CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

was at Week 96 using the FDA snapshot algorithmwith a pre-specified non- inferiority margin of 8%. Bone mineral density (BMD) was measured by DXA and percentage change from baseline compared between treatment groups using ANOVA. Percentage changes from baseline in renal markers were compared between treatment groups using Wilcoxan rank sum test. Adverse events and tolerability were evaluated. Results: A total of 630 participants were randomized and treated in Study 1216 and 875 in Study 1160. In Studies 1216 and 1160 the median ages were 45 and 49 years, 10% and 13%women, 19% and 27% black respectively. In both studies, switching to RPV/FTC/TAF was non-inferior to continuing baseline therapy through week 96. Study 1216: 89% vs 88% (difference: 0.7%; 95% CI -4.3 to +5.8); Study 1160: 85% vs. 85% (difference 0%; 95% CI -4.8 to +4.8). No participant on RPV/FTC/TAF had treatment emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF who was found to have pre-existing NRTI and NNRTI resistance at baseline. Significant increases from baseline in hip and spine BMD and improvements in renal tubular markers were observed in the RPV/FTC/TAF groups compared to continued therapy (p <0.001, Table 1). Fanconi syndrome occurred in one subject on EFV/FTC/TDF, no renal tubulopathy cases occurred on RPV/FTC/TAF. Conclusion: Switching to RPV/FTC/TAF was safe and maintained high rates of viral suppression through 96 weeks with no cases of treatment emergent resistance. Switching patients to RPV/FTC/TAF is an effective option with improved safety in long-term follow-up.

c/ml and a CD4-nadir ≥ 200 cells/mm 3 . We analyzed which baseline patient characteristics were associated with VF. Because the number of events was small, only univariable analysis was possible (unpaired T-test and Mann Whitney U Test as appropriate). Results: The OT-population consisted of 95 patients, of whom 8 had VF. The analyses showed that mean (SD) log total HIV DNA/10^6 PBMCs (2.16 (0.53) versus 2.57 (0.40), p=0.037), median (Q1-Q3) CD4-nadir (380 (290-520) versus 260 (223-320) cells/mm 3 , p=0.011), and median (Q1-Q3) time between HIV-diagnosis and start cART (15 (1-38) versus 49 (27-64) months, p=0.015) all differed significantly at baseline between patients without and with VF respectively (Figure 1). Median (Q1-Q3) DTG plasma concentrations in the 8 patients with VF and 20 random patients without VF did not differ (1.65 (1.23-3.75) versus 1.70 (1.05-2.40) mg/mL, p=0.3). Other factors that were not associated with VF were the time that the patient had been virologically suppressed on cART before switching to DTG monotherapy, gender, the HIV-RNA zenith before cART initiation, nor did age, CD4-count, CD4:8-ratio and C-reactive protein and type of cART that was used (all at the start DTG monotherapy). Conclusion: In patients using DTG maintenance monotherapy, a larger HIV reservoir, lower CD4-nadir and longer time to cART initiation were associated with VF. This study supports that starting treatment early limits the viral reservoir and may facilitate therapy simplification strategies.

Poster Abstracts

506 RESISTANCE ANALYSES OF BICTEGRAVIR/EMTRICITABINE/TENOFOVIR ALAFENAMIDE SWITCH STUDIES Kristen Andreatta 1 , Madeleine Willkom 1 , Ross Martin 1 , Silvia Chang 1 , Hal Martin 1 , Hiba Graham 1 , Erin Quirk 1 , Kirsten L. White 1 1 Gilead Sciences, Inc, Foster City, CA, USA Background: The novel, unboosted integrase strand transfer inhibitor (INSTI) bictegravir (B) has been coformulated with the nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone emtricitabine (F)/tenofovir alafenamide (TAF). In 2 phase 3 clinical studies, stably suppressed HIV-1 infected adults who switched to B/F/TAF from regimens consisting of either a boosted protease inhibitor (PI) + 2 NRTIs (N=290; Study 1878) or the INSTI dolutegravir (DTG) + NRTIs abacavir (ABC)/lamivudine (3TC) (N=282; Study 1844) had low rates of virologic failure (VF; HIV-1 RNA ≥50 copies/mL by snapshot analysis) through week (W) 48, and switching was noninferior to comparator arms. Here, integrated resistance analyses are described. Methods: Available historical plasma HIV-1 RNA genotypes and retrospective proviral DNA genotyping of baseline viral isolates were analyzed. Viral isolates from patients with HIV-1 RNA ≥200 copies/mL at confirmed VF, discontinuation, or W48 were analyzed for protease (PR), reverse transcriptase (RT), and integrase (IN) genotype and phenotype. Results: Of the 572 patients who switched to B/F/TAF, pretreatment historical genotypes and/or retrospective proviral DNA genotypes of baseline viral isolates were obtained from 394 patients for PR/RT and from 158 patients for IN. Preexisting primary INSTI resistance (-R), NRTI-R, nonnucleoside RT inhibitor (NNRTI)-R, and PI-R substitutions were observed in 0.6% (1/158), 14.0% (55/394), 18.3% (72/394), and 6.3% (25/394), respectively. Pre-switch resistance to F and/or TAF was retrospectively detected at baseline in 8.9% (35/394) of patients and consisted of K65N/R (n=5), M184V/I (n=30), and/or ≥3

505 FACTORS PREDICTING VIROLOGICAL FAILURE DURING DOLUTEGRAVIR MAINTENANCE MONOTHERAPY Ingeborg Wijting 1 , Sofie L. Rutsaert 2 , Casper Rokx 1 , David M. Burger 3 , Elrozy Andrinopoulou 1 , Linos Vandekerckhove 2 , Bart Rijnders 1 1 Erasmus University Medical Center, Rotterdam, Netherlands, 2 HIV Cure Research Center, Ghent University, Ghent, Belgium, 3 Radboud University, Nijmegen, Netherlands Background: In the DOMONO-study (CROI 2017 451LB), dolutegravir (DTG) monotherapy was non-inferior to combination antiretroviral therapy (cART) in maintaining viral suppression during 24 weeks. However, the study had to be discontinued prematurely as 3 patients on DTG monotherapy developed integrase inhibitor resistance. Data about clinical and virological factors associated with virological failure (VF) are scarce. We aim to determine factors associated with VF during DTG maintenance monotherapy. Methods: DOMONO (NCT02401828) was a randomized clinical non-inferiority trial, randomizing HIV-1 patients suppressed on cART to DTG monotherapy either immediately or after 24 weeks of continued cART. Eligible patients were suppressed on cART for at least 6 months, with an HIV-RNA zenith < 100.000

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