SSRIs and reduction of viral load

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The Role of Cohort Studies in Drug Development: Clinical Evidence of

Antiviral Activity of Serotonin Reuptake Inhibitors and HMG-CoA

Reductase Inhibitors in the Central Nervous System

Journal Journal of Neuroimmune Pharmacology

<http://www.springerlink.com/content/119975/?p=61a3757eb7034f3f82da3ea52a1b68fe & \

pi=0>

Publisher Springer New York

ISSN 1557-1890 (Print) 1557-1904 (Online)

Issue Volume 2, Number 1 / March, 2007

<http://www.springerlink.com/content/m49h28w358qp/?p=61a3757eb7034f3f82da3ea52a1\

b68fe & pi=0>

Category Original Article

DOI 10.1007/s11481-006-9054-y

Pages 120-127

Subject Collection Biomedical and Life Sciences

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SpringerLink Date Wednesday, January 03, 2007

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Original Article

The Role of Cohort Studies in Drug Development: Clinical Evidence of

Antiviral Activity of Serotonin Reuptake Inhibitors and HMG-CoA

Reductase Inhibitors in the Central Nervous System

L. Letendre1 Contact Information

<http://www.springerlink.com/content/64673j165353u750/#ContactOfAuthor1>,

Marquie-Beck1, J. Ellis1, Woods1,

Brookie Best1, B. Clifford2, Ann C. Collier3, B. Gelman4,

Marra3, C. McArthur5, J. McCutchan1,

Morgello6, Simpson6, Terry J. 1, Janis Durelle1,

Heaton1, Igor Grant1 and The CHARTER Group

(1) University of California, 150 W. Washington St., San Diego,

CA 92103, USA

(2) Washington University, St. Louis, MO, USA

(3) University of Washington, Seattle, WA, USA

(4) University of Texas Medical Branch, Galveston, TX, USA

(5) s Hopkins University, Baltimore, MD, USA

(6) Mt. Sinai School of Medicine, New York, NY, USA

Received: 18 September 2006 Accepted: 5 December 2006 Published

online: 3 January 2007

Abstract

Background Effective 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 Food and Drug

Administration (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 and are already widely used by HIV-infected

individuals.

Methods Six-hundred fifty-eight HIV-infected participants of the

CHARTER cohort had a baseline assessment, which included comprehensive

neuropsychological (NP) testing and HIV RNA measurements in plasma and

cerebrospinal fluid (CSF). Four-hundred sixty-seven (71%) subjects used

ART, 195 (30%) used SRIs, and 63 (10%) used statins.

Results SRI users were less likely to have HIV RNA levels in CSF above

50 copies ©/mL (29 vs. 37% in non-SRI users, OR 0.69, p=0.05). This

association was most evident for three of the seven SRIs (citalopram,

sertraline, and trazodone, or " antiviral " SRIs, combined 25 vs. 38% in

non-SRI users, OR 0.56, p=0.01) and was strongest in those not taking

concomitant ART (61 vs. 83%, OR 0.31, p=0.01). " Antiviral " SRI users

also performed better on NP 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 above 50 c/mL (16 vs. 37%, p<0.001) but, in contrast to SRIs, the

association was strongest in those taking ART (2 vs. 18%, p<0.001).

Statin use was not associated with better NP performance. Multivariate

analyses indicated that the use of " antiviral " SRIs--but not

statins--was associated with undetectable HIV RNA levels in CSF and

better NP performance.

Conclusions SRIs may reduce HIV replication in CSF and improve NP

performance. This was particularly true for three SRIs--supporting

differences in antiviral efficacy between drugs--in individuals who were

not taking ART. In contrast, statins were not associated with lower HIV

replication in CSF in multivariate analyses and were not associated with

better NP performance. These analyses support the value of large

observational cohort studies in identifying FDA-approved drugs that may

be worth further investigation.

http://www.springerlink.com/content/64673j165353u750/

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[Guest guest]

>

>

> excellent, thanks for posting. The link did not work for me, here is the

> abstract from another site:

>

> Abstract

Background Effective 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 Food and Drug Administration (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 and are already

widely used by HIV-infected individuals.

Methods Six-hundred fifty-eight HIV-infected participants of the CHARTER

cohort had a baseline assessment, which included comprehensive

neuropsychological (NP) testing and HIV RNA measurements in plasma and

cerebrospinal fluid (CSF). Four-hundred sixty-seven (71%) subjects used ART,

195 (30%) used SRIs, and 63 (10%) used statins.

Results SRI users were less likely to have HIV RNA levels in CSF above 50

copies ©/mL (29 vs. 37% in non-SRI users, OR 0.69, p = 0.05). This

association was most evident for three of the seven SRIs (citalopram,

sertraline, and trazodone, or “antiviral†SRIs, combined 25 vs. 38% in

non-SRI users, OR 0.56, p = 0.01) and was strongest in those not taking

concomitant ART (61 vs. 83%, OR 0.31, p = 0.01). “Antiviral†SRI users

also

performed better on NP 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

above 50 c/mL (16 vs. 37%, p < 0.001) but, in contrast to SRIs, the

association was strongest in those taking ART (2 vs. 18%, p < 0.001). Statin

use was not associated with better NP performance. Multivariate analyses

indicated that the use of “antiviral†SRIs—but not statins—was

associated

with undetectable HIV RNA levels in CSF and better NP performance.

