Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients

Research output: Contribution to journalArticle

Abstract

Objective: To determine the effectiveness of antiretroviral therapy in controlling cerebrospinal fluid (CSF) HIV-1 replication and to assess factors related to virological response in advanced patients. Design: A cross-sectional and longitudinal study. Methods: Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART). Results: In the cross-sectional analysis 75 patients were included, 55 (73%) with neurological disease, 28 (37%) naive for antiretroviral agents. A significant correlation between plasma and CSF levels at baseline was observed only in antiretroviral-experienced patients. The absence of neurological disease, lower plasma HIV-1 load and a previous exposure to indinavir were all associated with a baseline CSF HIV-1-RNA level less than 80 copies/ml at multivariate analysis. In 29 patients included in the longitudinal study a significant reduction in CSF HIV-1 RNA was observed. Plasma HIV-1-RNA change, CSF HIV-1-RNA level at baseline, overall months of antiretroviral treatment and the magnitude of difference between plasma and CSF HIV-1-RNA levels were all correlated to CSF HIV-1-RNA change during treatment. A significant difference in the magnitude of CSF HIV-1-RNA reduction was observed according to naive status and to the use of three or more drugs penetrating the blood-brain barrier. Conclusion: HAART effectively reduces HIV-1 replication in CSF. A variable response to antiretroviral therapy was observed in CSF, reflecting a different compartmentalization of infection during treatment. Naive status and the use of CNS-penetrating drugs substantially enhance antiviral response. A negative interaction between virological response and the duration of antiretroviral treatment suggests long-term selection of drug-resistant CSF HIV-1 strains.

Original languageEnglish
Pages (from-to)1867-1876
Number of pages10
JournalAIDS (London, England)
Volume16
Issue number14
DOIs
Publication statusPublished - Sep 27 2002

Fingerprint

Cerebrospinal Fluid
HIV-1
Pharmaceutical Preparations
RNA
Highly Active Antiretroviral Therapy
Longitudinal Studies
Therapeutics
Cross-Sectional Studies
Anti-Retroviral Agents
Indinavir
Blood-Brain Barrier
Antiviral Agents
Multivariate Analysis

Keywords

  • AIDS
  • Cerebrospinal fluid
  • Highly active antiretroviral therapy
  • HIV
  • HIV-1 RNA

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

@article{ed35441f95314858b27477094af39440,
title = "Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients",
abstract = "Objective: To determine the effectiveness of antiretroviral therapy in controlling cerebrospinal fluid (CSF) HIV-1 replication and to assess factors related to virological response in advanced patients. Design: A cross-sectional and longitudinal study. Methods: Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART). Results: In the cross-sectional analysis 75 patients were included, 55 (73{\%}) with neurological disease, 28 (37{\%}) naive for antiretroviral agents. A significant correlation between plasma and CSF levels at baseline was observed only in antiretroviral-experienced patients. The absence of neurological disease, lower plasma HIV-1 load and a previous exposure to indinavir were all associated with a baseline CSF HIV-1-RNA level less than 80 copies/ml at multivariate analysis. In 29 patients included in the longitudinal study a significant reduction in CSF HIV-1 RNA was observed. Plasma HIV-1-RNA change, CSF HIV-1-RNA level at baseline, overall months of antiretroviral treatment and the magnitude of difference between plasma and CSF HIV-1-RNA levels were all correlated to CSF HIV-1-RNA change during treatment. A significant difference in the magnitude of CSF HIV-1-RNA reduction was observed according to naive status and to the use of three or more drugs penetrating the blood-brain barrier. Conclusion: HAART effectively reduces HIV-1 replication in CSF. A variable response to antiretroviral therapy was observed in CSF, reflecting a different compartmentalization of infection during treatment. Naive status and the use of CNS-penetrating drugs substantially enhance antiviral response. A negative interaction between virological response and the duration of antiretroviral treatment suggests long-term selection of drug-resistant CSF HIV-1 strains.",
keywords = "AIDS, Cerebrospinal fluid, Highly active antiretroviral therapy, HIV, HIV-1 RNA",
author = "Andrea Antinori and Giancola, {Maria Letizia} and Susanna Grisetti and Fabio Soldani and Lucia Alba and Giuseppina Liuzzi and Alessandra Amendola and Maria Capobianchi and Valerio Tozzi and Perno, {Carlo Federico}",
year = "2002",
month = "9",
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doi = "10.1097/00002030-200209270-00003",
language = "English",
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pages = "1867--1876",
journal = "AIDS",
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TY - JOUR

