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Clinical Evidence of Antiviral Activity of Serotonin Reuptake Inhibitors and HMG-CoA Reductase Inhibitors in the Central Nervous System
Scott Letendre*1, J Marquie-Beck1, D Clifford2, A Collier3, B Gelman4, J McArthur5, J McCutchan1, D Simpson6, I Grant1, R Ellis1, and CHARTER Group
1Univ of California, San Diego, US; 2Washington Univ, St Louis, MO, US; 3Univ of Washington, Seattle, US; 4Univ of Texas Med Branch, Galveston, US; 5Johns Hopkins Univ, Baltimore, MD, US; and 6Mt Sinai Sch of Med, New York, NY, US
Background: ART has reduced the incidence of HIV-associated neurocognitive impairment, but its prevalence remains high.
Clinical trials have yet to identify a consistently effective treatment for
HIV-associated neurocognitive impairment, other than
ART, but in vitro data support that
some drugs approved by the FDA for other indications might benefit individuals
with HIV-associated neurocognitive impairment. Some
of these drugs, such as serotonin reuptake inhibitors (SRI) and HMG-CoA reductase inhibitors (statins), may do so by reducing HIV replication in the central
nervous system.
Methods: A baseline assessment for 658 HIV-infected
participants of the CHARTER study, a North American observational cohort,
included comprehensive neuropsychological testing and HIV RNA measurements in
plasma and cerebrospinal fluid (CSF): 467
(71%) used ART, 195 (30%) used SRI, and 63 (10%) used statins.
Results: SRI users were less likely to have HIV RNA
levels >50 copies/mL in CSF (29% vs 37% in non-SRI users, OR 0.69, p = 0.05). This association was most evident for 3 of the 7 SRI (citalopram, sertraline, and trazodone, or “antiviral” SRI, combined 25% vs 38% in non-SRI users, OR 0.56, p = 0.01) and was limited to those not taking concomitant ART (61% vs 83%, OR 0.31, p
= 0.01). “Antiviral” SRI users also performed better on neuropsychological
tests (median global deficit score 0.37 vs 0.47, p = 0.04). Statin
users were also less likely to have HIV RNA levels in CSF >50 copies/mL (16% vs 37%, p <0.001). In contrast to SRI, statins showed the strongest association in those using ART
(2% vs 18%, p
<0.001). Statin use was not associated with better
neuropsychological performance. Multivariate analyses indicated that use of
“antiviral” SRI—but not statins—was associated with undetectable
HIV RNA levels in CSF and better neuropsychological performance after adjusting
for HIV RNA levels in plasma, ART use, AIDS diagnosis, and current CD4 count.
Conclusions: SRI may both reduce HIV replication in CSF and
improve neuropsychological performance. This was particularly true for 3 SRI in
this analysis—supporting differences in antiviral efficacy between drugs—and in
those not taking ART. In contrast, statins were not
associated with lower HIV replication in CSF in multivariate analyses and were
not associated with better neuropsychological performance. These analyses support
further investigation of SRI as adjunctive treatment for the neurologic complications of HIV.
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