Antiretroviral Therapy in HIV Infection

Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
JAMA Neurology (Impact Factor: 7.42). 12/2004; 61(11):1699-704. DOI: 10.1001/archneur.61.11.1699
Source: PubMed


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.

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    • "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. "
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    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.
    Journal of NeuroVirology 04/2014; 20(4). DOI:10.1007/s13365-014-0251-9 · 2.60 Impact Factor
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    • "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 [1], 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. "
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    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.
    Virology Journal 12/2012; 9(1):308. DOI:10.1186/1743-422X-9-308 · 2.18 Impact Factor
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    • "Another explanation that we cannot definitively exclude and that may be one of the most plausible in the context of chronic HIV infection is that there is ongoing viral replication in the CNS despite maximal viral suppression in the plasma, due to increasing CNS compartmentalization with advanced HIV infection (Cunningham et al. 2000; Letendre et al. 2009). Still, in our cohort, the regimens with the highest CPE were observed in both VS groups, and they have been shown to efficiently reduce HIV RNA in the CSF compartment at least 1 year after initiation (Cysique et al. 2004a). "
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    ABSTRACT: HIV-associated neurocognitive disorder is known to occur in the context of successful combination antiretroviral therapy (cART; plasma HIV RNA <50 copies/ml). Here, we newly provide an analysis of its prevalence and nature in the absence of medical or psychiatric confounds that may otherwise inflate the prevalence rate. We enrolled a cohort of 116 advanced HIV + individuals on cART (51% virally suppressed (VS)). They were screened for active Hepatitis C, current substance use disorder and were assessed with standard neuropsychological (NP) testing. Our results showed that out of the entire sample, NP impairment occurred in 18.1% (21/116) in VS individuals which was not statistically different from the 24.1% (28/116) that were found to be NP-impaired and not VS. In comparison with NP-normal-VS persons, NP impairment in VS individuals was associated with shorter duration of current cART and lower pre-morbid ability. Higher cART CNS penetration effectiveness tended to be associated with lesser cognitive severity in NP-impaired VS individuals. Current CD4 cell count, depression symptoms and past CNS HIV-related diseases did not specifically account for persistent NP impairment in VS individuals. In conclusion, despite suppression of systemic viral load, non-confounded HIV-related NP-impairment prevalence reached 18.1%. Of the potential explanations for this persistent deficit, a "burnt-out" form of the disease and immune reconstitution inflammatory syndrome were the less likely explanations, while a shorter current cART duration and lower pre-morbid intellectual capacity were significant. Nonetheless, predictive modelling with these last two factors misclassified 27% and had low sensitivity (43%) emphasising that other yet-to-be-defined factors were operative.
    Journal of NeuroVirology 03/2011; 17(2):176-83. DOI:10.1007/s13365-011-0021-x · 2.60 Impact Factor
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