CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

Oral Abstracts

42 PATHWAYS OF RESISTANCE IN SUBJECTS FAILING DOLUTEGRAVIR MONOTHERAPY José L. Blanco 1 , Celia Oldenbuettel 2 , Réjean Thomas 3 , Josep Mallolas 1 , Eva Wolf 4 , Bluma Brenner 5 , Christoph D. Spinner 6 , Mark A. Wainberg 5 , Esteban Martinez 1 , for the Redo Group 1 Hosp Clinic Barcelona, Barcelona, Spain, 2 MVZ Karlsplatz, HIV Rsr and Clinical Care Cntr, München, Germany, 3 Clinique Médicale l’Actuel, Montreal, QC, Canada, 4 MUC Rsr, Munich, Germany, 5 McGill Univ, Montreal, QC, Canada, 6 Univ Hosp Klinikum Rechts der Isar, Munich, Germany Background: Dolutegravir (DTG) is a second generation InSTI that has shown in both preclinical and clinical studies to have a higher barrier to resistance than first generation InSTIs (RAL and EVG).To date, no InSTI resistance-associated mutations (RAMs) have been reported in ART-naïve persons receiving DTG through 144 weeks of follow-up in clinical trials and very few cases has been reported in INSTI-naïve subjects among pretreated individuals. Our objective was to identify and characterize different pathways of resistance in subjects failing a DTG-monotherapy (DTG-M) in four large clinical cohorts Methods: This is an international, multi-cohort, retrospective study. All subjects with no prior InSTI virological failure (InSTI-VF) failing DTG-M were included in this analysis. Virological failure (VF) was defined as two plasma viral loads (VL) above 50 cp/mL. Genotypic resistance mutations could be detected by: (i) plasma population sequencing (PS); (ii) plasma ultra-deep sequencing test (UDS); peripheral blood mononuclear cell population sequencing (PBMC-PS); and PBMC-UDS Results: Three large clinical cohorts in Munich, Montreal and Barcelona were included in this analysis. A total of 178 ART-experienced subjects with no prior InSTI-VF changed from different ART-regimens to DTG monotherapy (DTG-M). Eleven (6.1%) had VF and 7 (3.9%) selected any InSTI-RAMs . Two of 7 were women, median (range) of previous VF 1 (0-8; 3: 0VF; 1:1VF; 3≥4). InSTI prior DTG was: 3 none, 3 RAL and 1 EGV. VL by the time of starting DTG-M was: 5= below the lower limits of detection (LLOD), 1=249 cp/mL and 1=21 cp/ mL. Reasons for switch to DTG-Mwere: simplification (n=2), DDI (n=3), patient decision (n=3), toxicity (n=1), VF (n=1); 5 patients had at least one LLOD before VF. Median (range) time and first VL by the time of VF were 12 weeks (0-28) and 306 copies/mL (55-26180), respectively. Time to first detection of DTG-RAMs was 28 weeks (2-32). The three different pathways by the time of VF were: 148R/H in 3 patients, 155H in 2, and 118R in 2 Conclusion: Virological failure and selection of InSTI-RAMs are uncommon but they may exist in patients with no prior InSTI virological failure subjects on DTG-monotherapy. Different pathways, similar to first-generation InSTIs (RAL and EVG), 148R/H, 155H, and 118R were identified in these cases 43 PREVALENCE AND IMPACT OF PRETREATMENT DRUG RESISTANCE IN THE ANRS 12249 TASP TRIAL Anne Derache 1 , Collins C. Iwuji 2 , Siva Danaviah 1 , Anne-Geneviève Marcelin 3 , Vincent Calvez 3 , Tulio de Oliveira 4 , François Dabis 5 , Deenan Pillay 1 , for the ANRS 12249 Treatment as Prevention Trial 1 Africa Hlth Rsr Inst, Mtubatuba, South Africa, 2 Univ Coll London, London, UK, 3 Pitie-Salpetriere Hosp, Paris, France, 4 Univ of KwaZulu-Natal, Durban, South Africa, 5 Univ de Bordeaux, Bordeaux, France Background: Increasing use of antiretroviral therapy (ART) in Test and Treat strategies may lead to higher levels of acquired and transmitted drug resistance (DR) and compromise ART efficacy for individual or population benefits. We assessed prevalence of pre-treatment DR (PDR) and