People with undetectable viral load who switched from taking the Atripla single-tablet regimen (efavirenz/tenofovir/emtricitabine) every day to just every other weekday were able to maintain viral suppression for six months, and longer follow-up is planned, according to research presented last month at the ASM Microbe conference in Boston.
Fixed-dose combination pills have made HIV treatment more convenient, with several once-daily all-in-one regimens now available. Reducing the frequency of dosing even further would cost less, could reduce side-effects and could potentially promote better adherence; on the other hand, a non-daily regimen might make it harder to remember to take pills consistently.
Esteban Martínez and Jose Gatell of the University of Barcelona and colleagues conducted a proof-of-concept study to test whether simplifying treatment with Atripla to three days a week would be less toxic and able to maintain viral suppression. The component drugs in Atripla appear to allow for less frequent than once-daily dosing, they noted.
This analysis included 61 people with HIV who were currently taking once-daily Atripla with suppressed viral load (< 37 copies/ml) for at least two years, a CD4 count above 350 cells/mm3, no history of virological failure, and no known resistance to efavirenz, tenofovir disoproxil fumarate or emtricitabine.
Most participants were white men, the median age was about 48 years, the median CD4 count was approximately 560 cells/mm3 and most had undetectable HIV RNA using an ultrasensitive single-copy assay.
Study participants were randomly assigned to either stay on their once-daily Atripla regimen or reduce it to three days a week – on Mondays, Wednesdays and Fridays – for 24 weeks. Plasma viral load was measured at baseline, 12 and 24 weeks in both arms, and also at 1, 2, 4, 6 and 8 weeks in the thrice-weekly arm.
The researchers also looked at measures of tolerability including sleep quality, as efavirenz can cause insomnia and unusual dreams, and bone mineral density and kidney biomarkers, as tenofovir can cause bone loss and kidney function impairment.
Treatment was well tolerated and all participants completed the study. Adherence was good, as assessed by patient questionnaires and pill counts. As expected, efavirenz blood levels fell to lower levels between doses in the three-times-weekly arm compared to the once-daily arm.
No participants in either arm experienced virological failure over the 24 weeks of the study. Of the more than 300 plasma samples collected for HIV RNA measurement, none showed a viral load > 37 copies/ml. Participants in both the thrice-weekly and once-daily arms also maintained undetectable viral load using a single-copy assay.
At 24 weeks, Pittsburgh Sleep Quality Index scores improved among people taking Atripla less often, according to the study abstract.
Femur (thigh bone) bone density scores increased slightly in the three-times-weekly arm, while lumbar spine density did not change. Kidney biomarkers also showed improvement in the thrice-weekly arm. However, total cholesterol levels rose in the three-times-weekly arm; tenofovir is known to raise cholesterol, and this effect was smaller with less frequent dosing.
"Three-day per week Atripla in patients with sustained viral suppression is a feasible option that should be further confirmed in larger clinical trials," the researchers concluded.
Martínez said participants in the thrice-weekly arm reported that they were highly satisfied with the new regimen and did not want to return to daily dosing. The team now plans to extend the study through three years to see if less frequent Atripla can be used as a long-term maintenance regimen.
Martínez E et al. Three-day per week atripla in patients with sustained viral suppression. ASM Microbe, 2016. Abstract PW-029. View abstract.