1509. Emergence of HIV-1 Drug Resistance Through Week 48 in the Global Women’s WAVES Study: Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF vs. Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF
Session: Poster Abstract Session: HIV: Antiretroviral Therapy
Friday, October 28, 2016
Room: Poster Hall
  • Kulkarni WAVES Study IDWeek 2016 Poster 1509_Final.pdf (389.9 kB)
  • Background: Women and those with non-B subtype HIV-1 are typically underrepresented in clinical trials. WAVES (GS-US-236-0128) is a double-blind phase 3b study evaluating the safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF; N=289) and atazanavir+ritonavir+FTC/TDF (ATV+RTV+FTC/TDF; N=286) in treatment-naïve HIV-1-infected women from the USA, Russia, Uganda, and 8 other countries. At Week 48, EVG/COBI/FTC/TDF had superior efficacy compared to ATV+RTV+FTC/TDF for HIV-1 RNA <50 copies/mL by FDA snapshot analysis. Here, we describe resistance development through Week 48 in women with virologic failure, and determine the impact of pre-existing mutations and polymorphic substitutions, as well as HIV-1 subtype, on viral suppression.

    Methods: Population genotypic and phenotypic analyses of HIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) were performed at Monogram Biosciences. Deep sequencing of PR, RT, and IN was performed by SeqIT GmbH & Co. Women were evaluated for resistance if they had HIV-1 RNA ≥400 copies/mL at confirmed virologic failure, discontinuation ≥Week 8, or Week 48, and, if evaluated, they had genotypic and phenotypic analyses at failure and baseline.

    Results: The proportion of women analyzed for resistance was fairly high and similar between treatment groups (6.2% EVG/COBI/FTC/TDF; 7.3% ATV+RTV+FTC/TDF). Emergent resistance was rare (0% EVG/COBI/FTC/TDF; 1% ATV+RTV+FTC/TDF: 3 with M184V/I in RT). Deep sequencing did not find additional resistance development. Pre-existing mutations did not lead to failure with resistance; those with the polymorphic T97A IN substitution and most with A62V in RT (a fitness compensatory mutation for K65R common in Russia) had HIV-1 RNA <50 copies/mL at Week 48, with no K65R development. Most subjects (428/575, 74%) had non-B HIV-1 and subtype did not affect outcome.

    Conclusion: Emergent resistance to study drugs was rare in this global study of women. This was despite having relatively large numbers of women who required resistance testing, compared to HIV-1 clinical trials with mostly men. Virologic failure with drug resistance was not a common risk for women in this study, including those infected with a non-B HIV-1 subtype.

    Rima Kulkarni, BS1, Sally Hodder, MD2, Huyen Cao, MD1, Silvia Chang, MS1, Michael Miller, PhD1 and Kirsten White, PhD1, (1)Gilead Sciences, Foster City, CA, (2)West Virginia University School of Medicine, Morgantown, WV


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

    S. Hodder, Gilead Sciences, Inc.: Consultant and Scientific Advisor , Research grant
    Bristol-Myers Squibb Company: Consultant and Scientific Advisor , Research grant
    Janssen Pharmaceuticals: Consultant and Scientific Advisor , Research grant
    ViiV Healthcare: Consultant and Scientific Advisor , Research grant
    Merck & Co., Inc.: Shareholder , Stock, stock options, bonds

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

    S. Chang, Gilead Sciences, Inc.: Employee and Shareholder , Salary

    M. Miller, 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. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.