CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Conclusion: In HIV-1–infected adults, switching to D/C/F/TAF led to low rates of cumulative virologic rebound over 48 weeks that was overall non-inferior to continuation of prior antiretroviral therapy. Low rebound rates, as well as improved bone safety and renal function, were observed with D/C/F/TAF versus control regardless of age, gender, or race.

baseline regimen. B/F/TAF was safe and well tolerated. This analysis supports the efficacy and safety of B/F/TAF in women observed in other B/F/TAF phase 2 and 3 studies. 501 EFFECT OF SWITCHING TO INTEGRASE INHIBITOR ON THE HIV RESERVOIR IN ILEUM BIOPSIES Sara Moron-Lopez 1 , Victor Urrea 1 , Jordi Navarro 2 , Maria C. Puertas 1 , Ariadna Torrella 2 , Maria Salgado 1 , Cristina Gálvez 1 , Bibiana Planas 2 , Linos Vandekerckhove 3 , Julià Blanco 1 , Manuel Crespo 2 , Javier Martinez-Picado 1 1 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 2 Vall d’Hebron Research Institute, Barcelona, Spain, 3 HIV Cure Research Center, Ghent University, Ghent, Belgium Background: Antiretroviral therapy optimization, including switching towards newer drugs, is a potential strategy to impact the HIV reservoir. A previous study suggested that switching to raltegravir might be associated with a decrease in total HIV-1 reservoir in blood after 48 weeks. However, the effect of integrase inhibitors on the HIV reservoir in tissues remains unknown. Thus, we evaluated the effect of switching from PI to dolutegravir (DTG) in cART on the HIV reservoir size in blood and ileum biopsies. Methods: INDOOR study (EUDRACT 2014-004331-39), a phase IV and opened clinical trial, randomly included 44 HIV-1 infected individuals on effective cART: 22 switched from PI to DTG based-cART (switch group), and 22 remained in PI-based regimens (control group). We collected four to eight endoscopic ileum biopsies and blood samples at weeks 0 and 24 from 33 subjects: 13 from the switch group and 20 from the control group. We performed a DTT/ EDTA-based treatment for epithelial layer removal followed by disruption of the tissue in absence of an enzymatic method to obtain an LPL cell suspension. CD45+ cells were subsequently purified by flow sorting. Total HIV DNA was determined by ddPCR in total peripheral blood mononuclear cells (PBMC) and in sorted leukocytes (CD45+ cells) from ileum biopsies. Statistical analyses were performed using R software and GraphPad. Results: This switching strategy was safe and well tolerated for all the patients, with no changes in viremia suppression (<50 cp/ml). Two patients, one from each arm, did not finish the study protocol. One patient with prior psychiatric history suffered a psychotic attack and the second one was lost to follow-up at the last visit; however, his last viral load was undetectable. We positively detected total HIV DNA in all samples, and a significant correlation of the HIV reservoir size was observed between tissue and blood samples (p=0.01, Rho=0.43 at week 0). Moreover, the reservoir size was consistently higher in tissue CD45+ cells than in PBMC in both groups (p<0.01). However, we did not observe significant longitudinal changes in the total HIV reservoir size, either in CD45+ cells of ileum biopsies or in PBMC, in any study group. Conclusion: The INDOOR study evaluated for the first time changes in the HIV reservoir size in ileum biopsies in individuals switched from PI- to DTG-based cART. This treatment switch was safe and well tolerated, but had no impact on the HIV reservoir size, measured as total HIV DNA, in CD45+ cells of ileum. 502 ANALYSIS OF HIV PATIENTS SWITCHING TO D/C/F/TAF BY PRIOR ARV TREATMENT EXPERIENCE Joseph J. Eron 1 , Chloe Orkin 2 , Jean-Michel Molina 3 , Erika Van Landuyt 4 , Erkki Lathouwers 4 , Romana Petrovic 4 , Richard E. Nettles 5 , Kimberley Brown 5 1 University of North Carolina Chapel Hill, Chapel Hill, NC, USA, 2 Royal London Hospital, London, UK, 3 St. Louis Hospital, Paris, France, 4 Janssen, Beerse, Belgium, 5 Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: HIV-1–infected patients enrolled in switch studies may not be representative of switch patients in clinical practice due to strict inclusion/ exclusion criteria. EMERALD allowed entry of patients with previous virologic failure (VF) or experience with multiple antiretrovirals (ARVs); we report Week 48 results by ARV treatment experience. Methods: EMERALD was a phase 3, randomized (2:1), non-inferiority trial that evaluated the efficacy and safety of switching to the single-tablet regimen darunavir/cobicistat/emtricitabine/ tenofovir alafenamide (D/C/F/ TAF; 800/150/200/10mg), or continuing use of a boosted protease inhibitor+F/ tenofovir disoproxil fumarate (control), in virologically suppressed, HIV-1– infected adults. Patients had viral load (VL) <50 copies(c)/mL for ≥2 months (1 VL ≥50 and <200 c/mL allowed in 12 months before screening) and, if available, absence of historical darunavir resistance mutations. Those with previous non-darunavir VF and prior experience with multiple ARVs were allowed. The primary endpoint was proportion of patients with virologic rebound (confirmed

