Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients
- 1 September 2002
- journal article
- research article
- Published by Wolters Kluwer Health in AIDS
- Vol. 16 (14), 1867-1876
- https://doi.org/10.1097/00002030-200209270-00003
Abstract
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. A cross-sectional and longitudinal study. Consecutive paired CSF and plasma samples from HIV-1-infected patients were collected before starting or changing highly active antiretroviral therapy (HAART). 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. 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
This publication has 33 references indexed in Scilit:
- Neurological Symptoms during Primary Human Immunodeficiency Virus (HIV) Infection Correlate with High Levels of HIV RNA in Cerebrospinal FluidClinical Infectious Diseases, 2000
- Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replicationAIDS, 1999
- Cerebrospinal Fluid Viral Load in HIV-1-Infected Patients Without Antiretroviral TreatmentJAIDS Journal of Acquired Immune Deficiency Syndromes, 1998
- Cerebrospinal fluid HIV-1 RNA levelsAIDS, 1998
- Relationship between human immunodeficiency virus—associated dementia and viral load in cerebrospinal fluid and brainAnnals of Neurology, 1997
- Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage.The Journal of Infectious Diseases, 1997
- Diagnosis of AIDS-related focal brain lesionsNeurology, 1997
- HIV‐1 DNA in brains in AIDS and pre‐AIDS: Correlation with the stage of diseaseAnnals of Neurology, 1996
- Neuropathology of Early HIV‐1 InfectionBrain Pathology, 1996
- Temporal trends in the incidence of HTV‐1‐related neurologic diseasesNeurology, 1994