CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

1 Fundació Lluita Contra la Sida, Badalona, Spain, 2 Institut d’Investigació Biomèdica de Bellvitge, Barcelona, Spain, 3 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 4 Consorci Sanitari Terrassa Hospital, Barcelona, Spain, 5 Institut de Diagnòstic per la Imatge, Badalona, Spain, 6 Projecte dels NOMS-Hispanosida, Barcelona, Spain Background: Data about the possible CNS toxicity of integrase strand transfer inhibitors (INSTI) in people living with HIV (PLWH) are growing. We investigated this in the ARBRE Study, an observational trial that assessed the impact of antiretroviral therapy with INSTI on brain outcomes according to the time of therapy initiation. Methods: The ARBRE Study included 3 study arms: early-treated PLWH (G1: <3 months since estimated date of infection, n=12), chronically treated (G2: >6 months, n=15), and matched seronegative controls (G3, n=15). Both HIV+ groups were treated with an INSTI-containing regimen (dolutegravir, elvitegravir, raltegravir). Assessments were performed at baseline (prior to therapy initiation), week 4, and week 48, and evaluated cognitive functioning (6 domains, NPZ12), 3T magnetic resonance imaging (voxel-wise whole-brain structural changes), and functional outcomes (daily functioning, adverse events, and emotional symptoms). Study endpoints were based on difference in change at week 48 among arms. Results: Baseline cognitive functioning and neuroimaging parameters were comparable among groups. Regarding functional outcomes, daily functioning and CNS adverse events were also comparable, although participants in G1 had more depressive symptoms (p=0.03), anxiety (p=0.04), and perceived stress (p=0.03) than the other groups. At week 4, no significant changes were observed in cognitive functioning or functional outcomes. Neuroimaging analyses detected a significantly more reduced gray matter volume in the medial orbitofrontal cortex in G2 (p=0.005). At week 48, cognitive performance did not significantly improve or differ between groups (p=0.14). The decreased medial orbitofrontal volume found in G2 persisted, although to a lesser extent (p=0.04). Emotional symptoms improved significantly in G1, reaching comparable levels among groups (p>0.10). Conclusion: Cognitive outcomes were similar between PLWH initiating therapy with INSTI during early infection or later than 6 months after HIV transmission. However, participants who initiated therapy later had more reduced gray matter volume that persisted for 48 weeks, which is consistent with prior reported data showing cortical thickness abnormalities in virally suppressed HIV+ patients. An extended follow-up is required to ascertain the future progression of CNS outcomes in PLWH on therapy with INSTI. 440 NEUROPSYCHIATRIC OUTCOMES BEFORE AND AFTER SWITCHING TO DOLUTEGRAVIR-BASED THERAPY Phillip Chan 1 , Orlanda Goh 1 , Eugène Kroon 1 , Donn J. Colby 1 , Carlo Sacdalan 1 , Suteeraporn Pinyakorn 2 , Somporn Tipsuk 1 , Nittaya Phanuphak 1 , Praphan Phanunphak 3 , Jintanat Ananworanich 2 , Victor Valcour 4 , Serena S. Spudich 5 , Robert Paul 6 , for the RV254/SEARCH010 1 SEARCH, Bangkok, Thailand, 2 US Military HIV Research Program, Bethesda, MD, USA, 3 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 4 University of California San Francisco, San Francisco, CA, USA, 5 Yale University, New Haven, CT, USA, 6 University of Missouri St Louis, St Louis, MO, USA Background: Dolutegravir (DTG) is a 2nd generation HIV integrase inhibitor currently recommended as 1st-line antiretroviral therapy (ART). Neuropsychiatric (NP) adverse events have been reported with DTG but NP symptoms have not been systemically quantified using structured scales. This study examined mood and cognitive parameters before and after a planned transition from a non-DTG to a DTG-based regimen within a longitudinal study. Methods: Participants on ≥ 24 weeks of ART started in acute HIV infection (AHI) underwent NP assessments before and after transition to DTG. They underwent: 1) Patient Health Questionnaire-9 (PHQ-9), a 9-item survey (score range 0-27) that evaluates both somatic and affective/cognitive symptoms of depression; 2) a 2-Questions screening that has been validated locally for major depression; 3) Distress Thermometer for anxiety/stress (scores 0-10); and 4) a 4-test battery that included Color Trails 1 and 2, Trails Making A and non-dominant hand grooved pegboard test. Outcomes before and after DTG were compared by McNemar and Wilcoxon signed-rank tests; multivariate linear regression examined factors that were correlated with the change of PHQ-9 scores. Results: 256 individuals (95%male, median age 30 [IQR 25-36]) switched to DTG-based ART after a median 144 [IQR 24-192] weeks of ART (82% efavirenz- based) initiated in AHI. Serial assessments were done at median 19 [IQR 8-35]