Poster Abstracts

500 SWITCHING TO BICTEGRAVIR/EMTRACITABINE/TENOFOVIR ALAFENIMIDE (B/F/TAF) IN WOMEN Cissy Kityo 1 , Debbie Hagins 2 , Ellen Koenig 3 , Anchalee Avihingsanon 4 ,

Ploenchan Chetchotisakd 5 , Khuanchai Supparatpinyo 6 , Natalya Gankina 7 , Vadim Pokrovsky 8 , Evgenly Voronin 9 , Jeffrey L. Stephens 10 , Edwin DeJesus 11 , Hui Wang 12 , Erin Quirk 12 , Hal Martin 12 , Tariro Makadzange 12 1 Joint Clinical Research Centre, Kampala, Uganda, 2 Chatham CARE Center, Savannah, GA, USA, 3 Instituto Dominicano de Estudios Virológicos, Santo Domingo, Dominican Republic, 4 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 5 Srinagarind Hospital, Khon Kaen, Thailand, 6 Chiang Mai University, Chiang Mai, Thailand, 7 Krasnoyarsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases, Krasnoyarsk, Russian Federation, 8 Center for Prevention and Control of AIDS, Moscow, Russian Federation, 9 Ministry of Health, Saint-Petersburg, Russian Federation, 10 Mercer University, Macon, GA, USA, 11 Orlando Immunology Center, Orlando, FL, USA, 12 Gilead Sciences, Inc, Foster City, CA, USA Background: The unboosted integrase inhibitor containing single-tablet regimen (bictegravir/emtricitabine/tenofovir alafenamide, B/F/TAF) has shown efficacy and safety in HIV-1 infected patients. Bictegravir is a novel, unboosted INSTI that has been coformulated with F/TAF in an STR that has shown high rates of suppression with no resistance in phase 3 studies of treatment naïve patients. We now report Week 24 (W24) safety and efficacy of switching to B/F/TAF versus staying on baseline regimen (SBR) [elvitegravir (E)/cobicistat (C)/F/TAF, E/C/F/ tenofovir disoproxil fumarate (TDF) or atazanavir (ATV)+ritonavir (RTV)+F/TDF] in an all-women, international multi-centre, randomized, open-label, phase 3 trial. Methods: HIV-1 infected, virologically suppressed women on a protease inhibitor or boosted elvitegravir-containing regimen were randomized (1:1) to switch to B/F/TAF or stay on baseline regimen (SBR). The primary efficacy endpoint was the proportion of women with HIV1 RNA >50 copies (c)/mL at W48 with 4% noninferiority margin (FDA snapshot). A secondary efficacy endpoint of HIV-1 RNA <50 c/mL at W24 is reported here. Other secondary endpoints include safety (adverse events (AEs), laboratory abnormalities). This interimW24 efficacy and safety analysis was pre-specified. Results: We randomized and treated 470 women (234 B/F/TAF, 236 SBR (E/C/F/TAF n=125; E/C/F/TDF n=98; ATV+RTV+FTC/TDF n=13). Demographic and baseline characteristics were balanced; overall 37% black, 28.3%white, 21.7% Asian, median age was 39 years and CD4 count was 686 cells/μl. At W24 98.7% in the B/F/TAF group vs. 99.2% in the SBR group achieved HIV-1 RNA <50 c/mL (difference -0.4% (95%CI: 3.0% to 1.9%, p=0.68). Two participants, one in each group, had resistance testing; neither developed resistance to any study drug. No participant discontinued treatment due to an AE; there were no differences between groups in grade 3 or 4 treatment-emergent AEs (3.8% B/F/ TAF, 5.5% SBR group). Grade 3 or 4 laboratory abnormalities occurred in 17% of participants on B/F/TAF and 18% on SBR. Conclusion: At W24 women who switched to B/F/TAF maintained high levels of virologic suppression with comparable efficacy to those who remained on a

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