Antiretroviral Therapy in HIV Infection
The effect on neuropsychological function of antiretroviral drugs that are able to penetrate into the brain in effective concentration (neuroactive drugs) remains unclear. To investigate whether highly active antiretroviral therapy (HAART) containing neuroactive drugs is associated with better neuropsychological performance in patients with human immunodeficiency virus disease. Cross-sectional survey. Tertiary referral hospital outpatient clinics. The study population consisted of 97 individuals positive for human immunodeficiency virus (stage C3, 1993 Centers for Disease Control and Prevention classification) whose condition had been stable on their current HAART regimen for a mean +/- SD of 18.5 +/- 16.5 months and who were aged 48.14 +/- 9.38 years. The patient groups were analyzed according to whether their regimen contained 3 or more neuroactive drugs (neuroHAART group; n = 41) or not (HAART group; n = 56). Thirty seronegative men matched for age and education were recruited as controls. Neuropsychological performance on 7 cognitive domains. The neuroHAART and HAART groups did not differ from one another on neuropsychological performance, but both patient groups were impaired compared with controls. Impaired patients in each treatment group were compared, and the neuroHAART group showed significantly better memory performance, unrelated to plasma viral load, than the HAART group. No direct benefit of neuroactive HAART therapy was found in patients with advanced human immunodeficiency virus infection. However, in neuropsychologically impaired patients, there was a benefit in memory function. This suggests that a threshold of neuropsychological impairment is required for the benefit of neuroactive HAART.
[Show abstract] [Hide abstract] ABSTRACT: It is unknown if, compared to a triple drug antiretroviral therapy, boosted protease inhibitor monotherapy leads to worse results in specific neuropsychological processes. In our study, we included patients virologically suppressed (≥1 year), on antiretroviral therapy, without concomitant major neurocognitive confounders, receiving boosted lopinavir or darunavir as monotherapy (n = 96) or as triple therapy with two nucleoside reverse transcriptase inhibitors (n = 95). All patients underwent a comprehensive neuropsychological test battery (14 neuropsychological measures, covering seven domains). Both groups were compared in average score distributions and rates of neuropsychological deficits. Similar comparisons were conducted only for patients with neurocognitive impairment. In the adjusted analysis, we found only small differences between groups in the entire sample: better verbal learning (p = 0.02; d = 0.28) and verbal recall scores (p < 0.01; d = 0.25) in patients on boosted protease inhibitor monotherapy and slightly better motor skills with dominant hand (p = 0.02; d = 0.23) scores in patients on triple therapy. No greater proportion of deficits in the protease inhibitor monotherapy group was found in any neuropsychological measure. In neurocognitively impaired patients, we found similar outcomes in verbal learning, verbal recall, and motor skills with dominant hand but with larger effect sizes. Close similarities in the neurocognitive pattern between groups question the clinical relevance of the number of neuroactive drugs included in the regimen. These results also suggest that peripheral viral load control may be a good indicator of brain protection.0Comments 0Citations
- "Also in neurocognitively impaired patients, they found differences in verbal memory measures by treatment group but better performances was described in the group receiving more neuroactive drugs. Comparison with our results is difficult because only 55 % of Cysique et al. (2004) patients had undetectable plasma viral load. Besides, antiretroviral regimens and criteria to determine neurocognitive impairment were different. "
[Show abstract] [Hide abstract] ABSTRACT: We demonstrate for the first time that the genome-wide profiling of HIV-infected peripheral blood mononuclear cells (PBMCs) from HIV-patients free of neurologic disease show overrepresentation of neurodegenerative pathways (Alzheimer's, Parkinson's, ALS, Huntington's and Prion Disease, etc.) in genome-wide microarray analysis, which suggests that this genome-wide representation of neurodegenerative diseases-related pathways in PBMCs could possibly be a subcellular manifestation of neurologic interference by HIV. Further, the cell-tagging analysis attested this belief showing the large majority of genes tagged with cells of monocyte and macrophage lineage, which are implicated in neuronal dysfunction in both viral and non-viral neurodegenerative diseases. Together, these findings suggest that the genomic interference of HIV with neurodegenerative pathways is not by chance, but may be an early sign of HIV-mediated sub-genomic and sub-cellular manifestation of neurologic disease. Moreover, these findings signify the utility of PBMC and genome-wide mapping of the host gene expression as a powerful tool in predicting possible early events in neurologic deterioration in HIV patients.0Comments 4Citations
- "Functional alterations occur in both in central and peripheral nervous system. Despite the success of highly active antiretroviral therapy (HAART) at reducing the incidence of HIV-associated neurocognitive disorders (HAND), there are still nearly 50% HIV-infected individuals who are predisposed to multiple cognitive domain deficits, such as psychomotor slowing, attention, memory, working memory, executive function, abstraction, verbal fluency, speed of information processing, sensory perceptual, and motor speed , which eventually will translate into HIV-associated dementia in >25% of HIV+ individuals on HAART. So far, HAD remains to be one of the most devastating complications of HIV infection, which significantly interferes with the quality of life of HIV+ individuals. "
[Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy. Electronic supplementary material The online version of this article (doi:10.1007/s11682-011-9113-8) contains supplementary material, which is available to authorized users.0Comments 53Citations
- "HIV viral proteins are neurotoxic, so the volumetric differences found here may reflect neuronal loss, reduced dendritic complexity, synaptic loss (Wiley et al. 1991), and associated white matter degeneration. HAART medications often fail to significantly penetrate the blood brain barrier (Cysique et al. 2004), so brain atrophy may still occur in patients treated with antiretroviral medication. The MACS has previously shown that levels of viremia and CD4+ cell count predict the onset of HIV-Associated Dementia and neuropathy prior to the use of HAART (Childs et al. 1999). "