Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients
作者:
Andrea Antinori,
Maria Giancola,
Susanna Grisetti,
Fabio Soldani,
Lucia Alba,
Giuseppina Liuzzi,
Alessandra Amendola,
Maria Capobianchi,
Valerio Tozzi,
Carlo Perno,
期刊:
AIDS
(OVID Available online 2002)
卷期:
Volume 16,
issue 14
页码: 1867-1876
ISSN:0269-9370
年代: 2002
出版商: OVID
关键词: AIDS;cerebrospinal fluid;highly active antiretroviral therapy;HIV;HIV-1 RNA
数据来源: OVID
摘要:
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.
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