T1 - Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients

AU - Antinori, Andrea

AU - Giancola, Maria Letizia

AU - Grisetti, Susanna

AU - Soldani, Fabio

AU - Alba, Lucia

AU - Liuzzi, Giuseppina

AU - Amendola, Alessandra

AU - Capobianchi, Maria

AU - Tozzi, Valerio

AU - Perno, Carlo Federico

PY - 2002/9/27

Y1 - 2002/9/27

N2 - Objective: To determine the effectiveness of antiretroviral therapy in controlling cerebrospinal fluid (CSF) HIV-1 replication and to assess factors related to virological response in advanced patients. Design: A cross-sectional and longitudinal study. Methods: Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART). Results: In the cross-sectional analysis 75 patients were included, 55 (73%) with neurological disease, 28 (37%) naive for antiretroviral agents. A significant correlation between plasma and CSF levels at baseline was observed only in antiretroviral-experienced patients. The absence of neurological disease, lower plasma HIV-1 load and a previous exposure to indinavir were all associated with a baseline CSF HIV-1-RNA level less than 80 copies/ml at multivariate analysis. In 29 patients included in the longitudinal study a significant reduction in CSF HIV-1 RNA was observed. Plasma HIV-1-RNA change, CSF HIV-1-RNA level at baseline, overall months of antiretroviral treatment and the magnitude of difference between plasma and CSF HIV-1-RNA levels were all correlated to CSF HIV-1-RNA change during treatment. A significant difference in the magnitude of CSF HIV-1-RNA reduction was observed according to naive status and to the use of three or more drugs penetrating the blood-brain barrier. Conclusion: HAART effectively reduces HIV-1 replication in CSF. A variable response to antiretroviral therapy was observed in CSF, reflecting a different compartmentalization of infection during treatment. Naive status and the use of CNS-penetrating drugs substantially enhance antiviral response. A negative interaction between virological response and the duration of antiretroviral treatment suggests long-term selection of drug-resistant CSF HIV-1 strains.

AB - Objective: To determine the effectiveness of antiretroviral therapy in controlling cerebrospinal fluid (CSF) HIV-1 replication and to assess factors related to virological response in advanced patients. Design: A cross-sectional and longitudinal study. Methods: Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART). Results: In the cross-sectional analysis 75 patients were included, 55 (73%) with neurological disease, 28 (37%) naive for antiretroviral agents. A significant correlation between plasma and CSF levels at baseline was observed only in antiretroviral-experienced patients. The absence of neurological disease, lower plasma HIV-1 load and a previous exposure to indinavir were all associated with a baseline CSF HIV-1-RNA level less than 80 copies/ml at multivariate analysis. In 29 patients included in the longitudinal study a significant reduction in CSF HIV-1 RNA was observed. Plasma HIV-1-RNA change, CSF HIV-1-RNA level at baseline, overall months of antiretroviral treatment and the magnitude of difference between plasma and CSF HIV-1-RNA levels were all correlated to CSF HIV-1-RNA change during treatment. A significant difference in the magnitude of CSF HIV-1-RNA reduction was observed according to naive status and to the use of three or more drugs penetrating the blood-brain barrier. Conclusion: HAART effectively reduces HIV-1 replication in CSF. A variable response to antiretroviral therapy was observed in CSF, reflecting a different compartmentalization of infection during treatment. Naive status and the use of CNS-penetrating drugs substantially enhance antiviral response. A negative interaction between virological response and the duration of antiretroviral treatment suggests long-term selection of drug-resistant CSF HIV-1 strains.

KW - AIDS

KW - Cerebrospinal fluid

KW - Highly active antiretroviral therapy

KW - HIV

KW - HIV-1 RNA

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