Prevalence and Correlates of Persistent HIV-1 RNA in Cerebrospinal Fluid During Antiretroviral Therapy

Abstract

Background: Neurocognitive disorders remain common among human immunodeficiency virus (HIV)-positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART).

Methods: Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice.

Results: HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4⁺ T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months.

Conclusions: Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4⁺ T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.

Keywords: HIV; antiretroviral therapy; cerebrospinal fluid; cognitive disorders.

Figure 1.

A, Distribution of human immunodeficiency virus type 1 (HIV-1) RNA levels among the 93 participants with values of ≥1 copy/mL. B, Although HIV-1 RNA levels in cerebrospinal fluid (CSF) did not correlate with those in plasma (not shown), participants who had HIV-1 RNA levels of ≥1 copy/mL in plasma had higher HIV-1 RNA levels in CSF. For clarity, the bars indicating mean values and 95% confidence intervals are shown next to the data points, rather than superimposed over them.

Figure 2.

A, Lower human immunodeficiency virus type 1 (HIV-1) RNA levels in cerebrospinal fluid (CSF) correlated with worse global neurocognitive performance. B, The discordant group with an HIV-1 RNA of ≥1 copy/mL in CSF but a level of <1 copy in plasma (the CSF+Plasma− group) had worse neurocognitive performance than the group with an HIV-1 RNA level of ≥ 1 copy/mL in both fluids (the CSF+Plasma+ group). The dashed line indicates the threshold value for impairment (5). Global impairment was present in 60.7% of the CSF+Plasma− group, compared with 41.5% of the CSF+Plasma+ group (P = .09).

Figure 3.

Having a human immunodeficiency virus type 1 (HIV-1) RNA level of < 1 copy/mL in cerebrospinal fluid (CSF) at the first and second visits was associated with improved neurocognitive performance over time.