Antiretroviral Therapy in HIV Infection: Are Neurologically Active Drugs Important?

Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
JAMA Neurology (Impact Factor: 7.01). 12/2004; 61(11):1699-704. DOI: 10.1001/archneur.61.11.1699
Source: PubMed

ABSTRACT 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.

  • Source
    [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.
    Journal of NeuroVirology 04/2014; 20(4). DOI:10.1007/s13365-014-0251-9 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive impairment and neurodegeneration still occur despite highly active antiretroviral therapy (HAART). While there are many potential reasons for this, there is increasing evidence that such impairment occurs in the absence of a clear cause. Furthermore, there are data that some neurodegenerative diseases, especially Alzheimer's or an Alzheimer-like illness, are becoming more common in the context of HAART-treated human immunodeficiency virus (HIV) disease. This review will critically examine the evidence underpinning these observations. Potential mechanisms will be discussed with particular emphasis on the effect of ageing and how it overlaps with the effects of HIV disease itself thereby leading to neurodegeneration. The nature of this overlap will then be explored for its potential role in the facilitated expression and development of neurodegenerative diseases. Lastly, there will be a brief discussion of interventions to minimize such neurodegeneration including optimization of HAART for brain entry.
    Journal of Neuroimmune Pharmacology 06/2009; 4(2):163-74. DOI:10.1007/s11481-008-9143-1 · 3.17 Impact Factor