impact on viral suppression (VS) [viral load (VL)<400 copies/mL] among ART naïve participants who initiated 1st-line ART within the ANRS 12249 cluster-randomized trial. Methods: DR testing was done on samples from 1340 participants who were recently infected (RIn) during the trial or chronically infected (CIn) at entry (March 2012–June 2016). Pol gene Sanger sequencing was done on dried blood spots from 195 RIn participants who had not linked to HIV care. Full HIV genome sequencing using the MiSeq platformwas done on plasma samples from 77 RIn and 1069 Cln participants who linked to care, of whom 838 initiated ART. Minority variants were called at a 2% level (Geneious and MiCall softwares). Cox regression was used to estimate hazard ratios (HR) for VS. Results: Overall PDR prevalence was 8,4% (95%CI=6,7-10%) and 17,8% (95%CI=15,1-20,5%) at 20% and 2% detection levels respectively; these proportions were similar between RIn and CIn participants. Among participants with PDR, 88% had only 1 or 2 DR mutations, associated with NNRTI resistance in 73% of the cases, and 61%were detected as a majority variant (>20%). 13,5% and 8,8%were associated with NRTI and PI resistance, respectively, with 90% of them being minority variants (<20%) for both NRTI and PI. Among RIn participants with PDR, 92%were associated with a single ARV class (mostly NNRTI). Among 838 adults initiating ART, median follow-up time on ART was 16 months (m); median time to VS was 3m (IQR 2.8-3.9). Cumulative VS at 12mwas 97%. After adjusting for sex, age, baseline VL and adherence, there was no evidence that PDR was associated with VS (adjusted (a)HR 0.96, 95%CI 0.75-1.23 and aHR=1.12, 95%CI 0.89-1.42, for majority and minority variants, respectively, vs no mutations). High baseline VL (>100,000 vs <10,000) was associated with a decreased rate of VS (aHR 0.75; 0.62-0.91) and good adherence (≥95% vs <95%) was associated with an increased rate of VS (aHR 1.36; 1.11-1.66). Conclusion: The prevalence of PDR approached 10% at >20% representation among RIn and CIn participants, while deep sequencing identified double the prevalence. Longer term follow up is needed to assess the lack of virological impact of PDR. 44LB PHASE III SWORD 1&2: SWITCH TO DTG+RPV MAINTAINS VIROLOGIC SUPPRESSION THROUGH 48 WKS Josep M. Llibre 1 , Chien-Ching Hung 2 , Cynthia Brinson 3 , Francesco Castelli 4 , Pierre-Marie Girard 5 , Lesley Kahl 6 , Elizabeth Blair 7 , Brian Wynn 8 , Kati Vandermeulen 9 , Michael Aboud 7 1 Univ Hosp Germans Trias, Badalona, Barcelona, Spain, 2 Natl Taiwan Univ Hosp, Taipei, Taiwan, 3 Central Texas Clinical Rsr, Austin, TX, USA, 4 ASST Spedali Civili di Brescia, Brescia, Italy, 5 Saint- Antoine Hosp, Paris, France, 6 ViiV Hlthcare, Brentford, Middlesex, UK, 7 ViiV Hlthcare, Rsr Triangle Park, NC, USA, 8 ViiV Hlthcare, Collegeville, PA, USA, 9 Janssen, Beerse, Belgium Background: The requirement for life-long antiretroviral therapy (ART) of HIV infection has highlighted interest in 2-drug regimens (2DR) to minimize cumulative drug exposure. Dolutegravir’s (DTG) potency, safety and resistance barrier make it an optimal core agent for 2DR. Rilpivirine’s (RPV) safety, tolerability and efficacy in switch regimens make it an ideal potential partner. Methods: Two identical open-label, multicenter, global, phase III, non-inferiority studies evaluated the efficacy and safety of switching from a 3 or 4-drug current antiretroviral regimen (CAR) to DTG+RPV once daily in HIV-1-infected adults, with HIV-1 RNA<50c/mL (VL<50c/mL) for at least 12 months and no history of virologic failure. Participants (pts) were randomized 1:1 (stratified by baseline 3rd agent class; age.

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CROI 2017