| Publication Abstract Display | | Type: Poster | | Title: Clinical evidence of antiviral activity of serotonin reuptake inhibitors and HMG-CoA reductase inhibitors in the central nervous system. | | Authors: Letendre S, Marquie-Beck J, Clifford D, Collier A, Gelman B,McArthur J, McCutchan J, Simpson D, Grant I, Ellis R, and the CHARTER Group | | Date: 02-25-2007 | | Abstract:Background: Antiretroviral therapy (ART) has reduced the incidence of HIV-associated
neurocognitive impairment (HNCI), but its prevalence remains high. Clinical trials have yet to
identify a consistently effective treatment for HNCI, other than ART, but in vitro data support
that some drugs approved by the FDA for other indications might benefit individuals with
HNCI. Some of these drugs, such as serotonin reuptake inhibitors (SRIs) and HMG-CoA
reductase inhibitors (statins), may do so by reducing HIV replication in the CNS.
Methods: 658 HIV-infected participants of the CHARTER study, a North American
observational cohort, had a baseline assessment, which included comprehensive
neuropsychological (NP) testing and HIV RNA measurements in plasma and cerebrospinal
fluid. 467 (71%) used ART, 195 (30%) used SRIs, and 63 (10%) used statins.
Results: SRI users were less likely to have HIV RNA levels above 50 c/mL in CSF (29% vs.
37% in non-SRI users, OR=.69, p=.05). This association was most evident for 3 of the 7
SRIs (citalopram, sertraline, and trazodone, or “antiviral” SRIs, combined 25% vs. 38% in
non-SRI users, OR=.56, p=.01) and was limited to those not taking concomitant ART (61%
vs. 83%, OR=.31, p = .01). “Antiviral” SRI users also performed better on NP tests (median
global deficit score .37 vs. .47, p=.04). Statin users were also less likely to have HIV RNA
levels in CSF above 50 c/mL (16% vs. 37%, p<.001). In contrast to SRIs, statins showed the
strongest association in those using ART (2% vs. 18%, p<.001). Statin use was not
associated with better NP performance. Multivariate analyses indicated that use of “antiviral”
SRIs – 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: SRIs may both reduce HIV replication in CSF and improve neuropsychological
performance. This was particularly true for 3 SRIs 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 SRIs as adjunctive treatment for the neurologic complications of HIV |
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