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

Abstract

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.

Clinical Impact and Cost-effectiveness of Genotype Testing at Human Immunodeficiency Virus Diagnosis in the United States

“…In conclusion, for people starting DTG-based regimens in the United States, obtaining a baseline genotype offers minimal clinical benefit; a similar conclusion is likely for BIC-based regimens [55]. Baseline genotypes provide no benefit to most adults with a new HIV diagnosis and only a very small increase in projected survival to those who do benefit.…”

Comparison of the Antiviral Activity of Bictegravir against HIV-1 and HIV-2 Isolates and Integrase Inhibitor-Resistant HIV-2 Mutants

“…Bictegravir is not currently available as a stand-alone INI; it is coformulated with emtricitabine and tenofovir alafenamide in the single-tablet regimen (STR) Biktarvy. Biktarvy exhibits several pharmacological properties that are distinct from other STRs; it does not require testing for the HLA-B*5701 polymorphism, and it is safe to use in patients with impaired kidney function (with creatinine clearance of Ն30 ml/min) (31,32). Through the inclusion of emtricitabine and tenofovir alafenamide, Biktarvy meets the requirements for treatment of HIV-infected patients who are coinfected with hepatitis B virus (55), which represents ϳ10% of all people living with HIV in West Africa (56)(57)(58)(59).…”

Tailor‐Made Amino Acids and Fluorinated Motifs as Prominent Traits in Modern Pharmaceuticals

“…In 2018, compound 487 received its first approval by the FDA for the treatment of HIV-1 infection in adults if used in combination with the reverse transcriptasei nhibitors (NRTIs) emtricitabine and tenofovir alafenamide. [189,190] For the synthesis of 487,amethodw ith 1-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid( 491)a st he key intermediate is presented in Schemes 64 and 65. Ac ondensation reactionb etween methyl 4-methoxy-3-oxobutanoate and 2,2-dimethoxy-N,N-dimethylethanamine at room temperature gave 488,w hich reacted with 2,2-dimethoxyethanamine to afford enamine 489.A ni ntermolecular cyclization reactionb etween 489 and dimethyl oxalate with the aid of LiHMDSp rovided pyridin-4(1H)-one 490,w hich was treated withL iOH to produce key intermediate 491 (Scheme64).…”