Background
The central nervous system (CNS) reservoir for HIV during ART has implications for both HIV cure and clinical outcomes. HIV DNA has been cross-sectionally detected in cerebrospinal fluid (CSF) cells but the longitudinal dynamics of HIV DNA in CSF during long-term suppressive ART are unknown.
Methods
16 participants in ACTG A5321/A5341s who started ART during chronic infection and had documented long-term suppression of plasma HIV RNA underwent 4-5 serial lumbar punctures (LP) over a span of 2.4-4.4 years. Cell pellets from ~13mL of CSF were assayed for total HIV DNA and cell-associated HIV RNA; cell-free HIV RNA by single copy assay was measured from CSF supernatant. Geometric means of longitudinal measurements were calculated using censored-data methods, analyzing both quantifiable and below assay limit values, and used for Spearman correlation analyses.
Results
The participants (100% male) had a median (IQR) age of 56 (50, 59) years, and were on ART for median 9 (range 6-16) years at their first LP. All participants had HIV DNA detected in CSF at one or more time points, and in total, 48/79 samples assayed had detectable HIV DNA. 11/16 participants (69%) had detectable HIV DNA in CSF at ≥ 3 timepoints, based on a median of 4,400 cells assayed. There was no evidence for a decay in CSF HIV DNA over time (Figure 1; p=0.8 from a censored-data model). The geometric mean of each participant’s CSF HIV DNA across time points correlated with the amount of HIV DNA in blood measured near the time of the first LP (r=0.45, p=0.09) but no correlations were evident with pre-ART plasma HIV RNA, pre-ART CD4 cell count, or duration of ART. Cell-free HIV RNA in CSF was only detectable in 2 participants, at 1 or 2 time points (3 of 77 assays performed, with levels 1-4 copies/mL). Cell-associated HIV RNA in CSF was detectable in 3 participants, each at a single time point.
Conclusions
In a longitudinal study in which 4-5 serial LP were obtained over 2-4 years in people on ART for 6-19 years, HIV DNA was found to persist in CSF in most participants with no evidence of decay. These findings highlight the ongoing exposure of the CNS to infected cells during long-term ART, and the need to further understand the characteristics and pathobiological relevance of cells harboring HIV DNA in the CSF compartment.
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