438 CENTRAL NERVOUS SYSTEM SAFETY OF A KICK-AND-KILL STRATEGY WITH ROMIDEPSIN Sara Carrillo-Molina 1 , Ignacio Martínez-Zalacaín 2 , Beatriz Mothe 3 , José Moltó 1 , Christian Manzardo 4 , Jose M. Miro 4 , Josep Coll 3 , Michael Meulbroek 5 , Anna Prats 1 , Maite Garolera 6 , Tomas Hanke 7 , Christian Brander 3 , Carles Soriano- Mas 2 , Jose A. Muñoz-Moreno 1 , for the BCN02-Neuro Substudy Group 1 Fundació Lluita Contra la Sida, Badalona, Spain, 2 Institut d’Investigació Biomèdica de Bellvitge, Barcelona, Spain, 3 IrsiCaixa Institute for AIDS Research, Badalona, Spain, 4 Hospital Clinic of Barcelona, Barcelona, Spain, 5 Projecte dels NOMS- Hispanosida, Barcelona, Spain, 6 Consorci Sanitari Terrassa Hospital, Barcelona, Spain, 7 The Jenner Institute, Oxford, UK Background: Romidepsin (RMD) is a histone deacetylase inhibitor (HDACi) able to induce HIV transcription in vitro and in vivo. Its effects on the brain during cure strategies are unknown. We investigated cognitive, neuroimaging, and functional outcomes in the BCN02-Romi Study, a trial that assessed the effects of an HIVconsv vaccine in combination with RMD in early-treated HIV-infected persons (clinicaltrials.gov: NCT02616874). Methods: The BCN02-Romi Study tested a kick&kill strategy that combined 2 administrations of an HIVconsv vaccine (pre and post RMD, weeks 0 and 9), with 3 weekly infusions of RMD (5mg/m2; weeks 3, 4, and 5), a monitored antiretroviral pause (MAP, starting at week 17), and a 24-week period after the reinitiation of cART. Inclusion in the BCN02-Neuro Substudy was offered to the 15 individuals recruited in the BCN02-Romi Study and 11 accepted to participate (Intervention Group, IG, n=11). Early-treated but not vaccinated individuals were recruited as controls (Control Group, CG, n=10). CNS assessments were performed before RMD administration (Pre), after final RMD administration (Post), and after MAP + 24-week cART reinitiation (Final). Study variables comprised cognitive functioning (NPZ6), 3T magnetic resonance imaging (voxel-wise whole-brain structural changes), and functional outcomes (daily functioning, adverse events, and emotional symptoms). Study endpoints were based on between-arm differences in change from Pre to Post and Final assessments. Results: Global cognitive functioning was comparable between groups at the 3 study timepoints (mean NPZ6 [SD]): Pre: IG: 0.28 (0.64), CG: 0.28 (0.63), p=0.98; Post: IG: 0.42 (0.54), CG: 0.31 (0.61), p=0.66; Final: IG: 0.41 (0.59), CG: 0.55 (0.76), p=0.69. Analysis of change confirmed these results (mean NPZ6 change [SD]): Post: IG: 0.13 (0.31), CG: 0.03 (0.32), p=0.45; Final: IG: 0.15 (0.43), CG: 0.27 (0.35), p=0.56. Neuroimaging analyses did not find differences between groups at any timepoint (all p values >0.10). No differences were also observed in daily functioning outcomes, CNS adverse events, or emotional symptoms. Conclusion: No detrimental effects of a kick&kill strategy with RMD were observed on cognitive functioning, neuroimaging, or functional outcomes in this small study. The HIV cure approach investigated, including the use of an HIVconsv vaccine, administration of RMD, and cART interruption with posterior 24-week therapy reinitiation, appears to be safe for the brain. 439 CENTRAL NERVOUS SYSTEM EFFECTS OF THERAPY INITIATION WITH INTEGRASE INHIBITORS Anna Prats 1 , Ignacio Martínez-Zalacaín 2 , Beatriz Mothe 3 , Eugènia Negredo 1 , Maite Garolera 4 , Sira Domènech-Puigcerver 5 , Michael Meulbroek 6 , Carmina R.Fumaz 1 , Maria J. Ferrer 1 , Bonaventura Clotet 3 , Carles Soriano-Mas 2 , Jose A. Muñoz-Moreno 1 , for the ARBRE Study Group

Poster Abstracts

CROI 2019 159