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Select resistance-associated mutations in blood are associated with lower CSF viral loads and better neuropsychological performance.

Abstract：

BACKGROUND:When antiretroviral therapy does not fully suppress HIV replication, suboptimal levels of antiretrovirals can select for antiretroviral resistant variants of HIV. These variants may exhibit reduced replication capacity and result in lower viral loads in blood. Our study evaluated whether antiretroviral resistance was associated with viral loads in the cerebrospinal fluid (CSF) and better neuropsychological (NP) performance. METHODS:We enrolled 94 participants and each participant underwent a comprehensive neuromedical evaluation that used structured clinical assessments of medical history, ART and other medication use, comprehensive NP testing, and neurological and general physical signs of disease. Blood was collected by venipuncture, and all participants were offered lumbar puncture. Univariate and multivariate statistical methods were used to analyze the relationship between antiretroviral resistance, blood and CSF HIV RNA levels, substance use, and NP performance. RESULTS:Antiretroviral resistance, detected in blood, was associated with lower CSF viral loads (p<0.01) and better NP performance (p=0.04) in multivariate analyses, independent of past and current ARV use and blood viral loads (model: p<0.01). However, HIV RNA levels in CSF did not independently correlate with NP performance. Low viral loads in the CSF limited our ability to investigate the relationship between antiretroviral resistance detected in CSF and NP performance. CONCLUSIONS:Even in the absence of ART, antiretroviral resistance-associated mutations correlate with better NP performance possibly because these mutations reflect reduced neurovirulence compared with wild-type HIV.

journal_name

Virology

journal_title

Virology

authors

Hightower GK,Letendre SL,Cherner M,Gibson SA,Ellis RJ,Wolfson TJ,Gamst AC,Ignacio CC,Heaton RK,Grant I,Richman DD,Smith DM,HNRC Group.

doi

10.1016/j.virol.2009.08.007

subject

Has Abstract

pub_date

2009-11-25 00:00:00

pages

243-8

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(09)00487-5

journal_volume

394

pub_type

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