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.
The statistical analysis was performed including patients taking the drugs for which we have a larger case number of plasma-CSF paired samples.
Antiretrovirals known to have high level of penetration in CSF or to effectively suppress HIV-RNA in CSF from literature reports, were considered “neuroactive drugs.” Among the antiretrovirals prescribed to the study patients, the neuroactive drugs included: zidovudine, stavudine, lamivudine, abacavir, nevirapine, efavirenz, indinavir, lopinavir [21
]. Lopinavir was always administered associated to a boost of ritonavir at recommended doses. Since indinavir was administered with or without the boost of ritonavir, boosted indinavir was considered as a different regimen from unboosted one.
Logistic regression was used to determine predictive factors of undetectable CSF viral load. Multivariable analysis was performed fitting three different models including variables related to antiretroviral therapy: in the first model the effect of each single drug included in the antiretroviral regimen was analyzed; in the second model the effect of different drug regimens was analyzed using the following categorization criteria: unboosted Protease Inhibitors PIs-, boosted PIs-, Non-Nucleoside-reverse-trascriptase-inhibitors- (NNRTIs-), NNRTIs-plus-PIs-, only-nucleoside-reverse-trascriptase-inhibitors- (NRTIs-) based regimens, or no therapy; in the third model the effect of the number of neuroactive drugs, as defined above, was analyzed. The Student t-test was employed to compare values of CSF HIV-RNA in different groups of patients (naïve-experienced, on HAART-no HAART). Correlation between log10 CSF HIV-RNA and number of neuroactive drugs was calculated using Pearson correlation coefficient r. All statistical analyses were performed by SPSS (version 11.0.1) for Windows (SPSS, Chicago, Illinois, USA). P values <0.05 were considered statistically significant.