CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

1 Hosp Univ La Paz, Madrid, Spain, Spain, 2 Instituto de Salud Carlos III, Madrid, Spain, 3 Univ Rey Juan Carlos, Alcorcón, Spain Background: Implications of ART neuropenetration (NP) on brain function (BF) of HIV patients starting therapy are uncertain.

Methods: Randomized, pilot, open-label, 24-week trial designed to evaluate the effects on BF of starting ART with different NP: ABC/3TC+EFV (high NP) vs. TDF/FTC+ATV/r (low NP). In addition to conventional virological and immunological endpoints, at baseline and week 24, we determined creatinine (Cr) ratios of N-acetyl-aspartate (NAA/Cr), Choline (CHO/Cr) and Mioinositol (MI/Cr) in the frontal lobe (FL), basal ganglia and parietal lobe using 3T Magnetic Resonance Spectroscopy of the brain. Cognition was evaluated with a 7-domain battery of tests. ART type effect on brain metabolite ratios and cognitive changes were determined using linear regression models adjusted by baseline levels. Results: 25 patients were included: 14 on ABC/3TC+EFV and 11 TDF/FTC+ATV/r. Baseline characteristics were similar in both groups (table). 1 patient on ABC/3TC+EFV was discontinued at week 5 due to severe pneumonia. At week 24, 21 patients achieved HIV suppression (HIV RNA <50 cop/mL) (11 on ABC/3TC+EFV and 10 on TDF/FTC+ATV/r), 19 still on randomized ART and 2 on other regimens (1 per group). By ITT, CHO/Cr and MI/Cr increased with ABC/3TC+EFV (0.073±0.091 and 0.0716±0.223) and decreased with TDF/ FTC+ATV/r (-0.034±0.119 and -0.013±0.098) in the white matter of FL (p=0.034 and p=0.088 respectively) and MI/Cr also tended to increase with ABC/3TC+EFV (0.065±0.096) and to decrease with TDF/FTC+ATV/r (-0.003±0.069) in the grey matter of FL (p=0.084). No significant changes of NAA/Cr were observed. Global cognition (NPZ-7 change) slightly improved in both groups (0.28±0.35 vs. 0.21±0.27; p=0.32). By cognitive domains, delayed recall improved with ABC/3TC+EFV (0.31±0.58) and decreased with TDF/FTC+ATV/r (-0.11±0.4) (p=0.01). Learning tended to improve more with ABC/3TC+EFV (0.37±0.79 vs. 0.22±0.63; p=0.085). No other differences were observed in cognitive domains. Conclusion: Starting ART with high NP as ABC/3TC+EFV vs. starting ART with low NP as TDF/FTC+ATV/r was associated with higher levels of the inflammatory marker CHO/Cr in the FL and had positive effects on delayed recall tasks.

Poster and Themed Discussion Abstracts

401 RESTING CEREBRAL BLOOD FLOW AND RISKY DECISION-MAKING IN HIV+ AND HIV– YOUNG ADULTS Robert S. Smith 1 , Anika Guha 2 , Aaron Tanenbaum 1 , Florin Vaida 3 , Robert Paul 4 , Beau M. Ances 1 1 Washington Univ in Saint Louis, Saint Louis, MO, USA, 2 Univ of California Los Angeles, Los Angeles, CA, USA, 3 Univ of California San Diego, San Diego, USA, 4 Univ of Missouri–St. Louis, St. Louis, MO, USA Background: Few studies have investigated neuroimaging signatures of risky decision-making in HIV+ young adults. HIV-infected (HIV+) individuals often engage in high-risk behavior. Brain regions involved in executive function mature during adolescence. Many of the same regions experience reduced blood flow in the presence of HIV infection. In response to blood flow deficits, HIV+ individuals may recruit additional regions in task experiments. We studied the relationship between resting state cerebral blood flow (rCBF) and risky decision-making in HIV+ (n=41) and HIV-uninfected (HIV–) (n=62) participants. Methods: Risky decision-making, measured via the Iowa Gambling Task (IGT), was compared voxel-wise to rCBF, acquired via pseudocontinuous arterial spin labeling. Separate rCBF-IGT relationship maps were obtained for HIV– and HIV+ participants, and for the combination of HIV– and HIV+ participants. Relationship maps comprise voxels with a significant (p<0.05) rCBF-IGT relationship that are apart of clusters larger than chance (p<0.05). The three maps were evaluated for (un)shared regions. For HIV+ individuals, rCBF was compared to HIV disease factors (recent and nadir CD4, and current viral load). All comparisons were made via Pearson correlation. Results: HIV+ participants performed worse on the IGT compared to HIV– controls. We observed three spatially distinct regions (Figure 1a), Regions-I, -II, and -III, that defined a decreasing rCBF-IGT relationship in HIV+, which is reversed in HIV– (Figure 1b). Region-I (red), strongest rCBF-IGT link in HIV+ (r=0.51), was comprised of frontal and insular areas. Region-II (yellow) contained middle frontal, insular, and orbitofrontal regions. Region-III (blue), strongest rCBF-IGT link in HIV– (r=0.54), consisted of dorsolateral prefrontal and posterior cingulate areas. We quantified rCBF changes associated with the transition to Region-I from -III and found: HIV+ had significantly reduced rCBF in Region-III compared to HIV- controls, rCBF in Regions-III and -I were negatively associated (r=-0.34) in HIV+, and the difference in Region-I and -III rCBF negatively associated with recent CD4 (r=-0.35). Conclusion: HIV+ young adults recruited additional executive areas at rest in response to blood flow deficits. Increased CD4 counts may lead to partial blood flow recovery, but may not reinstate functionality in retracted territory. Longitudinal studies are needed to determine whether recovery translates to reduced high-risk behavior at this critical development time.

CROI 2017 163