Research Article: Virological Response in Cerebrospinal Fluid to Antiretroviral Therapy in a Large Italian Cohort of HIV-Infected Patients with Neurological Disorders

Date Published: August 26, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Maria Letizia Giancola, Patrizia Lorenzini, Antonella Cingolani, Francesco Baldini, Simona Bossolasco, Teresa Bini, Laura Monno, Giovanna Picchi, Antonella d’Arminio Monforte, Paola Cinque, Valerio Tozzi, Andrea Antinori.


The aim of the present study was to analyse the effect of antiretroviral (ARV) therapy and single antiretroviral drugs on cerebrospinal fluid (CSF) HIV-RNA burden in HIV-infected patients affected by neurological disorders enrolled in a multicentric Italian cohort. ARVs were considered “neuroactive” from literature reports. Three hundred sixty-three HIV-positive patients with available data from paired plasma and CSF samples, were selected. One hundred twenty patients (33.1%) were taking ARVs at diagnosis of neurological disorder. Mean CSF HIV-RNA was significantly higher in naïve than in experienced patients, and in patients not taking ARV than in those on ARV. A linear correlation between CSF HIV-RNA levels and number of neuroactive drugs included in the regimen was also found (r = −0.44, P < 0.001). Low -plasma HIV-RNA and the lack of neurocognitive impairment resulted in independently associated to undetectable HIV-RNA. Taking nevirapine or efavirenz, or regimen including NNRTI, NNRTI plus PI or boosted PI, was independently associated to an increased probability to have undetectable HIV-RNA in CSF. The inclusion of two or three neuroactive drugs in the ARV regimen was independently associated to undetectable viral load in CSF. Our data could be helpful in identifying ARV regimens able to better control HIV replication in the CNS sanctuary, and could be a historical reference for further analyses.

Partial Text

One of the major concerns about antiretroviral (ARV) therapy is the question of whether current ARV regimens are effective in suppressing HIV-1 replication in the central nervous system (CNS) as well as in plasma. CNS is considered one of the anatomic reservoirs of HIV replication, sites in which the cellular HIV replication has a longer half-life [1, 2]. HIV dynamics in CNS and plasma can evolve independently, leading to virologic compartmentalization of HIV infection in the CNS [3]. It is well known that HIV can evolve and replicate in neurological compartment independently from plasma and the virological response in these two different compartments can be quite different [3–5]. Moreover, a residual HIV replication in CNS and persistent intrathecal immune activation can be detected also in patients on ARV [6, 7].

To analyse the effect of antiretroviral drugs, drug classes, and number of CNS-penetrating drugs on HIV-RNA load in CSF, a large group of HIV-infected patients affected by neurological disorders enrolled in the Italian Registry Investigative NeuroAIDS (IRINA) was studied. IRINA is a longitudinal, multicentric cohort study carried out in 45 Italian centres of infectious diseases, that since 2000 enrols HIV-infected patients affected by neurological disorders. In particular, the registry collects demographic and epidemiologic variables, natural history of HIV infection, antiretroviral therapy, clinical and radiological features, diagnostic criteria for neurological diagnosis, and virological and immunological parameters. Patients with paired CSF and plasma data available were included in the present study and were considered for the analysis. HIV-RNA levels in plasma and CSF were quantified by branched-DNA (Bayer, detection limit of 50 copies/mL, 1.69 log10), RT-PCR (Amplicor Roche Diagnostics, detection limit 50 copies/mL) or nucleic acid sequence-based amplification (NASBA) (Nuclisens HIV-1 QT assay Organon Teknika, detection limit of 80 (1.90 log10) copies/mL), depending on the assay used by each center. To account for the difference between NASBA and RT-PCR in HIV RNA quantification, values of HIV RNA by NASBA assay were divided by two. For the analysis, all HIV-RNA levels were transformed into log10 values. For the statistical analysis, CSF HIV-RNA were considered “undetectable” if the viral load was below the detection limit of the tool used.