Infrequent Development of Drug Resistance in HIV-1-Infected Treatment-Naive Subjects after 96 Weeks of Treatment with Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide or Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir Disoproxil Fumarate. Issue 5 (July 2017)

• Record Type: Journal Article
• Authors: Margot, Nicolas; Cox, Stephanie; Das, Moupali; McCallister, Scott; Miller, Michael D; Callebaut, Christian
• Is Part Of: Antiviral therapy. Volume 22:Issue 5(2017)
• Page Start: 443
• Page End: 446
• Publication Date: 2017-07
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP3125
• Languages: English
• ISSNs: 1359-6535

Abstract

Background: Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) comprising elvitegravir, cobicistat, emtricitabine and TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/ml at week 48 that were maintained through week 96. A resistance analysis of the combined Phase III clinical studies through 96 weeks is described here. Methods: Genotypic and phenotypic susceptibility to antiretrovirals (ARVs) was evaluated for subjects with HIV-1 RNA ≥400 copies/ml at time of virological failure (VF) or early discontinuation. Results: Through week 96, VF resistance analyses were conducted for 24 subjects in each arm (2.8%, 24/866 and 2.8%, 24/867; for E/C/F/TAF and E/C/F/TDF arms, respectively). Primary resistance development to ARVs of the regimen occurred in 10 of 24 subjects in the E/C/F/TAF arm, and 8 of 24 subjects in the E/C/F/TDF arm (E/C/F/TAF: M184V/I, n =9; integrase strand-transfer inhibitor resistance-associated mutations [INSTI-RAMs], n =8; K65R/N, n =2; E/C/F/TDF: M184V/I, n =6; INSTI-RAMs, n =5; K65R/N, n =3). The emergent resistance mutations were similar between the treatment arms. Conclusions: E/C/F/TAF achieved a high level of virological suppression in HIV-1 treatment-naive subjects through 96 weeks of treatment, with infrequent resistance development and comparable genotypic changes across both the E/C/F/TAF and E/C/F/TDF treatment groups.