1381. No Emergent Resistance in HIV-1 Infected Virologically-Suppressed Subjects Who Switched to R/F/TAF
Session: Poster Abstract Session: HIV: Antiretroviral Therapy
Friday, October 6, 2017
Room: Poster Hall CD
Posters
  • Porter HIV-1 IDWeek 2017 Poster_Final.pdf (189.9 kB)
  • Background: GS-US-366-1216 and GS-US-366-1160 are randomized, double-blind, phase 3b studies evaluating the safety and efficacy of switching to rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF) from R/F/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/F/TDF, respectively, in HIV-1-infected virologically-suppressed subjects. At Week 48, switching to R/F/TAF was non-inferior to staying on R/F/TDF (94% vs. 94%, respectively) or EFV/F/TDF (90% vs. 92%) for HIV-1 RNA <50 c/mL (virologic success) by FDA snapshot analysis. Here, we present integrated resistance analyses of these two studies through Week 48.

    Methods:¬†Historical genotypes were collected when available. Subjects in the resistance analysis population (subjects with HIV-1 RNA ‚Č•400 c/mL at virologic failure, discontinuation, or Week 48) had genotypic/phenotypic analyses at failure for protease and reverse transcriptase (RT; PhenoSense GT, Monogram). Subjects with post-baseline resistance mutations detected had their baseline proviral DNA analyzed retrospectively (GenoSure Archive, Monogram).

    Results: Of the 1504 randomized and treated subjects, resistance development was analyzed for 7 subjects (0.9%; 7/754) on R/F/TAF, 1 subject (0.3%; 1/313) on R/F/TDF, and 2 subjects (0.5%; 2/437) on EFV/F/TDF. No R/F/TAF (0%) or R/F/TDF (0%) subjects developed primary NNRTI or NRTI resistance mutations. One EFV/F/TDF subject (0.2%; 1/437) developed primary NNRTI and NRTI resistance mutations (NNRTI: Y188L; NRTI: M184V). Three subjects on R/F/TAF had virologic rebound with mutations also detected at baseline by proviral DNA analysis. Historical genotypes were available for 527 subjects; virologic success rates were high among subjects with pre-existing mutations (Table 1).

    Table 1. Virologic success rates of subjects with mutations by historical genotype.

    RT Mutation

    Subjects with Success/Subjects with Mutation (%)

    R/F/TAF

    R/F/TDF

    EFV/F/TDF

    K101E

    1/1 (100%)

    0

    0

    K103N

    10/11a (91%)

    6/7a (86%)

    1/1 (100%)

    E138A/K

    2/3a (67%)

    2/2 (100%)

    0

    M184V

    1/2a (50%)

    1/1 (100%)

    0

    a1 subject discontinued prior to Week 48 with HIV-1 RNA <50 c/mL

    Conclusion: No emergent resistance to any of the components of R/F/TAF was detected through 48 weeks after switching. Virologic success rates were high among subjects with pre-existing mutations.

    Danielle Porter, Ph.D.1, Rima Kulkarni, BS2, Huyen Cao, MD2, Devi Sengupta, MD3 and Kirsten White, PhD2, (1)Gilead Sciences, Inc., Foster City, CA, (2)Gilead Sciences, Foster City, CA, (3)Gilead Sciences Inc., Foster City, CA

    Disclosures:

    D. Porter, Gilead Sciences, Inc.: Employee and Shareholder , Salary

    R. Kulkarni, Gilead Sciences, Inc.: Employee and Shareholder , Salary

    H. Cao, Gilead Sciences, Inc.: Employee and Shareholder , Salary

    D. Sengupta, Gilead Sciences Inc.: Employee and Shareholder , Salary

    K. White, Gilead Sciences, Inc.: Employee and Shareholder , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.