Taking efavirenz/tenofovir/emtricitabine (Atripla) three days a week maintained an undetectable viral load for at least 24 weeks in people who were already virally suppressed for at least two years, according to a small, proof-of-concept study presented at ASM Microbe 2016 in Boston, Massachusetts.
The study, conducted in Spain, followed 61 individuals living with HIV (88.5% male and 11.5% female) who were stable on efavirenz/tenofovir/emtricitabine and had a viral load below 37 copies/mL for at least two years before study enrollment. All participants had a CD4 count above 350 at the start of the study, and none had previously documented virologic failure, though a single viral load blip between 50 and 200 copies/mL was allowed for study inclusion, according to lead study author Dr Esteban Martinez, consultant and associate professor of medicine Infectious Diseases Unit Hospital Clínic – IDIBAPS University of Barcelona.
Participants also had no evidence of resistance to efavirenz (Sustiva, Stocrin), tenofovir disoproxil fumarate (TDF, Viread) or emtricitabine (FTC, Emtriva). The volunteers were randomised to either continue taking efavirenz/tenofovir/emtricitabine once a day or reduce their regimen to three days a week (Mondays, Wednesdays and Fridays), about half in each group. Viral load was measured at baseline, 12 weeks and 24 weeks, but more thoroughly for the three-day group at 1, 2, 4, 6 and 8 weeks.
Most of the study cohort was male (89%); roughly two-thirds were Caucasian, while the rest of the volunteers were Hispanic; and three-quarters of the study participants were men who have sex with men. Mean age was roughly 48 years.
After 24 weeks, there were zero treatment failures in either study arm, and with 333 viral load tests in total, none were above 37 copies/mL, suggesting that taking antiretroviral therapy (at least in this case of efavirenz/tenofovir/emtricitabine) three days a week could be a feasible option to maintain undetectable viral loads.
Adherence was measured by standard questionnaire and pill counting, and the overall adherence rate was fine, according to Martinez. The researchers were worried the three-day group would not be able to adjust to the new schedule, and at times, patients missed one dose, but each of them managed to maintain the new schedule using smartphone calendars or other equivalents, he said.
Due to the outstanding results, the researchers asked the ethics committee to extend the study to three years, Martinez said. When asked about patient satisfaction, Martinez noted that all three-day patients were extremely satisfied and no one wanted to go back to once-daily dosing. In fact, participants in the control arm wanted to switch to three-day arm.
Data on participants' viral reservoirs were not included in the study poster presented at ASM Microbe 2016. However, Martinez noted that the reservoirs were measured using total and integrated DNA, and all patient reservoirs remained stable throughout the study.
When asked how applicable these results would be to current clinical care given the reduced use of efavirenz, Martinez stated that while the use of efavirenz is decreasing in first-world countries, it is still widely used in developing countries. At the very least, this confirms the potential for therapy doses to be farther apart than once a day, Martinez concluded.
Background: Antiretroviral drugs contained in single tablet Atripla® could allow for longer than once-daily (OD) dosing. We hypothesized that simplifying Atripla® OD to 3-day per week would be able to maintain viral suppression and less toxic. Methods: HIV+ adults on Atripla® OD, with HIV-1 RNA <37 copies/mL ≥2 years, CD4 >350/mm3 , and no prior virological failure or resistance mutations to study drugs were randomized to maintain their OD regimen or to reduce it to 3 days (Mondays, Wednesdays, and Fridays) a week (3W) (ClinicalTrials.gov: NCT01778413). Plasma HIV-1 RNA was measured at baseline, 12, and 24 weeks in both arms, and also at 1, 2, 4, 6, and 8 weeks in the 3W. Pittsburg Sleep Quality Index (PSQI), body mass index (BMI), bone mineral density (BMD), CD4 and CD8 cells, ultrasensitive HIV-1 RNA (1 copy/mL), plasma 25OH vitamin D and efavirenz levels, estimated flomerular filtration rate (CPK-EPI), fasting blood lipids and urinary proteins were measured at baseline and 24 weeks.
Results: Sixty-one patients included: 89% men, HIV-1 RNA <1 copy/mL 72%, median age 48 years, BMI 24 kg/m2, CD4 563/mm3, CD4/CD8 1.1, PSQI score 4, lumbar T-score -1.3, femur T-score -1.3, plasma 25OH vitamin D 18 ng/mL, plasma efavirenz 2.1 mg/L, CPK-EPI 101 mL/min, total chol 194 mg/dL, HDL chol 47 mg/dL, triglycerides 99 mg/dL, and urine protein/creatinine 75 mg/g, albumin/creatinine 4 mg/g, and beta-2-microglobulin 194 μg/g. All patients completed the study. Out of 333 plasma samples for HIV-1 RNA measurement during the study, none had ≥37 copies/mL. At 24 weeks, total chol and femur T-score significantly increased, while PSQI, plasma efavirenz, albumin/creatinine and beta-2-microglobulin in urine significantly decreased in the 3W arm relative to OD arm (table).
Conclusions: Three-day per week Atripla® in patients with sustained viral suppression is a feasible option that should be further confirmed in larger clinical trials.
E Martínez, J Rojas, JL Blanco, S Sanchez, A Marcos, M Lonca, B Torres, A Gonzalez-Cordon, A Romero, JM Gatell