CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

ml) and HIV-RNA in CSF at baseline was <20 copies/ml except 6pts (38;41;47;48;64;78 copies/ml). All pts had a negative serology for HBsAg and HCV. At baseline, the median genotypic susceptibility Charter score was 6 (3-8), with NRTI 90%, NNRTI 26%, PI 61%, II 36%; after T modification, the new score based on Charter+3 was 10 (≥9 in all pts except 1), with NRTI 84%, NNRTI 45%, PI 55%, II 97%, R5 inhibitor 32%. The average number of drugs in initial T was 3.1 [2-5] and 3.8 [3-5] after change. At week 48, significant improvements over baseline was observed (Wilcoxon exact Signed-Rank tests) on GDS (Global Deficit Score)(median 0.9 vs 1.4, p=0.03), with a GDS reduction for 55% of pts (17/31, 95%CI=[36.0%;72.7%]), number of altered cognitive domains (3 vs 4, p=0.02), and on Score of Cognitive Complaints (2 vs 4, p=0.0001). At baseline, according to the criteria of AAN, there were 7 ANI, 8 MND, and 16 HAD. At week 48, they became 12 ANI, 5 MND, 8 HAD and 6 pts with only one altered ability domain: the proportion of pts improving category of HAND was 15/31 (48.4%, 95%CI=[30.2%;66.9%]). Conclusions: In this little cohort of 31 pts with HAND, the gap of 48 weeks between tests prevents the learning effect. The treatment intensification by NNRTI, II, and/or R5 inhibitor was associated with a higher CHARTER score, leading to a statistically significant improvement in cognitive tests. 421 Statin or ACE/ARB Effects on Neurocognitive Function of HIV-Infected Adults Kristine M. Erlandson 1 ; Douglas Kitch 2 ; C.WilliamWester 3 ; Robert Kalayjian 4 ; EdgarT. Overton 5 ; Jose R. Castillo-Mancilla 1 ; Susan L. Koletar 6 ; Constance A. Benson 7 ; Kevin R. Robertson 8 ; Judith Lok 2 1 Univ of Colorado, Denver, CO, USA; 2 Harvard Sch of PH, Boston, MA, USA; 3 Vanderbilt Inst for Global Hlth, Nashville, TN, USA; 4 MetroHlth Med Cntr, Cleveland, OH, USA; 5 Univ of Alabama at Birmingham, Birmingham, AL, USA; 6 Ohio State Univ, Columbus, OH, USA; 7 Univ of California San Diego, San Diego, CA, USA; 8 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Background: Due to anti-inflammatory and anti-oxidant effects, we hypothesized that statins and angiotensin converting enzyme-inhibitors (ACE) or angiotensin-II receptor blockers (ARB) would protect neurocognitive function (NCF) among HIV+ adults on ART. Methods: Eligible participants from the ACTG ALLRT longitudinal cohort study were not on a statin or ACE/ ARB within 30 days of first neurologic assessment (baseline), and had assessments by NPZ-3 (z-score of averaged Trailmaking [Trails] A and B, and digit symbol test [DST] adjusted for race, language, education, age) from≥2 measurements, collected every 48 weeks. Persons with known impaired NCF, current/ prior CNS opportunistic infections, or major psychiatric illness were excluded; baseline diabetes also was excluded from ACE/ARB models. Marginal structural models estimated the causal effect of statin or ACE/ ARB initiation on NCF change; initial constant slope was assumed during the first year of treatment and a second constant slope thereafter. Demographics, CD4 count, HIV RNA, and cardiovascular risk factors were included as confounders of treatment. ACE/ARB was included as a confounder in statin models and statins as a confounder in ACE/ARB models. Results: 3949 (of 5972) ALLRT participants were included. At baseline, 53% of participants were <40 years old, male (82%), white (56%), non-smokers (62%), with CD4 count >200 cells/µL (79%) and HIV-1 RNA <400 copies/mL (73%). Statins were initiated in 611 (15.5%) and ACE/ARB in 377 (9.6%) participants; 182 participants (4.6%) received both. Overall, small increases in the mean NPZ-3 and component scores were seen (NPZ-3: 0.064 [95% CI: 0.059, 0.068]; Trails A: 0.079 [0.073, 0.085]; Trails B: 0.070 [0.065, 0.076]; DST 0.036 [0.031, 0.041]; all SD/year). Statin therapy was associated with a positive effect in Trails A during year 1 of exposure (Figure; estimate 0.09 [-0.01, 0.19] p=0.077) and a negative effect (-0.03 [-0.06, -0.01] p=0.007) with each subsequent year. Statins did not have a statistically significant effect on NPZ-3, Trails B, or DST. ACE/ARB had a negative effect on NPZ-3 scores (estimate -0.07 [-0.14, 0.01], p=0.078) and DST (-0.12 [-0.22,-0.02] p=0.023) during year 1 but not in subsequent years or on other neurologic function tests. Conclusions: Contrary to our hypothesis, statins and ACE/ARB were not associated with sustained neurocognitive improvement in HIV+ adults. The site of drug action (macro vs microvascular) or uncontrolled factors could account for the findings.

