Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy

Abstract

Objective: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). Design: IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. Methods: Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) more than 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIVpol/gag-DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. Results: Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. Nine of 18 (50%) were female sex-at-birth, and 14 of 18 (78%) were black. Median (range) age was 20 years (13–27), time on ART was 18.3 years (8.0–25.5), and FCCS was 68 (53–80). HIV-DNA was detected in PBMCs from all participants. In CSF, two of 18 (11%, 95% CI: 1.4–34.7%) participants had detectable cell-free HIV-RNA, while HIVgag or pol-DNA was detectable in 13 of 18 (72%, 95% confidence interval: 47–90). Detectable HIV-DNA in CSF was associated with male sex-at-birth (P = 0.051), lower CD4+ cell count at enrollment (P = 0.016), and higher PBMC HIVpol-DNA copies (P = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. Conclusion: We found that a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.