Rare emergence of drug resistance in HIV-1 treatment-naïve patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks

Nicolas Margot; Stephanie Cox; Moupali Das; Scott McCallister; Michael D Miller; Christian Callebaut

doi:10.1016/j.jcv.2018.03.012

Rare emergence of drug resistance in HIV-1 treatment-naïve patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks

J Clin Virol. 2018 Jun:103:37-42. doi: 10.1016/j.jcv.2018.03.012. Epub 2018 Apr 2.

Authors

Nicolas Margot¹, Stephanie Cox², Moupali Das², Scott McCallister², Michael D Miller², Christian Callebaut²

Affiliations

¹ Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA. Electronic address: Nicolas.Margot@gilead.com.
² Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.

PMID: 29627709
DOI: 10.1016/j.jcv.2018.03.012

Abstract

Background: The single tablet regimen (STR) composed of elvitegravir (E), cobicistat (C), emtricitabine (F), and tenofovir alafenamide (TAF) (E/C/F/TAF) was compared to the STR composed of E, C, F, and tenofovir disoproxil fumarate (TDF) (E/C/F/TDF) in 2 phase 3 studies in 1733 HIV-1 infected treatment-naïve adults. Superior efficacy of E/C/F/TAF compared to E/C/F/TDF was demonstrated at Week 144 with 84% treatment success compared to 80%, respectively, along with significantly better outcomes of bone and renal safety.

Objectives: Analyze the emergence of HIV-1 resistance in treatment-naïve adults receiving E/C/F/TAF for 144 weeks.

Study design: We conducted an integrated resistance analysis of the 2 Phase 3 studies, comprising pretreatment HIV-1 sequencing for all participants (N = 1733) and post-baseline HIV-1 resistance analysis for participants with virologic failure (HIV-1 RNA ≥400 copies/mL).

Results: Primary resistance-associated mutations (RAMs) were observed pre-treatment in 7.4% (NRTI-RAMs), 18.1% (NNRTI-RAMs), and 3.3% (PI-RAMs) of enrolled subjects. Baseline HIV-1 subtype or pre-existing RAMs did not affect E/C/F/TAF treatment response at week 144. Virologic failure resistance analyses were conducted for 28/866 (3.2%) and 30/867 (3.5%) patients in the E/C/F/TAF and E/C/F/TDF arms, respectively. Over the 3-year study, the rate of resistance emergence remained low at 1.4% in each group (12/866 in E/C/F/TAF; 12/867 in E/C/F/TDF). Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-RAMs [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-RAMs [0.9%], K65R/N [0.5%]).

Conclusions: Resistance emergence was rare (1.4%) with similar patterns of emergent mutations in both groups. M184V/I was the most prevalent RAM (1.2% overall).

Keywords: HIV-1; Integrase strand transfer inhibitor resistance (INSTI-R); M184V; Tenofovir; Tenofovir alafenamide; Tenofovir disoproxil fumarate.

Publication types

Clinical Trial, Phase III
Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-HIV Agents / administration & dosage*
Anti-HIV Agents / pharmacology
Antiretroviral Therapy, Highly Active / methods*
Drug Resistance, Viral*
HIV Infections / drug therapy*
HIV Infections / virology*
HIV-1 / drug effects*
HIV-1 / genetics
HIV-1 / isolation & purification
Humans
Microbial Sensitivity Tests
Mutation
Mutation Rate
Prevalence
Sequence Analysis, DNA
Treatment Outcome

Substances

Anti-HIV Agents