CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

and genotypic resistance tests (GRTs) for episodes of detectable viremia. In this analysis, we included episodes of detectable HIV RNA with paired GRTs after at least four months on ART, after which participants remained on the same regimen until a subsequent HIV RNA test. Our aimwas to identify relationships between HIVDR, adherence and resuppression. We defined HIVDR as intermediate or high-level resistance to any drug in the first line regimen using Stanford susceptibility scores. We calculated resuppression rates by HIVDR status, stratified by average adherence. We fit logistic regression models with robust standard errors with resuppression as the outcome and HIVDR as the predictor of interest, adjusting for sex, age, HIV RNA at first failure, average adherence, and regimen. Results: We analyzed 90 episodes of viremia. Median ART duration was 0.84 years, and 100%were on non-nucleoside reverse transcriptase inhibitors (NNRTI). Median log HIV RNA at first failure was 3.56 copies/mL. Median time between HIV RNA tests was 84 days. Forty-seven (52%) participants had HIVDR, with NNRTI mutations most common. 49/90 (54%) achieved resuppression, but the rate was significantly lower in those with versus without HIVDR (28% vs. 84%, P<0.001). When stratified by adherence, results were not significantly different (Figure). HIVDR remained a strong negative predictor of resuppression in a logistic regression model, adjusted for sex, age, HIV RNA at first failure, adherence, and regimen (OR 0.06, 95% CI 0.02 – 0.20, P<0.001). Adherence was not correlated with resuppression, and there was no significant interaction with HIVDR. Conclusion: HIVDR is an important driver of persistent virologic failure on first line ART. Current guidelines that focus on those with HIV RNA >1,000 copies/ mL and adherence support may fail to address this primary driver of treatment failure in the region.

through 48 weeks compared to standard 2NRTI+NNRTI (Std) ART in ART-naïve HIV-infected adults/children ≥5y with CD4<100 cells/ul. The impact of RAL intensification on HIV resistance in those initiating ART with low CD4 and high VL is unknown. Methods: Integrase (INT) was sequenced from Std+RAL samples with VL>1000 c/ml at week 12 , and reverse transcriptase (RT) sequenced in samples >1000 c/ml from both groups at week 48. INT/RT resistance was predicted using Stanford. Results: 1550 eligible patients were from Kenya, Uganda and Zimbabwe (Malawi samples not available) and randomized to Std+RAL (n=775) vs Std (n=775). Median baseline CD4 was 36 cells/ul and VL 275,700 c/ml (76%≥100,000 c/ml). At week 12, VL was <50 c/ml in 470/667 (69%) Std+RAL vs 334/685 (49%) Std (p<0.001). 45(7%) Std+RAL had VL>1000 c/ml, of whom INT genotypes were obtained in 30(67%) (median 55680 c/ml). The primary/ major accessory mutations R263K, T97A, L74M or N155H were found in 5, 5, 1, 1 respectively, translating into 1 with intermediate (T97A+R263K) and 1 with high-level (N155H) RAL resistance (7% of sequenced at week 12; 0.4% of randomized) (week-48 VL 22976 and <50 c/ml respectively). No patient had intermediate/high-level dolutegravir resistance. At 48 weeks, VL was <50 c/ ml in 527/654 (81%) Std+RAL vs 495/642 (77%) Std (p=0.12) and >1000 c/ml in 76(12%) vs 90(14%) respectively (p=0.20). RT genotypes were obtained in 69(91%) Std+RAL vs 82(91%) Std. K219E/Q (p=0.005), M41L (p=0.053), K101E/P (p=0.04) and P225H (p=0.008) were less common in Std+RAL. However, there was no evidence of differences between Std+RAL vs Std in intermediate/ high-level resistance to 3TC (overall 73%,p=0.23), ABC (49%,p=0.12), ZDV (13%,p=0.74), EFV/NVP (88%,p=0.16), RPV (46%,p=0.10) or ETR (39%,p=0.18), whereas there was marginally less intermediate/high-level resistance with Std+RAL to TDF (25% vs 39% Std, p=0.06). Conclusion: 12 week RAL intensification had no clinical benefit and did not substantially protect against developing clinically meaningful NRTI/ NNRTI resistance. Major INT mutations potentially compromising RAL, but not dolutegravir, occurred in very small numbers of those receiving 12 week RAL; whether this was transmitted or emergent is uncertain, as baseline INT sequencing was not performed.

Poster Abstracts

532 POOLED WEEK 48 EFFICACY AND BASELINE RESISTANCE: B/F/TAF IN TREATMENT-NAIVE PATIENTS Kirsten L. White , Rima Kulkarni, Madeleine Willkom, Ross Martin, Silvia Chang, Xuelian Wei, William Garner, Devi SenGupta, Hal Martin, Erin Quirk, Andrew Cheng Gilead Sciences, Inc, Foster City, CA, USA Background: Two phase 3, randomized, blinded, studies showed HIV-1 treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) had no emergent resistance and was non-inferior to abacavir/dolutegravir/ lamivudine (ABC/DTG/3TC, Study 1489) and DTG+F/TAF (Study 1490) in treatment-naïve subjects. Here, pooled efficacy analyses through W48 and the effect of baseline resistance on treatment response are described. Methods: Population sequencing of HIV-1 protease and reverse transcriptase was done at screening; resistance to study NRTIs was excluded. Baseline retrospective next generation sequencing of integrase (all randomized,

531 EFFECT OF 12-WEEK RALTEGRAVIR INTENSIFICATION OF FIRST-LINE ART ON HIV RESISTANCE Cissy Kityo 1 , Sarah Walker 2 , Immaculate Nankya 1 , Moira J. Spyer 2 , Eva Nabulime 1 , Mutsa Bwakura-Dangarembizi 3 , Linda Mipando 4 , Simon Wachira 5 , Anthony Etyang 6 , Godfrey Musoro 3 , Esther Nambi 1 , Kusum Nathoo 3 , Sarah Pett 2 , Diana Gibb 2 1 Joint Clinical Research Centre, Kampala, Uganda, 2 University College London, London, UK, 3 University of Zimbabwe, Harare, Zimbabwe, 4 University of Malawi, Blantyre, Malawi, 5 Moi University, Eldoret, Kenya, 6 KEMRI–Wellcome Trust Research Programme, Kilifi, Kenya Background: The REALITY trial (ISRCTN43622374) showed that 12-week raltegravir (RAL)-intensified ART (Std+RAL) was well tolerated, reduced VL faster through 24 weeks, but did not affect mortality or WHO 3/4 events

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