Neurocognition during Virologically Suppressive ART Michelli F Oliveira 1 Masato Nakazawa 1 Andrej Vitomirov 1 Mitchell Zhao 1 Ben Gouaux 1 David Moore 1 Ron Ellis 1 ID: 614890
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HIV Reservoirs in the Brain and its Association with Sex and Neurocognition during Virologically Suppressive ART
Michelli F. Oliveira1, Masato Nakazawa1, Andrej Vitomirov1, Mitchell Zhao1, Ben Gouaux1, David Moore1, Ron Ellis1, Davey Smith1,2, Sara Gianella1
Abstract #: MOPDA0103
No Conflicts of Interest to declare.
Thank you to all the study participants!Slide2
Approach63 virologically
suppressed HIV-infected cases from the National NeuroAids Tissue Consortium: 12 women and 51 men.Neurocognitive (NC) functioning: t-scores (7 neuropsychological abilities) at last visit (3 months before death).Paired Post-mortem: [i] frontal (FC) [ii] occipital cortex (OCC) [iii] basal ganglia (BG) [iv] peripheral lymph tissues (lymph node or spleen).Levels of HIV DNA (gag and 2-LTR) by ddPCR, normalized for cells input (rpp30).OUR GOALSCompare
HIV DNA levels in post-mortem brain tissues from ART suppressed HIV-infected women and men.
Evaluate its association with pre-mortem neurocognitive functioning.Slide3
Results
HIV gag: majority of brains (65%) and all lymph tissues; 2-LTR: 21% of brains and 54% of lymph tissues.Lymph tissue had higher levels of HIV DNA than brain tissues (p<0.01), but did not predict the levels in brain tissues (p=0.7
).BG and FC had similar levels of HIV DNA (p>0.2); OCC had lower levels
than the other brain regions (p=0.01).
Women had higher levels of HIV DNA in tissues (gag: p=0.03; 2-LTR, p=0.05).None of the tested covariates (age, EDI, time on ART, most recent CD4, race, study site) were associated with HIV DNA levels (all p>0.1).Slide4
Results
Levels of HIV gag in OCC were associated with worse NC functioning (p=0.04) in both sexes; 2-LTR levels were not associated with NC functioning (p>0.2).Sex-differences in NC functioning were observed in Motor and Speed of Information processing sub-domains, with women having better functioning (p<0.05), regardless of HIV gag levels.Slide5Slide6
Conclusions
Our study shows a differential distribution of HIV reservoirs in the brain.Lymph tissues HIV DNA levels do not predict the levels in brain, suggesting that HIV persistence in brain tissue might be driven by different mechanisms.Higher levels of HIV reservoir in women may be due to higher HIV replication in tissues (measured by levels of 2-LTR).Levels of HIV DNA in OCC poorer global NC functioning and the motor sub-domain.
Future studies including larger cohorts, especially with an increased number of women are needed to confirm our findings