Conclusions SRIs may reduce HIV replication in CSF and improve NP

performance. This was particularly true for three SRIs—supporting

differences in antiviral efficacy between drugs—in individuals who were not

taking ART. In contrast, statins were not associated with lower HIV

replication in CSF in multivariate analyses and were not associated with

better NP performance. These analyses support the value of large

observational cohort studies in identifying FDA-approved drugs that may be

worth further investigation.

>

>

>

>

>

>

>

> The Role of Cohort Studies in Drug Development: Clinical Evidence of

> Antiviral Activity of Serotonin Reuptake Inhibitors and HMG-CoA

> Reductase Inhibitors in the Central Nervous System

>

> Journal Journal of Neuroimmune Pharmacology

> <http://www.springerlink.com/content/119975/?p=61a3757eb7034f3f82da3ea52a1b68f

> e & pi=0

> <http://www.springerlink.com/content/119975/?p=61a3757eb7034f3f82da3ea52a1b68f

> e & amp;pi=0>

> <http://www.springerlink.com/content/119975/?p=61a3757eb7034f3f82da3ea52a1b68f

> e & pi=0 > >

>

> Publisher Springer New York

> ISSN 1557-1890 (Print) 1557-1904 (Online)

> Issue Volume 2, Number 1 / March, 2007

> <http://www.springerlink.com/content/m49h28w358qp/?p=61a3757eb7034f3f82da3ea52

> a1b68fe & pi=0

> <http://www.springerlink.com/content/m49h28w358qp/?p=61a3757eb7034f3f82da3ea52

> a1b68fe & amp;pi=0>

> <http://www.springerlink.com/content/m49h28w358qp/?p=61a3757eb7034f3f82da3ea52

> a1b68fe & pi=0 > >

>

> Category Original Article

> DOI 10.1007/s11481-006-9054-y

> Pages 120-127

> Subject Collection Biomedical and Life Sciences

> <http://www.springerlink.com/biomedical-and-life-sciences/>

> SpringerLink Date Wednesday, January 03, 2007

>

>

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> ity+of+Serotonin+Reuptake+Inhibitors+and+HMG-CoA+Reductase+Inhibitors+in+the+C

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> Original Article

>

> The Role of Cohort Studies in Drug Development: Clinical Evidence of

> Antiviral Activity of Serotonin Reuptake Inhibitors and HMG-CoA

> Reductase Inhibitors in the Central Nervous System

>

> L. Letendre1 Contact Information

> <http://www.springerlink.com/content/64673j165353u750/#ContactOfAuthor1>,

> Marquie-Beck1, J. Ellis1, Woods1,

> Brookie Best1, B. Clifford2, Ann C. Collier3, B. Gelman4,

> Marra3, C. McArthur5, J. McCutchan1,

> Morgello6, Simpson6, Terry J. 1, Janis Durelle1,

> Heaton1, Igor Grant1 and The CHARTER Group

>

> (1) University of California, 150 W. Washington St., San Diego,

> CA 92103, USA

>

> (2) Washington University, St. Louis, MO, USA

>

> (3) University of Washington, Seattle, WA, USA

>

> (4) University of Texas Medical Branch, Galveston, TX, USA

>

> (5) s Hopkins University, Baltimore, MD, USA

>

> (6) Mt. Sinai School of Medicine, New York, NY, USA

>

> Received: 18 September 2006 Accepted: 5 December 2006 Published

> online: 3 January 2007

>

> Abstract

> Background Effective 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 Food and Drug

> Administration (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 and are already widely used by HIV-infected

> individuals.

> Methods Six-hundred fifty-eight HIV-infected participants of the

> CHARTER cohort had a baseline assessment, which included comprehensive

> neuropsychological (NP) testing and HIV RNA measurements in plasma and

> cerebrospinal fluid (CSF). Four-hundred sixty-seven (71%) subjects used

> ART, 195 (30%) used SRIs, and 63 (10%) used statins.

> Results SRI users were less likely to have HIV RNA levels in CSF above

> 50 copies ©/mL (29 vs. 37% in non-SRI users, OR 0.69, p=0.05). This

> association was most evident for three of the seven SRIs (citalopram,

> sertraline, and trazodone, or " antiviral " SRIs, combined 25 vs. 38% in

> non-SRI users, OR 0.56, p=0.01) and was strongest in those not taking

> concomitant ART (61 vs. 83%, OR 0.31, p=0.01). " Antiviral " SRI users

> also performed better on NP 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 above 50 c/mL (16 vs. 37%, p<0.001) but, in contrast to SRIs, the

> association was strongest in those taking ART (2 vs. 18%, p<0.001).

> Statin use was not associated with better NP performance. Multivariate

> analyses indicated that the use of " antiviral " SRIs--but not

> statins--was associated with undetectable HIV RNA levels in CSF and

> better NP performance.

> Conclusions SRIs may reduce HIV replication in CSF and improve NP

> performance. This was particularly true for three SRIs--supporting

> differences in antiviral efficacy between drugs--in individuals who were

> not taking ART. In contrast, statins were not associated with lower HIV

> replication in CSF in multivariate analyses and were not associated with

> better NP performance. These analyses support the value of large

> observational cohort studies in identifying FDA-approved drugs that may

> be worth further investigation.

>

> http://www.springerlink.com/content/64673j165353u750/

> <http://www.springerlink.com/content/64673j165353u750/>

>

>