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Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders
Author(s) -
Letendre Scott L.,
McCutchan J. Allen,
Childers Meredith E.,
Woods Steven P.,
Lazzaretto Deborah,
Heaton Robert K.,
Grant Igor,
Ellis Ronald J.
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20198
Subject(s) - viral load , medicine , regimen , cerebrospinal fluid , neuropsychology , antiretroviral therapy , human immunodeficiency virus (hiv) , cognitive decline , multivariate analysis , immunology , oncology , cognition , dementia , psychiatry , disease
The benefits of combination antiretroviral therapy (ART) for HIV cognitive disorders vary substantially between individuals. This study evaluated whether cerebrospinal fluid (CSF) drug penetration and CSF virological suppression influence the extent of neuropsychological (NP) improvement during ART. Overall performance on a battery of NP tests administered at baseline and follow‐up (median 15 weeks) was computed by using the global deficit score (GDS) methods in 31 cognitively impaired, HIV‐infected individuals who began new ART regimens. Virological suppression (attaining undetectable viral load by RT‐PCR at follow‐up) was assessed separately for plasma and CSF. Subjects on regimens containing greater numbers of CSF‐penetrating drugs showed significantly greater reduction in CSF viral load. Subjects attaining CSF virological suppression demonstrated greater GDS improvement than those who did not (median GDS change, 0.62 vs 0.23; p = 0.01). A similar trend for plasma did not reach statistical significance ( p = 0.053). NP improvement was greater in ART‐naive versus treatment‐experienced subjects. In a multivariate model (overall p = 0.0008), significant, independent predictors of GDS reduction were CSF HIV RNA suppression, baseline antiretroviral history, and their interaction. Including CSF‐penetrating drugs in the ART regimen and monitoring CSF viral load may be indicated for individuals with HIV‐associated cognitive impairment Ann Neurol 2004.