Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection

Abstract

Once-daily EVG/COBI/FTC/TDF achieved and maintained a high rate of virologic suppression with fewer central nervous system and psychiatric adverse events compared to a current standard-of-care regimen of EFV/FTC/TDF.

Characterization of the R263K Mutation in HIV-1 Integrase That Confers Low-Level Resistance to the Second-Generation Integrase Strand Transfer Inhibitor Dolutegravir

“…Raltegravir (RAL) was the first INSTI to be approved for therapy in 2007 (64) and is safe and efficient in both treatment-naïve and treatment-experienced subjects (11,17,23,35,49,62,63). Elvitegravir (EVG) is another INSTI currently in advanced clinical trials (10,12,77).…”

Cobicistat Boosts the Intestinal Absorption of Transport Substrates, Including HIV Protease Inhibitors and GS-7340, In Vitro

“…Clinically, COBI increases systemic levels of the CYP3A substrates midazolam and elvitegravir (EVG) to a similar extent as RTV (7, 13), and coadministration with COBI allows EVG to be administered once daily (16). A fixed-dose, once-daily, single-tablet regimen that includes EVG/COBI and the nucleos(t)ide reverse transcriptase inhibitors tenofovir disoproxil fumarate and emtricitabine, colloquially known as "QUAD," has completed registrational trials, including meeting its primary endpoints in phase 3 studies (2,3,19,20).…”

“…Clinically, COBI increases systemic levels of the CYP3A substrates midazolam and elvitegravir (EVG) to a similar extent as RTV (7, 13), and coadministration with COBI allows EVG to be administered once daily (16). A fixed-dose, once-daily, single-tablet regimen that includes EVG/COBI and the nucleos(t)ide reverse transcriptase inhibitors tenofovir disoproxil fumarate and emtricitabine, colloquially known as "QUAD," has completed registrational trials, including meeting its primary endpoints in phase 3 studies (2,3,19,20).Inhibition of efflux transporters expressed in the intestine can serve as a secondary mechanism for a pharmacoenhancer to increase systemic exposure to coadministered drugs by increasing their absorption. P-glycoprotein (Pgp; also known as multidrug resistance protein 1 [MDR1] or ATP-binding cassette subfamily B member 1 [ABCB1]) and the breast cancer resistance protein (BCRP; also known as ATP-binding cassette subfamily G member 2 [ABCG2]), both expressed at the apical side of the small intestine, have been highlighted by regulatory agencies and in the literature as key transporters affecting xenobiotic pharmacokinetics (5, 6).…”

Elvitegravir, A New HIV‐1 Integrase Inhibitor for Antiretroviral Therapy

“…The once-daily single tablet, stribild, showed potent and durable antiretroviral efficacy and favorable safety in clinical studies. Stribild demonstrated to produce a comparable level of virologic suppression with fewer adverse events compared with preferred regimens (co-formulated efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, and ritonavir-boosted atazanavir 300 mg plus co-formulated emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) [61][62][63]. Elvitegravir was granted approval as part of stribild by the US FDA in 2012 and EMA in 2013.…”