Evaluation of archival HIV DNA in brain and lymphoid tissues

HIV reservoirs persist in anatomic compartments despite antiretroviral therapy (ART). Characterizing HIV reservoirs in central nervous system (CNS) and other tissues is crucial to inform cure strategies. We evaluated paired autopsy brain – frontal cortex (FC), occipital cortex (OCC), basal ganglia (BG) – and peripheral lymphoid tissues from 63 people with HIV. Participants passed away while virally suppressed on ART and without evidence of CNS opportunistic disease. We quantified HIV DNA and, from a subset of 14 participants, we obtained full-length HIV-envelope (FL HIV-env) sequences. We detected HIV DNA (gag) in most brain (65.1%) and all lymphoid tissues. Lymphoid tissues had higher HIV DNA levels compared to brain (p<0.01). Levels of HIV gag between BG and FC were similar (p>0.2), while OCC had the lowest levels (p=0.01). Females had higher HIV DNA levels in tissues than males (gag: p=0.03; 2-LTR, p=0.05), suggesting possible sex-associated mechanisms for HIV reservoir persist..., To evaluate genetic composition and relationships of HIV provirus, we performed single-genome amplification (SGA) coupled with PacBio sequencing to obtain full-length (FL) HIV envelope sequences across 14 participants and the following tissues:
- Frontal cortex (FC, n= 9)
- Occipital cortex (OCC, n= 5)
- lymph node (LN, n= 5)
- Spleen (SP, n= 8),