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HIV-RNA common in spinal fluid of patients receiving ART
The presence of small amounts of HIV-1 RNA in cerebrospinal fluid is common among patients receiving suppressive ART, study data show. According to researchers, the association between HIV-1 RNA discordance and HIV–associated neurocognitive disorder, or HAND, may be the result of compartmentalization.
“Potent ART can reduce HIV-1 in blood and cerebrospinal fluid (CSF) below the quantification limit of commercially available assays, but HIV-1 might continue to replicate at low levels, increasing the risk for viral compartmentalization in the central nervous system (CNS),” Albert M. Anderson, MD, of Emory University School of Medicine, and colleagues wrote. “Persistent low-level HIV-1 replication could also lead to glial activation and neuronal injury. Published reports have identified that low-level HIV-1 is present in CSF in up to 28% of adults taking ART, but have not found associations with estimated ART drug distribution into the CNS or neurocognitive outcomes.”
Anderson and colleagues used a single-copy assay to measure HIV-1 RNA in the plasma and CSF of adults with HIV who were receiving ART (n = 220). Fifty-five patients underwent a second test. The median patient age was 44 years, and 22.6% were women.
The researchers detected HIV-1 RNA in 65.2% of plasma samples and 42.3% of CSF samples. Twenty-eight (12.7%) participants had discordant HIV-1 RNA, with less than 1 c/mL in blood samples and 1 c/mL or more in CSF. Poor cognitive performance was associated with lower HIV-1 RNA in CSF, HIV-1 RNA discordance and longer duration of ART (model P < .001 for all), Anderson and colleagues reported. Higher levels of HIV-1 RNA in CSF were correlated with higher nadir and current CD4 counts, lower CNS penetration-effectiveness values and plasma HIV-1 RNA (model P < .001 for all).
Anderson and colleagues wrote that the relationship between lower CD4 counts, low HIV-1 RNA in CSF and HAND “may reflect disturbances in the immune response to HIV-1 in the CNS.”
These findings may “support a complex approach for HAND management in which clinicians should consider ART drug characteristics, CD4 counts, neuropsychiatric conditions and coinfections, among others,” they wrote. “The best approach may be the use of ART regimens that balance sufficient potency in the central nervous system with the absence of neurotoxicity, similar to those currently recommended by the US Department of Health and Human Services. Ultimately, randomized controlled trials of ART regimens will be needed to inform the clinical management of HAND.” – by Andy Polhamus
Disclosure: Anderson reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.