Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment

Theresa K. Smit, Bruce J. Brew, Wallace Tourtellotte, Susan Morgello, Benjamin Gelman, Nitin K. Saksena

Research output: Contribution to journalArticle

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Abstract

AIDS dementia complex (ADC) in human immunodeficiency virus (HIV)-infected patients continues to be a problem in the era of highly active antiretroviral therapy (HAART). A better understanding of the drug resistance mutation patterns that emerge in the central nervous system (CNS) during HAART is of paramount importance as these differences in drug resistance mutations may explain underlying reasons for poor penetration of antiretroviral drugs into the CNS and suboptimal concentrations of the drugs that may reside in the brains of HIV-infected individuals during therapy. Thus, we provide a detailed analysis of HIV type 1 (HIV-1) protease and reverse transcriptase (RT) genes derived from different regions of the brains of 20 HIV-1-infected patients (5 without ADC, 2 with probable ADC, and 13 with various stages of ADC) on antiretroviral therapy. We show the compartmentalization and independent evolution of both primary and secondary drug resistance mutations to both RT and protease inhibitors in diverse regions of the CNS of HIV-infected patients, with and without dementia, on antiretroviral therapy. Our results suggest that the independent evolution of drug resistance mutations in diverse areas of the CNS may emerge as a consequence of incomplete suppression of HIV, probably related to suboptimal drug levels in the CNS and drug selection pressure. The emergence of resistant virus in the CNS may have considerable influence on the outcome of neurologic disease and also the reseeding of HIV in the systemic circulation upon failure of therapy.

Original languageEnglish (US)
Pages (from-to)10133-10148
Number of pages16
JournalJournal of Virology
Volume78
Issue number18
DOIs
StatePublished - Sep 2004

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dementia
AIDS Dementia Complex
Human immunodeficiency virus
drug resistance
Drug Resistance
central nervous system
Dementia
HIV
mutation
brain
Central Nervous System
therapeutics
Mutation
Central Nervous System Agents
Brain
Highly Active Antiretroviral Therapy
RNA-directed DNA polymerase
HIV-1
Human immunodeficiency virus 1
drugs

ASJC Scopus subject areas

  • Immunology

Cite this

Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment. / Smit, Theresa K.; Brew, Bruce J.; Tourtellotte, Wallace; Morgello, Susan; Gelman, Benjamin; Saksena, Nitin K.

In: Journal of Virology, Vol. 78, No. 18, 09.2004, p. 10133-10148.

Research output: Contribution to journalArticle

Smit, Theresa K. ; Brew, Bruce J. ; Tourtellotte, Wallace ; Morgello, Susan ; Gelman, Benjamin ; Saksena, Nitin K. / Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment. In: Journal of Virology. 2004 ; Vol. 78, No. 18. pp. 10133-10148.
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