CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

analyses of genotypic data were performed to identify Baseline IN mutations impacting Day 8 AR. Derived IN resistance correlates were tested on Week 24 and Week 48 AR (ITT-E, %<50 c/mL, ‘Snapshot’) using combined V3/4 AR data (N=213). Results: At Day 8, no definite DTG FC cut-offs for No AR and Full AR were identified due to limited numbers of non-responders and few viruses with high DTG FC. A high correlation between mutations at position G140 and Q148 was confirmed ( P <0.001). Three Baseline IN resistance mutation groups were identified as predictors of Day 8 AR which remained associated with response at Weeks 24 and 48 in V3: No Q148 (includes Y143, N155, T66, E92 and virus with only historic IN primary mutations), Q148+1 and Q148+2 (of one or two or more of specific secondary mutations G140A/C/S, L74I, or E138A/K/T). Integrated V3/4 Week 24 AR rates by these derived mutation groups were 78%, 52%, and 24%, respectively; a similar AR pattern was seen at Week 48 with 70%, 48%, and 28%(ITT-E, %<50c/mL by Snapshot). Conclusions: The three derived baseline IN genotypic groups (No Q148 mutations, Q148 +1, and Q148 +2) were good predictors for DTG responses through Week 48, and thus provide guidance for the clinical use of DTG in patients with INI-resistant virus. Response rates were maintained between Week 24 and 48 for all three IN genotypic groups. 610 Discordant Predictions Could Impact Dolutegravir Use Upon Raltegravir Failure Kristof Theys 1 ; Ana B. Abecasis 2 ; Pieter Libin 1 ; Perpétua Gomes 2 ; Joaquim Cabanas 3 ; Ricardo J. Camacho 1 ; KristelVan Laethem 1 the Portuguese HIV-1 Resistance Study Group 1 University of Leuven, Leuven, Belgium; 2 Universidade Nova de Lisboa, Lisbon, Portugal; 3 Hospital Egas Moniz, Lisbon, Portugal Background: The latest integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) has been approved for HIV-1 patients with resistance to INSTIs raltegravir (RAL) and elvitegravir (EVG). While expanding therapeutic options, the decision for DTG use in this setting should be informed by the presence of baseline mutational patterns. Methods: Integrase sequences of 216 HIV-1 infected patients failing therapy containing RAL were collected. An exhaustive list of INSTI resistance-associated mutations (RAMs) was defined based on the IAS-USA 2013 list, resistance interpretation systems ANRS v23, HIVdb v7.0 and Rega v9.1.0, and on FDA and EMA package inserts of RAL, EVG and DTG. Mutation patterns were categorized into resistance levels scored by ANRS, HIVdb, Rega, and two additional categorization schemes (DTG-1 and DTG-2) derived from FDA and EMA package inserts. Results: One or more INSTI RAMs was observed in 188 patients (87%), with 43 of 79 defined RAMs detected and a major INSTI RAM present in 132 patients (62%). The most prevalent RAL signature mutations were N155H (25.4%), Q148H (16.2%) and Y143R (8.3%). Predictied RAL activity upon failure displayed low levels of discordance (8.8%), and concordant scores were mainly high-level resistant (R) (52.3%) or susceptible (S) (36.6%), and less intermediate resistant (IR) (2.3%). The majority of patients were still concordantly scored susceptible to DTG (57.8%). A total of 141 unique INSTI mutational patterns were classified into 6 groups according to mutations at signature positions 143, 148 and 155. A signature mutation was not detected in 96 patients (44%), of which 97%was concordantly scored susceptible, whereas patients displaying the N155H pathway (21.88%) showed concordant susceptible scores in 66% of patients. Patients harboring the Q148 pathway (18.5%) were concordantly scored (I)R in 37.5%. Nevertheless, disagreement between all five systems occurred for 34.7% of patients. Although concordant (I)R DTG scores were only obtained in 7.4% of patients, individual interpretation systems scored (I) R more often, from 20.4% for DTG-2 to 31% for HIVdb and DTG-1. Highest levels of discordance were observed for Y143 (95.8%) and Q148 (62.5%) pathways and for patterns of multiple signature mutations (88.9%). Conclusions: DTG may potentially be effective in most HIV-1 patients failing RAL. However, a consensus on interpreting the extent of residual activity is highly resistance pathway specific, which could lead to uncertainty in individual patient management.

Poster Abstracts

385

CROI 2015