safety of ART for four consecutive days followed by three days without therapy.
The investigators defined failure as consecutive viral loads above 50 copies/mL two to four weeks apart or stopping the four-day strategy for more than 30 days. Participants were older than 18 years and taking a suppressive regimen including two nucleosides plus either a boosted PI or a nonnucleoside. Enrollees had not changed their regimen for four months and continued the same regimen in the trial. All had a viral load below 50 copies/mL for at least one year, and none had mutations conferring resistance to a drug in their current combination. They took their regimen from Monday through Thursday or from Tuesday through Friday and suspended treatment on the other days. Study visits were scheduled for day 0 and weeks 4, 8, 12, 16, 24, 32, 40, 48 and 51.
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The study included 100 participants with a median age of 47 years, 82 of them men and 65 men who have sex with men. Eighty-one participants were Caucasian and 10 were from Sub-Saharan Africa. Median duration of ART stood at 5.1 years and median HIV suppression measured 4.0 years. Participants had taken their current regimen for a median of 32.3 months. Seventy-one people were taking a nonnucleoside regimen and 29 a PI regimen.
Self-reported adherence to study medications was generally high. Twenty-one participants (21%) reported less than 80% adherence at one visit, as did four participants at two visits and only one participant at three visits. In a MEMS cap substudy involving 26 people, participants opened their pill bottles exactly four times a week during 44 of the 48 study weeks. Median concentrations of efavirenz (Sustiva, Stocrin) and etravirine (Intelence) stayed above efficacy cutoffs during off-ART periods, while concentrations of rilpivirine (Edurant), atazanavir (Reyataz), darunavir (Prezista) and lopinavir fell below efficacy cutoffs during the three-day drug holiday.
Median CD4 count rose from 708 to 748 cells/mm3 through 48 weeks, a moderate but statistically significant gain (P = .02). Median liver enzyme levels (AST, ALT and GGT) dropped significantly during the study, while glycemia rose from 5.0 to 5.2 mmol/L (P = .0282). Lipid levels did not change significantly. Seven severe adverse events arose but none were judged related to the study strategy.
Ninety-six of 100 study participants maintained a viral load below 50 copies/mL throughout the 48-week study. Three participants had a virologic failure; resistant virus did not emerge in any of these three people and all regained an undetectable viral load after they resumed seven-day-per-week therapy. One person returned to seven-day therapy at study week four and dropped out of the trial.
The ANRS team called for a comparative randomized trial with longer follow-up to "further inform the real efficacy and sustainability of this strategy." Adopting the strategy in clinical practice could pose risks not seen in a trial with follow-up visits every four to eight weeks.