Switching to Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Virologically Suppressed Adults With Human Immunodeficiency Virus.
Bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) is guideline-recommended treatment for human immunodeficiency virus type 1 (HIV-1). We evaluated whether people receiving dolutegravir (DTG) plus F/TAF or F/TDF (tenofovir disoproxil fumarate) with viral suppression can switch to B/F/TAF without compromising safety or efficacy, regardless of preexisting nucleoside reverse transcriptase inhibitor (NRTI) resistance.
In this multicenter, randomized, double-blinded, active-controlled, noninferiority trial, we enrolled adults who were virologically suppressed for ≥6 months before screening (with documented/suspected NRTI resistance) or ≥3 months before screening (with no documented/suspected NRTI resistance) on DTG plus either F/TDF or F/TAF. We randomly assigned (1:1) participants to switch to B/F/TAF or DTG + F/TAF once daily for 48 weeks, each with matching placebo. The primary endpoint was proportion of participants with plasma HIV-1 RNA ≥50 copies/mL at week 48 (snapshot algorithm); the prespecified noninferiority margin was 4%.
Five hundred sixty-seven adults were randomized; 565 were treated (284 B/F/TAF, 281 DTG + F/TAF). At week 48, B/F/TAF was noninferior to DTG + F/TAF, as 0.4% (1/284) vs 1.1% (3/281) had HIV-1 RNA ≥50 copies/mL (difference, -0.7% [95.001% confidence interval {CI}, -2.8% to 1.0%]). There were no significant differences in efficacy among participants with suspected or confirmed prior NRTI resistance (n = 138). No participant had treatment-emergent drug resistance. Median weight change from baseline at week 48 was +1.3 kg (B/F/TAF) vs +1.1 kg (DTG + F/TAF) (P = .46). Weight change differed by baseline NRTIs (+2.2 kg [F/TDF] and +0.6 kg [F/TAF], P < .001), with no differences between B/F/TAF and DTG + F/TAF.
The single-tablet regimen B/F/TAF is a safe, effective option for people virologically suppressed on DTG plus either F/TDF or F/TAF, including in individuals with preexisting resistance to NRTIs.
NCT03110380.
Sax PE
，Rockstroh JK
，Luetkemeyer AF
，Yazdanpanah Y
，Ward D
，Trottier B
，Rieger A
，Liu H
，Acosta R
，Collins SE
，Brainard DM
，Martin H
，GS-US-380–4030 Investigators
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Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study.
With the highest rates of HIV/AIDS in the United States, Black Americans are still underrepresented in HIV medical research.
BRAAVE (NCT03631732) is a randomized, phase 3b, multicenter, open-label US study.
Adults identifying as Black or African American and virologically suppressed on 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus third agent were randomized (2:1) to switch to open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) once daily or stay on baseline regimen (SBR) for 24 weeks, after which SBR had delayed switch to B/F/TAF. Resistance to non-NRTIs, protease inhibitors, and/or NRTIs was permitted; integrase strand transfer inhibitor resistance was exclusionary. Primary endpoint was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 24 (snapshot algorithm; noninferiority margin of 6%).
Of 558 screened, 495 were randomized/treated (B/F/TAF n = 330; SBR n = 165). Overall, 32% were ciswomen, 2% transwomen, and 10% had an M184V/I mutation. At week 24, 0.6% on B/F/TAF vs 1.8% on SBR had HIV-1 RNA ≥50 copies/mL (difference -1.2%; 95% confidence interval -4.8% to 0.9%), demonstrating noninferiority of B/F/TAF vs SBR. Proportions with HIV-1 RNA <50 copies/mL at week 24 were 96% B/F/TAF and 95% SBR and remained high at week 48. No participant had treatment-emergent resistance to study drug. Treatments were well tolerated. Study drug-related adverse events, mostly grade 1, occurred in 10% of participants on B/F/TAF through week 48 and led to discontinuation in 9 participants through week 48.
For Black Americans with HIV, switching to B/F/TAF was noninferior to continuing a variety of regimens, including those with pre-existing NRTI mutations.
Hagins D
，Kumar P
，Saag M
，Wurapa AK
，Brar I
，Berger D
，Osiyemi O
，Hileman CO
，Ramgopal MN
，McDonald C
，Blair C
，Andreatta K
，Collins SE
，Brainard DM
，Martin H
，BRAAVE2020 Investigators
... -
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Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phas
Bictegravir, co-formulated with emtricitabine and tenofovir alafenamide, has shown good efficacy and tolerability, and similar bone, renal, and lipid profiles to dolutegravir, abacavir, and lamivudine, in treatment-naive adults with HIV-1 infection, without development of treatment-emergent resistance. Here, we report 48-week results of a phase 3 study investigating switching to bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir, abacavir, and lamivudine in virologically suppressed adults with HIV-1 infection.
In this multicentre, randomised, double-blind, active-controlled, non-inferiority, phase 3 trial, HIV-1-infected adults were enrolled at 96 outpatient centres in nine countries. Eligible participants were aged 18 years or older and on a regimen of 50 mg dolutegravir, 600 mg abacavir, and 300 mg lamivudine (fixed-dose combination or multi-tablet regimen); had an estimated glomerular filtration rate of 50 mL/min or higher; and had been virologically suppressed (plasma HIV-1 RNA <50 copies per mL) for 3 months or more before screening. We randomly assigned participants (1:1), using a computer-generated randomisation sequence, to switch to co-formulated bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg; herein known as the bictegravir group), or to remain on dolutegravir, abacavir, and lamivudine (herein known as the dolutegravir group), once daily for 48 weeks. The investigators, participants, study staff, and individuals assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or higher at week 48 (according to the US Food and Drug Administration snapshot algorithm); the prespecified non-inferiority margin was 4%. The primary efficacy and safety analyses included all participants who received at least one dose of study drug. This study is ongoing but not actively recruiting participants and is in the open-label extension phase, wherein participants are given the option to receive bictegravir, emtricitabine, and tenofovir alafenamide for an additional 96 weeks. This trial is registered with ClinicalTrials.gov, number NCT02603120.
Between Nov 11, 2015, and July 6, 2016, 567 participants were randomly assigned and 563 were treated (282 received bictegravir, emtricitabine, and tenofovir alafenamide, and 281 received dolutegravir, abacavir, and lamivudine). Switching to the bictegravir regimen was non-inferior to remaining on dolutegravir, abacavir, and lamivudine for the primary outcome: three (1%) of 282 in the bictegravir group had HIV-1 RNA of 50 copies per mL or higher at week 48 versus one (<1%) of 281 participants in the dolutegravir group (difference 0·7%, 95·002% CI -1·0 to 2·8; p=0·62). Treatment-related adverse events were recorded in 23 (8%) participants in the bictegravir group and 44 (16%) in the dolutegravir group. Treatment was discontinued because of adverse events in six (2%) participants in the bictegravir group and in two (1%) participants in the dolutegravir group.
The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide might provide a safe and efficacious option for ongoing treatment of HIV-1 infection.
Gilead Sciences.
Molina JM
，Ward D
，Brar I
，Mills A
，Stellbrink HJ
，López-Cortés L
，Ruane P
，Podzamczer D
，Brinson C
，Custodio J
，Liu H
，Andreatta K
，Martin H
，Cheng A
，Quirk E
... -
《Lancet HIV》
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