Randomized clinical trial on efficacy of fixed-dose efavirenz/tenofovir/emtricitabine on alternate days versus continuous treatment.

OBJECTIVE: Antiretrovirals with long half-lives, such as tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and efavirenz (EFV), are suitable for reduced frequency dosing, with potential for improved adherence and reduced toxicity and costs. The objective of this study was to investigate the noninferiority of the TDF/FTC/EFV fixed-dose combination on alternate-days versus standard regimen in virologically suppressed patients. DESIGN: A randomized-controlled open-label noninferiority trial enrolling HIV-1-infected patients treated for at least 6 months with TDF/FTC/EFV fixed-dose combination, virologically suppressed (<40 HIV-RNA copies/ml) with EFV plasma concentrations greater than 1000 ng/ml, were randomized to maintain TDF/FTC/EFV standard-of-care regimen (SOC, Arm A) or to switch to TDF/FTC/EFV on AlTernAte Days (ATAD, Arm B). METHODS: Primary end-point was the proportion of patients with less than 40 HIV-RNA copies/ml at week 48. RESULTS: One hundred and ninety-seven patients were randomized (98 in the SOC and 99 in the ATAD arm). One hundred and seventy-nine (90.3%) were men, median age 43.2 years, 133 (67.5%) MSM. CD4+ T-cell count at baseline was 706 cells/µl in SOC and 632 cells/µl in ATAD arm. At week 48, 95 (96.9%) patients in SOC and 93 (93.9%) in ATAD had a virological response (-3.0% overall risk difference, 95% CI: -8.86%/2.86%). Median change from baseline at week 48 in CD4+ T-cell count was 29.4 cells/µl (95% CI: 2.5/56.4) in SOC (P = 0.008) and 61.0 cells/µl (95% CI: 32.1/89.9) in ATAD (P < 0.001). Median change of EFV concentration at week 48 from baseline was -6.5 ng/ml (95% CI: -103/55) in SOC (P = 0.877) and -1124 ng/ml (95% CI: -1375/-928) in ATAD arm (P < 0.001). CONCLUSION: Despite a significant decrease of EFV exposure, TDF/FTC/EFV on ATAD was noninferior to SOC regimen through 48 weeks.

Development and validation of an HPLC-UV method for quantification of elvitegravir and two other new antiretrovirals, dolutegravir and rilpivirine, in the plasma of HIV-positive patients.

Therapeutic drug monitoring may be crucial in selected clinical conditions for the management of HIV infection. In recent years, new antiretrovirals have been introduced and in particular elvitegravir (EVG) is now recommended for first-line and simplification treatment as well as dolutegravir (DTG) and rilpivirine (RPV). The aim of this study was to develop and validate a high-performance liquid chromatography-ultraviolet (HPLC-UV) method for determining EVG and new antiretrovirals DTG and RPV in human plasma. Solid-phase extraction was applied to a 600 µL plasma sample. Chromatographic separation of the three drugs and internal standard was achieved with a gradient of acetonitrile and phosphate buffer on a C18 reverse-phase analytical column with a 20 min analytical run time. EVG and DTG were detected at 265 nm and RPV at 290 nm. Mean intra- and inter-day precisions were < 10%; the mean accuracy was <15%. Extraction recovery ranged between 105 and 82% for the drugs analyzed. Calibration curves were optimized according to the expected ranges of drug concentrations in patients; the coefficient of determination was >0.997 for all drugs. This method allows for monitoring EVG, DTG and RPV in the plasma of HIV-positive patients using HPLC-UV.