CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

448 Efavirenz Use is Not Associated with Increased Risk of Neuropsychological Impairment Sean B. Rourke 1 ; John Gill 2 ; Anita Rachlis 1 ; Colin Kovacs 4 ; Gordon Arbess 5 ; Jason Brunetta 4 ; Adriana Carvalhal 1 ; Chris Power 2 ; Ann N. Burchell 3 ;Tsegaye Bekele 3 1 University of Toronto, Toronto, Canada; 2 University of Alberta, Calgary, Canada; 3 The Ontario HIV Treatment Network, Toronto, Canada; 4 Maple Leaf Medical Clinic, Toronto, Canada; 5 St. Michael’s Hospital, Toronto, Canada Background: Efavirenz is known to increase neuropsychiatric symptoms shortly after initiation of therapy, and while these generally resolve within 2-3 months, the evidence on whether there is an increased risk of neuropsychological impairment (NPI) which persist is mixed. The purpose of this study is to examine whether people living with HIV who are on cART that includes Efavirenz have higher risk of NPI. Methods: Study participants were HIV patients on cART from two outpatient clinics in Toronto, Canada. Neuropsychological assessment was done every 12 months (median follow-up time: 24.5 months) using a brief test battery that included Hopkins Verbal Learning Test- Revised (HVLT-R), Grooved Pegboard, and WAIS-R Digit Symbol tests. Demographically corrected T-scores and Global Deficit Score were computed. NPI was defined using a Global Deficit Score of 0.5 or greater. We estimated the odds of NPI using Generalized Estimating Equations adjusting for baseline and time-dependent covariates. Results: 831 adults (80%men, 62% Caucasian, 84%with undetectable HIV viral load) with 2,160 observations were included. Nearly one-third (n=266, 32%) were on Efavirenz, 234 (28%) had used Efavirenz in the past, and 331 (40%) were Efavirenz naïve. Prevalence of NPI was slightly higher among those who were Efvairenz naïve (63%) than those who had been on Efavirenz in the past (57%) or those who are on Efavirenz currently (56%) at baseline. In unadjusted logistic regression analysis, current Efavirenz use was associated with significantly lower odds of NPI (OR=0.72; 95% CI: 0.53-0.97; p=0.033), while past use of Efavirenz showed no association (OR=0.76; 95% CI: 0.56-1.03, p=0.079). In multivariate logistic regression, however, the association between current Efavirenz use and NPI was no longer significant (OR= 0.77; 95% CI: 0.57 to 1.05; p=0.099). Among the covariates examined, nadir CD4 count <200 cells/mm 3 (OR=1.40; 95% CI: 1.047-1.84; p=0.016), Hepatitis C infection (OR= 1.58; 95% CI: 1.06-2.35; p=0.002), and diabetes (OR=2.32, 95% CI: 1.30-4.16; p=0.005) were associated with higher odds of NPI. Conclusions: Current or past use of Efavirenz is not associated with an increased risk of neuropsychological impairment in our Ontario sample which replicates the findings of Antinori et al (2014) in a Canadian sample. 449 Quantitative Electroencephalogram as a Translational Biomarker for NNRTI CNS AEs PamelaTannenbaum; Jacquelyn Binns; SpencerTye; Alan Savitz; Steven Fox; Christopher Burgey; Ming-tain Lai; Arthur Simen; daria hazuda; Michael D. Miller Merck and Co, Inc, West Point, PA, US Background: Although it is an effective drug for treating HIV-1 infection, the non-nucleoside RT inhibitor (NNRTI) efavirenz (EFV) elicits significant CNS adverse events (AEs) such as insomnia, headache, nausea, dizziness, cognitive impairment and depression. Currently marketed NNRTIs vary in efficacy and have varying degrees of CNS AEs. Therefore, an NNRTI with high efficacy and low potential for CNS toxicities is still needed to maximize the utility of the class. Methods: Freely-moving rats (n=16) and monkeys (n=12) were implanted with telemeterized EEG, electromyography and electrooculogram transmitters and recorded 24hr/day. In a within-subjects cross over design, animals were dosed with 50-200mg/kg EFV (BID, PO) or vehicle for 14 days each. Recordings were analyzed for sleep/wake and qEEG spectral frequency changes. Spectral differences were also compared to our EEG data collected previously on healthy volunteers receiving EFV (600mg QD) with cognitive impairment (Simen et al, J Sleep Res 2014). Results: In both rats and monkeys, EFV produced sedation and a significant dose-responsive qEEG signature of increased low-frequency bands (Theta-Alpha) with decreased mid- frequency bands (Sigma-Beta). This signal appeared within 1-2 days of initial exposure and diminished across the first week of treatment. Our previous healthy volunteer EFV EEG study produced a strikingly similar increase in Theta-Alpha plus decrease in Sigma-Beta qEEG signature with EFV. Conclusions: A highly conserved EFV qEEG signature between rats, monkeys and humans makes this novel translational qEEG biomarker potentially useful for rapidly assessing the likelihood of CNS AEs in NNRTI drug development. The animal qEEG signal strength appeared to parallel the time course of reported clinical CNS AEs. Clinical studies of new NNRTIs may benefit from using qEEG to identify CNS adverse effect risk. 450 Neurocognition Following Antiretroviral Initiation in Behaviorally HIV-Infected Youth Sharon Nichols 1 ; Patricia Garvie 2 ;Tiandong Li 3 ;Weijia Ren 3 ; Bill Kapogiannis 4 ; Bret Rudy 5 ; John Sleasman 6 ; StevenWoods 7 ; Ana Puga 2 The Adolescent MedicineTrials Network for HIV/AIDS Interventions 1 University of California San Diego, La Jolla, CA, US; 2 Children’s Diagnostic & Treament Center, Inc., Ft. Lauderdale, FL, US; 3 Westat, Inc., Rockville, MD, US; 4 National Institutes of Health (NIH), Bethesda, MD, US; 5 New York University, New York, NY, US; 6 Duke University, Durham, NC, US; 7 University of California, San Diego, La Jolla, CA, US Background: Evidence suggests adolescents and young adults (youth) living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments. However, the role of HIV in these impairments and their potential to improve with antiretroviral therapy (ART) are unclear. The purpose of this study was to examine the impact of ART initiation and its timing on neurocognitive functioning in YLWH. Methods: Data are from a prospective observational study supported by the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH ages 18-24 at entry completed baseline and four additional assessments of attention/working memory, complex executive functioning, and motor functioning over three years. Group 1, co-enrolled in early ART initiation study, initiated ART at enrollment CD4>350 (n=56); Group 2 had CD4>350 and were not initiating ART (n=66); and Group 3 initiated ART with CD4<350 (n=59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted Protease Inhibitor monotherapy at 48 weeks for those in Group 1 with suppressed viral load (n=35). Analyses used hierarchical linear modeling. Covariates included demographic, behavioral, and medical history variables. Results: Participants were predominantly male (80.7%), non-Hispanic Black/African-American (65.2%) or Hispanic (22.7%), self-identified as gay or bisexual (71.2%), and high school educated or beyond (72.3%), with 40.8% currently in school. All groups showed improved performance over time with peak at 96 weeks in all three functional domains (e.g., see Figure for change in Motor scale by group over time). Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. Baseline cognitive functioning predicted change in some domains but did not interact with treatment.

Poster Abstracts

311

CROI 2015