Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials

Abstract

Background: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet regimen recommended for HIV-1 treatment. The safety and efficacy of B/F/TAF as initial therapy was established in two Phase 3 studies: 1489 (vs dolutegravir [DTG]/abacavir/lamivudine) and 1490 (vs DTG + F/TAF). After 144 weeks of randomized follow-up, an open-label extension evaluated B/F/TAF to 240 weeks.

Methods: Of 634 participants randomized to B/F/TAF, 519 completed the double-blinded treatment, and 506/634 (80%) chose the 96-week open-label B/F/TAF extension, which was completed by 444/506 (88%) participants. Efficacy was based on the secondary outcome of the proportion of participants with HIV-1 RNA <50 copies/mL at Week 240 by missing = excluded and missing = failure methods. All 634 participants who were randomized to B/F/TAF and received at least one dose of B/F/TAF were included in efficacy and safety analyses. (Study 1489: ClinicalTrials.govNCT02607930; EudraCT 2015-004024-54. Study 1490: ClinicalTrials.govNCT02607956; EudraCT 2015-003988-10).

Findings: Of those with available virologic data, 98.6% (95% CI [97.0%-99.5%], 426/432) maintained HIV-1 RNA <50 copies/mL at Week 240 (missing = excluded); when missing virologic data were considered as failure, 67.2% (95% CI [63.4%-70.8%], 426/634) maintained HIV-1 RNA <50 copies/mL. Mean (SD) change in CD4+ count from baseline was +338 (236.2) cells/μL. No treatment-emergent resistance to B/F/TAF was detected. Adverse events led to drug discontinuation in 1.6% (n = 10/634) of participants (n = 5 with events considered drug-related). No discontinuations were due to renal adverse events. Median (IQR) total cholesterol increased 21 (1,42) mg/dL from baseline; the change in total cholesterol:HDL was 0.1 (-0.5,0.6). Median (IQR) weight change from baseline was +6.1 kg (2.0, 11.7) at Week 240. In Study 1489, hip and spine bone mineral density mean percent changes from baseline were ≤0.6%.

Interpretation: Through 5 years of follow-up, B/F/TAF maintained high rates of virologic suppression with no treatment-emergent resistance and rare drug discontinuations due to adverse events. These results demonstrate the durability and safety of B/F/TAF in people with HIV.

Funding: Gilead Sciences.

Keywords: Antiretroviral therapy; Bone safety; Integrase strand transfer inhibitor; Long-term; Renal safety.

Fig. 1

Participant flow diagram. B/F/TAF, bictegravir/emtricitabine/tenofovir alafenamide; DTG/ABC/3TC, dolutegravir/abacavir/lamivudine.

Fig. 2

Virologic outcomes through 240 weeks (missing = excluded and missing = failure). Percent of participants with plasma HIV-1 RNA <50 copies/mL; n = participants with non-missing HIV-RNA value.

Fig. 3

Changes from baseline in estimated GFR_CG, bone mineral density, fasting lipids, and weight through 240 weeks. A. Median change in estimated glomerular filtration rate (eGFR_CG). Dotted line indicates median change at week 8. n = numbers of participants with non-missing eGFR_CG change values at the visit. Bars indicate interquartile range (IQR). B. Mean Percent Change in Bone Mineral Density (BMD). Measured by dual-energy x-ray absorptiometry in Study 1489 only; n = numbers for participants with non-missing % BMD change values at the visit. ∗151 participants with spine and 147 with hip bone mineral density (BMD) data from baseline through Week 240 with non-missing follow-up. Bars indicate 95% confidence interval (CI). C. Median Change in Fasting Lipids (mg/dL). n = number of participants with non-missing metabolic assessment values at the visit. ∗For all measures, n's were 619 at Week 0, 514 at Week 144, and 421 at Week 240. †Calculated as differences from Weeks 48–96, 96 to 144, 144 to 192, and 192 to 240. HDL, high-density lipoprotein; LDL, low-density lipoprotein; TC, total cholesterol; TG, triglycerides. Bars indicate interquartile range (IQR). D. Median Weight Change, kg/year. ∗Approximate date ranges. A. Median Change in Estimated Glomerular Filtration Rate (eGFR_CG). B. Mean Percent Change in Bone Mineral Density (BMD). C. Median Change in Fasting Lipids (mg/dL). D. Median Weight Change, kg/year.