Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial

Daar, Eric S.; DeJesus, Edwin; Ruane, Peter; Crofoot, Gordon; Oguchi, Godson; Creticos, Catherine; Rockstroh, Jürgen K.; Molina, Jean‐Michel; Koenig, Ellen; Liu, Ya-Pei; Custodio, Joseph M.; Andreatta, Kristen; Graham, Hiba; Cheng, Andrew; Martin, Hal; Quirk, Erin

doi:10.1016/s2352-3018(18)30091-2

Cited by 125 publications

(153 citation statements)

References 23 publications

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“…4) [18–22] and were eligible for resistance testing ( n = 14), no treatment-emergent resistance (genotypic [10, 22] or phenotypic [10]) was evident to any of the STR antiretrovirals [10, 22], irrespective of HIV-1 subtype (B or non-B) or pre-existing resistance [23]. Findings were generally similar for corresponding recipients of the dolutegravir- or boosted PI- or INSTI-based comparator regimens in these trials [18–22], although a RAM developed in the reverse transcriptase in one recipient of a ritonavir-boosted PI plus dual NRTI regimen (L74V) [20] and one recipient of elvitegravir/cobicistat/emtricitabine/tenofovir AF (M184M/I/V) [22]. …”

Section: Pharmacodynamic Propertiesmentioning

confidence: 99%

“…4.2) adults with HIV-1 infection, as evaluated in five randomized, active comparator-controlled, multicentre, phase 3, noninferiority studies of double-blind [18, 19, 21] or open-label [20, 22] design. The trials enrolled men and women (or just women [22]) with an estimated GFR (eGFR) of ≥ 30 [18] or ≥ 50 [19–22] mL/min; chronic HCV infection was permitted where specified [18, 20, 21]. Across trials, patients were predominantly men (83–90% in mixed-sex studies); some data are from abstracts/posters [22, 27, 28].…”

Section: Therapeutic Efficacymentioning

confidence: 99%

“…The efficacy of switching treatment-experienced adults (specifically women [22]) with virological suppression from their current ART regimen to bictegravir/emtricitabine/tenofovir AF has been evaluated in three phase 3 trials [20–22]. Patients must have maintained a viral load of < 50 copies/mL for ≥ 3 [21] or ≥ 6 [20, 22] months and have been on a stable ART regimen comprising a dual NRTI backbone plus either a PI (boosted atazanavir [20, 22] or darunavir [20]) or an INSTI (dolutegravir [21] or boosted elvitegravir [22]).…”

Section: Therapeutic Efficacymentioning

confidence: 99%

“…Patients must have maintained a viral load of < 50 copies/mL for ≥ 3 [21] or ≥ 6 [20, 22] months and have been on a stable ART regimen comprising a dual NRTI backbone plus either a PI (boosted atazanavir [20, 22] or darunavir [20]) or an INSTI (dolutegravir [21] or boosted elvitegravir [22]). Where specified, patients with resistance to the NRTI components [20, 21] or to dolutegravir [21] were excluded; one of the studies [21] also excluded patients with chronic HBV infection (as the comparator regimen would not have provided adequate efficacy against the virus). In the trial in which patients had baseline virological suppression with a dolutegravir-based regimen, the regimen consisted of dolutegravir, abacavir and lamivudine taken most commonly as an STR (Table 2) [21] and is thus hereafter referred to as dolutegravir/abacavir/lamivudine.…”

Section: Therapeutic Efficacymentioning

confidence: 99%

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Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection

Deeks

2018

Drugs

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Bictegravir is a new integrase strand transfer inhibitor (INSTI) with a high genetic barrier to the development of HIV-1 resistance. The drug is co-formulated with the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (AF) in a single-tablet regimen (STR) for the once-daily treatment of HIV-1 infection in adults (bictegravir/emtricitabine/tenofovir AF; Biktarvy®). In phase 3 trials, bictegravir/emtricitabine/tenofovir AF was noninferior to dolutegravir-based therapy (dolutegravir/abacavir/lamivudine or dolutegravir plus emtricitabine/tenofovir AF) in establishing virological suppression in treatment-naïve adults through 96 weeks’ treatment and, similarly, was noninferior to ongoing dolutegravir/abacavir/lamivudine or boosted elvitegravir- or protease inhibitor (PI)-based therapy in preventing virological rebound over 48 weeks in treatment-experienced patients. No resistance emerged to any of the antiretrovirals in the STR. Bictegravir/emtricitabine/tenofovir AF is generally well tolerated, requires no prior HLA-B*5701 testing (making it more suitable for ‘rapid start’ treatment), fulfils the antiretroviral regimen requirement for patients with hepatitis B virus (HBV) co-infection (i.e. contains tenofovir AF and emtricitabine, both of which are active against HBV) and can be used in renally impaired patients with creatinine clearance (CRCL) ≥ 30 mL/min. Thus, although cost-effectiveness analyses would be beneficial, current data indicate that bictegravir/emtricitabine/tenofovir AF is a convenient initial and subsequent treatment option for adults with HIV-1 infection, including those co-infected with HBV, and provides the first non-pharmacologically boosted, INSTI-based, triple-combination STR suitable for patients with CRCL 30–50 mL/min.

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Section: Pharmacodynamic Propertiesmentioning

confidence: 99%

Section: Therapeutic Efficacymentioning

confidence: 99%

Section: Therapeutic Efficacymentioning

confidence: 99%

Section: Therapeutic Efficacymentioning

confidence: 99%

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Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection

Deeks

2018

Drugs

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“…20 The switch to TAFcontaining regimens is effective in maintaining HIV and HBV suppression in HIV/HBV co-infection. 52 …”

Section: When and How To Switchmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

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518

287

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IMPORTANCE Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. OBJECTIVE To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. EVIDENCE REVIEW New evidence collected since the International Antiviral Society–USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. FINDINGS ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. CONCLUSIONS AND RELEVANCE Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

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Risk of dyslipidaemia in people living with HIV who are taking tenofovir alafenamide: a systematic review and meta‐analysis

Yoo,

Jung,

Kim

et al. 2024

J Int AIDS Soc.

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IntroductionAmong many antiretroviral drugs, tenofovir alafenamide is used extensively in combination regimens of tenofovir/emtricitabine or tenofovir/emtricitabine/bictegravir. However, concerns have arisen about the potential of tenofovir alafenamide to exacerbate hyperlipidaemia. This meta‐analysis evaluates the relationship between tenofovir alafenamide use and lipid‐profile alterations in people living with HIV.MethodsWe searched PubMed, Ovid MEDLINE, EMBASE and the Cochrane Library to identify studies on changes in cholesterol levels (e.g. total cholesterol, low‐density and high‐density lipoprotein cholesterol, and triglycerides) in people living with HIV who received treatment with a regimen containing tenofovir alafenamide (data collected 31 March 2023, review completed 30 July 2023). Potential risk factors for worsening lipid profile during treatment with tenofovir alafenamide were also evaluated.ResultsSixty‐five studies involving 39,713 people living with HIV were selected. Significant increases in total cholesterol, low‐density and high‐density lipoprotein cholesterol, and triglycerides were observed after treatment with tenofovir alafenamide. Specifically, low‐density lipoprotein cholesterol (+12.31 mg/dl) and total cholesterol (+18.86 mg/dl) increased markedly from the third month of tenofovir alafenamide use, with significant elevations observed across all time points up to 36 months. Comparatively, tenofovir alafenamide regimens resulted in higher lipid levels than tenofovir disoproxil fumarate regimens at 12 months of use. Notably, discontinuation of the tenofovir alafenamide regimen led to significant decreases in low‐density lipoprotein cholesterol (–9.31 mg/dl) and total cholesterol (–8.91 mg/dl). Additionally, tenofovir alafenamide use was associated with increased bodyweight (+1.38 kg; 95% confidence interval: 0.92–1.84), which became more pronounced over time. Meta‐regression analysis identified young age, male sex and low body mass index as risk factors for worsening cholesterol levels in individuals treated with tenofovir alafenamide.ConclusionsTenofovir alafenamide use in people living with HIV is associated with significant alterations in lipid profile.

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Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial

Cited by 125 publications

References 23 publications

Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection

Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Risk of dyslipidaemia in people living with HIV who are taking tenofovir alafenamide: a systematic review and meta‐analysis

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