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, phase 3, non-inferiority trial

Molina, Jean‐Michel; Ward, Douglas J.; Brar, Indira; Mills, Anthony; Stellbrink, Hans‐Jürgen; López‐Cortés, Luis F.; Ruane, Peter; Podzamczer, Daniel; Brinson, Cynthia; Custodio, Joseph M.; Liu, Hui; Andreatta, Kristen; Martin, Hal; Cheng, Andrew; Quirk, Erin

doi:10.1016/s2352-3018(18)30092-4

Cited by 146 publications

(186 citation statements)

References 13 publications

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“…361 nmol/L); Sect. 2]; moreover, the pharmacokinetic profiles of the other drugs in the STR were consistent with historical data in patients infected with HIV-1 [18–21]. …”

Section: Pharmacokinetic Propertiessupporting

confidence: 67%

“…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%

“…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%

“…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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“…361 nmol/L); Sect. 2]; moreover, the pharmacokinetic profiles of the other drugs in the STR were consistent with historical data in patients infected with HIV-1 [18–21]. …”

Section: Pharmacokinetic Propertiessupporting

confidence: 67%

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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“…Patients taking TDF-containing regimens have a greater initial decline in bone mineral density than those who take a TAF- or abacavir-containing regimen. 1,20,38 Accordingly, TDF is not recommended for patients with osteopenia or osteoporosis (evidence rating BIII). Abacavir does not require dose adjustment based on renal function.…”

Section: Recommended Initial Regimensmentioning

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

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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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