Poster Abstracts

422 Liver Fibrosis Linked to Cognition in HIV and HCV: TheWomen’s Interagency HIV Study Victor Valcour 1 ; Leah Rubin 2 ; Mary Obasi 1 ; Pauline Maki 2 ; MaryYoung 3 ;Wendy Mack 4 ; Mardge Cohen 5 ; Ada Adimora 6 ; PhyllisTien 1 ; for theWomen’s Interagency HIV Study Protocol Team 1 Univ of California San Francisco, San Francisco, CA, USA; 2 Univ of Illinois at Chicago, Chicago, IL, USA; 3 Georgetown Univ Med Cntr, Washington, DC, USA; 4 Univ of Southern California, Los Angeles, CA, USA; 5 John H. Stroger Jr. Hosp of Cook County and Rush Med Coll, Chicago, IL, USA; 6 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy (cART). Minimal Hepatic Encephalopathy (MHE) occurs in cirrhotic patients with or without HIV infection and is thought to be associated with inflammation. Since HIV impairs gut barriers to pathogens, we hypothesized that HIV-infected adults are vulnerable to MHE in the absence of cirrhosis. Methods: We completed a cross-sectional investigation of associations between liver fibrosis severity, using the aspartate aminotransferase to platelet ratio index (APRI), and neuropsychological testing performance in 1,479 women from the Women’s Interagency HIV Study (WIHS). A subset underwent liver transient elastography (n=303). We evaluated associations to neuropsychological testing performance on a one-hour testing battery. Results: We evaluated 1479 women (mean (SD) age of 46 (9.3) years): 770 (52%) only HIV-infected, 73 (5%) only HCV-infected, 235 (16%) HIV and HCV co-infected and 401 (27%) HIV- and HCV uninfected. 1221 (83%) had an APRI ≤0·5 (no or only mild fibrosis), 206 (14%) had an APRI >0·5 and ≤1·5 (moderate fibrosis) and 52 (3%) had an APRI >1·5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with deficits in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). Similarly, the severity of fibrosis, measured by liver transient elastography, was associated with deficits in attention, executive functioning, and fluency. Conclusions: Independent of HCV and HIV, liver fibrosis has distinct contributions to cognitive performance in the era of cART. In adjusted models, HCV and HIV had only limited associations when fibrosis is included. These data highlight the heterogeneous contributions to cognitive impairment in the era of combination antiretroviral therapy. 423LB A Randomised Controlled Trial of Maraviroc-Intensified bPI ART on Cognitive Function AlanWinston 1 ; George Bouliotis 2 ; Ranjababu Kulasegaram 3 ; Amanda Clarke 4 ; Frank A. Post 5 ; Mark Nelson 6 ; Laura Burgess 2 ; Borja Mora-Peris 2 ; SteveTaylor 7 ; Deborah Ashby 2 1 Imperial Coll of Sci, Tech and Med, London, UK; 2 Imperial College London, London, UK; 3 St. Thomas’ Hosp, London, UK; 4 Brighton and Sussex Hosps NHS Trust, Brighton, UK; 5 King’s Coll Hosp NHS Fndn Trust, London, UK; 6 Chelsea and Westminster Hosp NHS Fndn Trust, London, UK; 7 Birmingham Heartlands Hosp, Birmingham, UK Background: Maraviroc-intensified ART may have anti neuroinflammatory properties which could result in cognitive benefits. However intensified ART may be associated with increased neurotoxicity.

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