CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Conclusions: Lower CD4 count at baseline was associated with increased longitudinal rates of atrophy. This analysis represents the first large-scale, multi-site, longitudinal study of brain change in HIV and demonstrates the power of meta-analysis. HIV findings are often complicated by a host of factors including ART adherence/efficacy, substance abuse, comorbidities, and chronic inflammation. Pooling additional independent, heterogeneous study samples will further increase power to determine how various predictors of brain change generalize to the HIV epidemic.

384 Brain Volumetric Changes After 2 Years of ART Initiated During Acute HIV Infection Kalpana J. Kallianpur 1 ; Donn Colby 2 ; Neda Jahanshad 3 ; James L. Fletcher 2 ; Jintanat Ananworanich 4 ; Katherine Clifford 5 ; Khunthalee Benjapornpong 6 ; Collin Adams 5 ; Serena S. Spudich 7 ;VictorValcour 5 ; for the RV254/SEARCH010 Study Group 1 Univ of Hawaii, Honolulu, HI, USA; 2 SEARCH, Bangkok, Thailand; 3 Univ of Southern California, Los Angeles, CA, USA; 4 Military HIV Rsr Prog, Bethesda, MD, USA; 5 Univ of California San Francisco, San Francisco, CA, USA; 6 Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand; 7 Yale Univ Sch of Med, New Haven, CT, USA Background: Brain alterations (e.g., neuroinflammation, cortical atrophy, enlargement of brainstem) in the first year of HIV infection have been reported. However, little is known about whether changes in brain volumes may be detected over time in individuals on combination antiretroviral therapy (cART) initiated during acute HIV. Methods: We prospectively enrolled individuals in Bangkok who had acute HIV infection (Fiebig stages I-IV), on average 15 days after the estimated date of exposure. Participants underwent brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 1.5T and immediately thereafter initiated cART. MRI/MRS was repeated at regular intervals. Global and regional gray matter (GM) and white matter (WM) volumes at baseline and 24 months post-cART were obtained from T1-weighted MRI data by the FreeSurfer longitudinal processing stream. Wilcoxon signed-rank tests for related samples assessed changes from baseline to 24 months. For brain regions showing significant change, relationships between baseline metabolite concentration ratios over creatine (Cr) and 24-month volumes were examined by linear regression controlling for baseline volumes and patient age. Results: We evaluated 38 individuals (33 male) whose median (range) age was 29.0 (18-48) years, CD4 count 386 (132-1127) cells/mm 3 and plasma HIV RNA 5.54 (2.78-7.57) log 10 copies/mL at baseline prior to cART. Over the first 24 months of cART, volumetric decreases of 2%were found in caudate (p=0.002), putamen (p=0.00008) and pallidum (p=0.034), with a 1% decrease in total subcortical GM (p=0.002). Cerebellar GM and brainstem volumes increased by 5% (p=0.00003) and 1% (p=0.026), respectively. Clinical variables at baseline did not correlate with volumes at 24 months. Baseline N-acetylaspartate (NAA)/Cr in frontal GM predicted 24-month volumes of caudate (β=0.11, p=0.030) and putamen (β=0.15, p=0.016) independently of age and baseline volume. Pallidum volumes at 24 months were associated with baseline choline/Cr (β=0.19, p=0.018) in frontal WM. Conclusions: HIV patients demonstrated regional brain volumetric changes despite very early initiation of cART. Longitudinal studies of HIV-uninfected Thai individuals are needed to determine whether our observed atrophy rates are higher than those in healthy controls. Frontal neuronal injury during acute infection may predict basal ganglia atrophy. The cause and effect of cerebellar cortical enlargement are yet to be understood. 385 Regionally Specific Cortical Thinning in HIV+ Patients in the cART Era

Poster Abstracts

Ryan Sanford 1 ; Ana L. Fernandez Cruz 1 ; Lesley K. Fellows 1 ; Beau M. Ances 2 ; Louis Collins 1 1 McGill Univ, Montreal, QC, Canada; 2 Washington Univ in St. Louis, St. Louis, MO, USA

Background: HIV infection and its treatment affect the brain directly and indirectly, and can lead to cognitive impairment. Existing neuroimaging work has found evidence of brain volume loss in HIV+ patients, mainly in subcortical structures. However, the methods used to date may miss subtle cortical changes. Cortical extraction tools provide a sensitive measure of cortical thickness. In this cross-sectional study, we compared cortical thickness in HIV+ patients against healthy controls, and correlated it with measures of current and past viral suppression, and neuropsychological scores (NPZ-4). Methods: 133 HIV+ participants were recruited from a US Infectious Disease clinic, and 58 healthy controls (CTL) were recruited from the local community. All underwent T1-weighted brain magnetic resonance imaging and neuropsychological testing (Hopkins Learning Test-Revised, Digit-Symbol Modalities Test and Trail-Making Tests A&B). Cortical extraction captured the cortical surface and measured its thickness. Cortical thickness estimates were regressed on a vertex-wise basis against HIV status, nadir CD4+, current CD4+, viral load and NPZ-4. Results: The two groups were demographically similar (HIV+ age [mean ± SD]: 48 ± 12, nadir CD4+: 216 ± 200, current CD4+: 529 ± 314, 72% virologically suppressed; CTL age: 43 ± 12). HIV+ patients performed worse than controls on neuropsychological testing (NPZ-4: HIV+ -0.85 ± 1.27; CTL -0.14 ± 0.91, p<0.001). Significant cortical thinning was observed in specific brain regions in HIV+ patients compared to controls. The cortex was 0.2–0.4 mm thinner in the HIV+ group bilaterally in the lateral temporal and frontal lobes, as well as posterior cingulate and orbitofrontal cortex. Lower NPZ-4 scores were associated with thinner cortex in the left lateral temporal pole, left inferior occipital, right lateral occipital and right inferior lateral frontal cortices. There was no significant relationship between cortical thinning and measures of current or past viral suppression. Conclusions: Regionally specific cortical thinning was observed in this large sample of HIV+ patients, despite good current viral suppression in the majority. Cortical thinning was related to NPZ-4 scores, but was unrelated to systemic indicators of the severity of HIV infection. These findings show that even well-controlled infection has an impact on cortical thickness, and neuropsychological performance, perhaps related to central nervous system viral reservoirs, accelerated aging, or cART neurotoxicity.

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