Article

CHARTER Group: HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study

University of California, San Diego, USA.
Neurology (Impact Factor: 8.29). 12/2010; 75(23):2087-96. DOI: 10.1212/WNL.0b013e318200d727
Source: PubMed

ABSTRACT

This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART).
A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment).
Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups).
The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.

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    • "The CNS is a critical site that must be studied when considering the use of LRA, as it has several unique characteristics that could greatly affect the outcome in the use of LRA. These include, but are not limited to, the potential to develop HIV-associated neurocognitive disorders (HAND) (Gonzalez-Scarano and Martin-Garcia 2005; Heaton et al. 2010); altered immune surveillance which may compromise the Bkill^ once virus is reactivated (Carson et al. 2006); restricted cART penetration into the CNS with some regimens which may lead to incomplete blocking of all new rounds of infection (Letendre et al. 2008); restricted LRA penetration into the CNS which may limit the ability to Bshock^ cells (Churchill et al. 2015); phylogenetically distinct HIV-1 within the CNS which may respond differently to LRA (Ait-Khaled et al. 1995; Gray et al. 2013a); and finally, unique long lived infected cells in the CNS including macrophages, microglia, and astrocytes (Kramer-Hammerle et al. 2005). "
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    ABSTRACT: Since the introduction of combination antiretroviral therapy (cART), the incidence of severe HIV-associated neurocognitive impairment has declined significantly, whereas the prevalence of the milder forms has increased. Studies suggest that better distribution of cART drugs into the CNS may be important in reducing viral replication in the CNS and in reducing HIV-related brain injury. Correlates of neuropsychological (NP) performance were determined in 417 participants of the Ontario HIV Treatment Cohort Study (OCS). All participants were on three cART drugs for at least 90 days prior to assessment. Multiple logistic and linear regression methods were used. Most participants were Caucasian men with mean age of 47 years. About two thirds had a nadir CD4+ T-cell count below 200 cells/μL and 92 % had an undetectable plasma HIV viral load. The median CNS penetration effectiveness (CPE) score was 7. Sixty percent of participants had neuropsychological impairment. Higher CPE values significantly correlated with lower prevalence of impairment in bivariate and multivariate analyses. In this cross-sectional analysis of HIV+ adults who had a low prevalence of comorbidities and were taking three-drug cART regimens, greater estimated distribution of cART drugs into the CNS was associated with better NP performance.
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    • "HIV-1 can cause neurocognitive impairment in infected individuals , even among those taking effective antiretroviral therapy (ART) (Heaton et al. 2010). The underlying mechanisms by which HIV-associated neurocognitive disorder (HAND) develops are not fully understood, but HAND has been associated with infecting HIV-1 subtype, nadir and current CD4 + T cell count, diversity in HIV-1 proteins Env and Tat, and blood and cerebrospinal fluid (CSF) HIV RNA levels (Ellis et al. 2011; Kaul et al. 2001; Munoz-Moreno et al. 2008). "
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