Background: GS-US-236-0112 and GS-US-292-0106 are international, ongoing, phase 2/3, open-label, single arm, 48-week studies evaluating the safety and efficacy of the integrase inhibitor-based single-tablet regimens (STRs) elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) in HIV-1 infected treatment-naïve adolescents. Here, we present resistance results from a planned Week 24 interim analysis.
Methods: Genotypic analyses of HIV-1 protease (PR), reverse transcriptase (RT) and integrase (IN; GS-US-292-0106 only) were performed at screening for both studies. Subjects with resistance to study drugs were excluded. Subjects in the postbaseline resistance analysis population (subjects with HIV-1 RNA ≥400 copies/mL at virologic failure) had genotypic/phenotypic analyses at failure for PR, RT, and IN.
Results: The Week 24 interim analysis included 21 subjects on E/C/F/TDF and 23 subjects on E/C/F/TAF. Most subjects on E/C/F/TDF had HIV”‘1 subtype C (47.6%, 10/21) or B (38.1%, 8/21) with subtype AE also present (14.3%, 3/21). Most subjects on E/C/F/TAF had HIV”‘1 subtype A1 (56.5%, 13/23) with the remainder having subtype AE (17.4%, 4/23), B (17.4%, 4/23), D (4.3%, 1/23), or complex mixtures (4.3%, 1/23). HIV-1 subtype distribution correlated with geography (A1, Uganda; AE, Thailand; B, USA; C, South Africa). Resistance mutations detected at baseline (not excluded at screening) are shown in Table 1. At Week 24, 85.7% (18/21) of subjects on E/C/F/TDF and 91.3% (21/23) on E/C/F/TAF had virologic success (HIV-1 RNA <50 c/mL) by FDA snapshot. Virologic response rates were similar across subtypes. Enrolled subjects with pre-existing IN-, NNRTI-, NRTI-, and PI-associated resistance mutations had virologic response rates similar to the overall study population (Table 1). One subject on E/C/F/TDF (4.8%, 1/21) and no subjects on E/C/F/TAF (0/23) met the criteria for postbaseline resistance analysis; no emergent resistance was detected. No subjects in either study experienced suboptimal virologic response.
Conclusions: In this Week 24 interim analysis of two clinical trials in treatment-naïve adolescents, the E/C/F/TDF and E/C/F/TAF STRs demonstrated efficacy against diverse HIV-1 subtypes with no emergent resistance. E/C/F/TDF and E/C/F/TAF are potentially effective treatment options for HIV-infected adolescent populations globally.