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Low-Level HIV in CSF When HIV-RNA is < 50 Tied to Type of ART and Worse Cognitive Function
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16th Conference on Retroviruses and Opportunistic Infections,
February 8-11, 2009, Montreal
Mark Mascolini
More than a quarter of HIV-infected people in a US cohort with 2 to 50 copies of HIV RNA in cerebrospinal fluid (CSF) did not have detectable virus in blood, but they had worse neurocognitive function than people with detectable HIV RNA in blood and CSF [1]. Scott Letendre and CHARTER cohort colleagues found evidence implicating antiretrovirals that penetrate CSF poorly in cognitive impairment due to low-level CSF virus.
CHARTER cohort members live in Baltimore, Galveston, New York, St. Louis, San Diego, and Seattle. This study involved 300 people who had lumbar punctures while taking antiretrovirals, had an HIV RNA load below 50 copies in CSF and blood by standard assays, and had at least a 2-mL, properly stored CSF specimen. Everyone completed an array of neuropsychological tests known to be reliable in people with HIV.
The investigators measured HIV RNA in CSF with an ultrasensitive assay that detects levels below 50 copies. For everyone in whom this test spotted low-level virus in CSF, Letendre and coworkers remeasured HIV RNA in blood samples collected within an hour of the CSF sample. Finally, they figured how well each person's antiretroviral regimen penetrated CSF by using the CNS Penetration-Effectiveness (CPE) score [2].
Study participants had a median age of 45 years, 76% were men, 46% were white, and 48% had global cognitive impairment. Current median CD4 count stood at 482 and lowest-ever CD4 count a 115. These people had taken their current antiretroviral regimen for a median of 18 months.
Of the 300 study participants, 122 (41%) had low-level HIV RNA in CSF that standard assays missed. Only 26% of matched blood samples had detectable HIV RNA. People with detectable virus in CSF had an average CPE score of 50.8%, compared with 63.5% in those without HIV in CSF (P = 0.03). Use of tenofovir (versus abacavir), emtricitabine (versus lamivudine), or efavirenz (versus nevirapine) raised the risk of having HIV in CSF.
People with HIV detectable in CSF but not in plasma had significantly worse neurocognitive impairment than those with detectable HIV in both CSF and plasma (P = 0.006). And neurocognitive performance worsened in a higher proportion of people with HIV detectable in CSF but not plasma than in people with detectable HIV in both fluids (21% vs 14%), but this difference was not statistically significant.
Letendre and colleagues concluded that antiretroviral-treated people "may be cognitively impaired because of incomplete suppression of HIV in the central nervous system by therapy that does not sufficiently penetrate the blood-brain barrier." They proposed that more sensitive CSF assays could improve management of people with HIV.
References
1. Letendre S, McClernon D Ellis R, et al. Persistent HIV in the central nervous system during treatment is associated with worse ART penetration and cognitive impairment. 16th Conference on Retroviruses and Opportunistic Infections, February 8-11, 2009, Montreal. Abstract 484b.
2. Letendre S, Marquie-Beck J, Capparelli E, et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008;65:65-70.
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