CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: The meta-analysis (primary analysis) shows the risk of NPAE in TN patients was similar for INSTI vs EFV and INSTI vs PI. Risk difference (95% CI) for DSS AEs and PPD AEs: INSTI vs EFV -3% (-5,0) and -1% (-2,1) and INSTI vs PI -1% (-2,4) and 0% (-2,1). Results were identical for the fixed and random effects analyses. Grade 3 and 4 events occurred in 1% of INSTI and PI subjects and 2% of EFV. Subgroup analyses were not interpretable due to small sample size. Conclusion: This meta-analysis shows the risk of NPAE when analyzed at the level of pooled DSS and PPD SMQs is similar for INSTIs vs EFV, with a trend toward lower risk with INSTIs compared with EFV. The risk for NPAEs is similar between INSTIs and PIs. Although NPAEs were infrequent and risk was not increased with INSTIs, providers should be aware of the association between HIV infection, ART, and NPAEs.

Poster and Themed Discussion Abstracts

373

PROGRESSIVE HIPPOCAMPAL NEURONAL LOSS IN PEDIATRIC SIV INFECTION Heather Carryl 1 , Koen Van Rompay 2 , Kristina De Paris 3 , Mark W. Burke 1 1 Howard Univ, Washington, DC, USA, 2 Univ of California Davis, Davis, CA, USA, 3 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Background: As of 2013, there are 3.2 million children under the age of 15 living with HIV, globally, with an estimated one new diagnosis every 2 minutes. The devastating neurological impact of HIV on children includes loss of brain growth, motor abnormalities and cognitive dysfunction. Despite early antiretroviral treatment (ART) intervention to suppress viral load, neurological consequences of perinatal HIV-1 infection persist. Utilizing the pediatric simian immunodeficiency virus (SIV) infection model, we tested the hypothesis that early life SIV infection depletes neuronal population in the hippocampus. Methods: A total of 22 infant rhesus macaques (Macaca mulatta) were divided into three groups: Group 1 received intravenous inoculation of SIVmac251 on postnatal day 3 (n=3) with a survival time of 6-10 weeks; Group 2 was orally challenged with SIVmac251 at week 9 of age (n=15) with a survival period of 12 weeks post-infection; and Group 3 served as uninfected controls with a survival time of 15-22 weeks. Systematic sections through the hippocampus regions CA1 to CA3 were Nissl stained and hippocampal pyramidal neurons were quantified using design-based stereology. Results: We have previously reported that intravenously SIV-infected neonatal infant macaques (Group 1) displayed a 42% neuronal reduction throughout the hippocampal CA fields. The orally infected infant macaques in Group 2 displayed a 75% neuronal reduction in the CA1 compared to controls and 54% fewer neurons than Group 1 infants. The CA2 region showed a similar pattern with a 67% reduction between Group 2 and controls and a 40% difference between Group 1 and 2. In the CA3 region there were no significant differences between Groups 1 and 2, however both SIV-infected groups had significantly fewer pyramidal neurons than control subjects. Volume differences were found only in the CA1 region between the three groups. Plasma viral load ranged from 170,000 to 650,000,000 copies/ml plasma vRNA, however there were no correlation between plasma viral load and neuronal populations in any of the CA fields. Conclusion: The loss of hippocampal neurons may contribute to the rapid neurocognitive decline associated with pediatric HIV infection. While each subfield showed vulnerability to SIV infection, the CA1 and CA2 subregions demonstrated a potentially enhanced vulnerability to perinatal SIV infection. These data underscore the need for early diagnosis and treatment including therapeutics targeting the CNS. 374 HIV GENE VARIANTS ALTERING CORECEPTOR BINDING & DRUG RESISTANCE PREDICT CNS PHENOTYPES Debashis Sahoo, Sarah Dabydeen , Kumud K. Singh Univ of California San Diego, La Jolla, CA, USA Background: Independently evolved HIV subspecies develop gene variants that provide selective advantage to viral survival and pathogenicity. We hypothesized that unique variants in HIV envelope gp120 (Env) and reverse transcriptase (RT) gene sequences from brain may predict HIV related central nervous system (CNS) disease phenotypes. Methods: Publicly available database (HANDDB, handdatabase.org) with 5,783 non-redundant HIV subtype B sequences (n=163) from brain and non-brain tissues was assessed for HIV associated neurocognitive disorders (HAND). After aligning sequences by clustalw algorithm, we identified unique nucleotide variants and determined their association with the CNS phenotypes. Results: Using commonly used HIV genome HXB2 sequence as a reference, we found that specific variants at Env 7144T nucleotide position or amino acid position 307 (aa307, Ile) were associated with HAND phenotype (97% of HAND, n=1016 vs. none in non-HAND sequences, n=661; p < 0.001). Also, position 6979G (aa252, Arg) had similar association (76% of HAND, n=816 vs. 17% in non-HAND sequences, n=590; p < 0.001). These variants were common in brain and CSF, present predominantly in males, and were associated with lower CD4 cell count, HIV associated dementia/ AIDS dementia complex, and minor cognitive motor disorder. For RT gene, 2754A (aa224, Thr) was predictive of HAND phenotype

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