Efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-based three-drug regimens in people with HIV with varying adherence to antiretroviral therapy

Abstract

Objective: Five Phase 3 bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) clinical studies demonstrated that the efficacy of B/F/TAF was non-inferior to dolutegravir (DTG) + 2 NRTIs. We retrospectively assessed drug adherence and effect on virologic outcomes.

Methods: Studies (NCT02607930, NCT02607956, NCT03547908, NCT02603120 and NCT03110380) were double-blind, placebo-controlled and enrolled treatment-naïve or virologically suppressed adults. Adherence was calculated by pill count from returned pill bottles; virologic outcome was assessed by last on-treatment HIV-1 RNA.

Results: Altogether, 2622 participants (B/F/TAF: n = 1306; DTG + 2 NRTIs: n = 1316) were categorized as having high (≥95%), intermediate (≥85% to <95%) or low (<85%) adherence. Through Week 48, low adherence was observed in 46 (3.5%) participants in the B/F/TAF group (78% median adherence) and 69 (5.2%) in the DTG + 2 NRTI group (80% median adherence). Overall, 1287 (98.5%) participants in the B/F/TAF group and 1292 (98.2%) in the DTG + 2 NRTI group had virologic suppression (VS; HIV-1 RNA < 50 copies/mL) through Week 48. VS in participants with low adherence versus high or intermediate adherence was similar in the B/F/TAF group, but lower in the DTG + 2 NRTI group (P ≤ 0.002). Similar results were observed at Weeks 96 and 144. Two participants (<95% adherence) in the DTG + 2 NRTI group receiving DTG and abacavir/lamivudine developed M184V; there was no treatment-emergent resistance to B/F/TAF.

Conclusions: Participants with suboptimal (<85%) adherence to B/F/TAF maintained high levels of VS, whereas suboptimal DTG + 2 NRTI adherence was associated with lower VS.

Figure 1.

Virologic suppression (HIV-1 RNA < 50 copies/mL) at last visit through Weeks 48, 96 and 144 by treatment group and adherence category. Proportions of participants with virologic suppression were compared within or between treatment groups, with P-values determined by Cochran–Mantel–Haenszel test, adjusted by participant population type. At Week 48, studies GS-US-380-1489, GS-US-380-1490, GS-US-380-4458, GS-US-380-1844 and GS-US-380-4030 were included; DTG + 2 NRTI regimens were DTG/ABC/3TC (n = 595), DTG + F/TAF (n = 600) or DTG + F/TDF (n = 121) (a, d). At Week 96, studies GS-US-380-1489, GS-US-380-1490 and GS-US-380-4458 were included; DTG + 2 NRTI regimens were DTG/ABC/3TC (n = 314), DTG + F/TAF (n = 323) or DTG + F/TDF (n = 121) (b, d). At Week 144, studies GS-US-380-1489 and GS-US-380-1490 were included; DTG + 2 NRTI regimens were DTG/ABC/3TC (n = 314) or DTG + F/TAF (n = 323) (c, d). 3TC, lamivudine; ABC, abacavir; B/F/TAF, bictegravir/emtricitabine/tenofovir alafenamide; DTG, dolutegravir; F, emtricitabine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. *P < 0.05, **P < 0.0001. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 2.

Virologic outcomes at Weeks 48, 96 and 144 (HIV-1 RNA cut-off at 50 copies/mL defined by Snapshot algorithm) by treatment group and adherence category. At Week 48, studies GS-US-380-1489, GS-US-380-1490, GS-US-380-4458, GS-US-380-1844 and GS-US-380-4030 were included; DTG + 2 NRTI regimens were DTG/ABC/3TC (n = 595), DTG + F/TAF (n = 600) or DTG + F/TDF (n = 121); DTG + 2 NRTI differences (95% CI) in HIV-1 RNA ≥50 copies/mL were −9.1% (−19.4% to −3.2%) for high versus low and −8.4% (−18.3% to −1.6%) for intermediate versus low adherence (a, d). At Week 96, studies GS-US-380-1489, GS-US-380-1490 and GS-US-380-4458 were included; DTG + 2 NRTI regimens were DTG/ABC/3TC (n = 314), DTG + F/TAF (n = 323) or DTG + F/TDF (n = 121); DTG + 2 NRTI differences (95% CI) in HIV-1 RNA ≥50 copies/mL were −10.2% (−23.5% to −2.3% for high versus low and −8.7% (−21.5% to −0.1%) for intermediate versus low adherence (b, d). At Week 144, studies GS-US-380-1489 and GS-US-380-1490 were included; DTG + 2 NRTI regimens were DTG/ABC/3TC (n = 314) or DTG + F/TAF (n = 323); DTG + 2 NRTI differences (95% CI) in HIV-1 RNA ≥50 copies/mL were −14.8% (−29.4% to −5.9%) for high versus low and −11.6% (−26.0% to −1.4%) for intermediate versus low adherence (c, d). Proportions of participants with low adherence who had HIV-1 RNA  ≥ 50 copies/mL were compared within or between treatment groups, with P-values determined by Cochran–Mantel–Haenszel test, adjusted by participant population type (d). 3TC, lamivudine; ABC, abacavir; B/F/TAF, bictegravir/emtricitabine/tenofovir alafenamide; DTG, dolutegravir; F, emtricitabine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. *P < 0.05, **P < 0.0001. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 3.

Virologic suppression (HIV-1 RNA < 50 copies/mL) at Weeks 48, 96 and 144 on treatment by missing = excluded imputation by treatment group and adherence category. All treated participants who had non-missing HIV-1 RNA data at Weeks 48 (a), 96 (b) and 144 (c) and evaluable adherence data were eligible. Proportions of participants with virologic suppression at were compared within treatment groups, with P-values determined using Cochran–Mantel–Haenszel test, adjusted by participant population type. 3TC, lamivudine; ABC, abacavir; B/F/TAF, bictegravir/emtricitabine/tenofovir alafenamide; DTG, dolutegravir; F, emtricitabine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. *P < 0.05. **P<0.0001. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.