| Publication Abstract Display | | Type: Published Abstract | | Title: Compartmentalized HIV DNA populations persist in CSF despite suppressive ART. | | Authors: de Oliveria MF, Chaillon A, Letendre S, Strain M, Ellis R, Morris S, Little S, Smith DM, Gianella S | | Year: 2016 | | Publication: Annual Conference on Retroviruses and Opportunistic Infections | | Volume: Issue: Pages: | | Abstract:Persistence of HIV DNA in the central nervous system likely contributes to inflammation, brain damage and neurocognitive (NC) impairment during antiretroviral therapy (ART). The effects of early ART initiation on these parameters are still unknown.
Paired blood and 40 mL cerebrospinal fluid (CSF) samples were collected from 16 HIV+ individuals on suppressive ART (<50 copies/ml): 9 subjects started ART ≤4 months from estimated date of infection (EDI) and 7 started ART >14 months from EDI. NC functioning was measured by Global Deficit Score (GDS). HIV DNA levels were measured in peripheral blood mononuclear cells (PBMC) and CSF cells by droplet digital PCR; soluble inflammatory markers (sCD163, IL-6, MCP-1, TNF-α) and marker of neuronal damage (neurofilament chain [NFL]) were measured in blood plasma and CSF supernatant by immunoassays. Next generation sequencing (NGS) data by Roche 454 were successfully generated for HIV env from 8 paired blood and CSF cell pellets (3 with early and 5 with late ART). Viral compartmentalization analysis via Fst statistics was performed using NGS data and repeated using representative haplotypes to guard against possible skewing of allelic frequencies due to PCR amplification and other biases. Cross-sectional comparisons between groups (early versus later ART) were performed using non-parametric statistical analysis.
In these suppressed HIV+ individuals (median duration on ART: 2.6 years), HIV DNA was detected in 62.5% (10/16) of CSF cell pellets and 93.8% (15/16) of PBMCs. Early initiation of ART was associated with lower CSF levels of IL-6 (p=0.03) and TNF-α (p=0.02), but no difference in GDS, NFL, or HIV DNA as compared to later ART group. Significant compartmentalization of HIV DNA populations between blood and CSF were detected in 7 out of 8 subjects, and these findings were congruent between the two approaches mentioned above. Phylogenetic analysis confirmed presence of monophyletic HIV DNA populations within the CSF for each participant (aLRT > 0.9), and their persistence over time in the two participants with longitudinal sampling (2 and 5 months between time points).
A compartmentalized HIV DNA population in CSF was detectable in the majority of HIV+ individuals despite long-term suppressive ART and even when ART was started during early HIV-infection. Also, early ART start was associated with lower inflammation in CSF (IL-6 and TNF-α), but no difference in GDS compared to later start of ART. |
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