Neuropathogenesis of HIV: From Initial Neuroinvasion to HIV-Associated Neurocognitive Disorder (HAND)

Zayyad, Zaina; Spudich, Serena

doi:10.1007/s11904-014-0255-3

Cited by 163 publications

(126 citation statements)

References 83 publications

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“…It is not known to what extent this early seeding of virus in the CNS leads to later development of cognitive dysfunction. However, it is likely that both ‘autonomous’ infection within the CNS compartment progressing from early seeded virus, and ‘transitory’ infection from recurrent seeding into the CNS throughout the course of chronic HIV disease, contribute to the pathogenesis of HAND (Rausch and Davis 2001; Zayyad and Spudich 2015). Early irreversible damage to the CNS, a legacy event, is thought to be partly responsible for the persistence of HAND in this era of cART (Brew and Chan 2014).…”

Section: Discussionmentioning

confidence: 99%

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria

et al. 2018

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Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria. A total of 179 HIV-1 infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study. Blood samples from participants were used for the measurement of plasma HIV RNA and CD4+ T cell count. Utilizing demographic and practice effect adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS ≥ 0.5 indicating cognitive impairment. In a longitudinal multivariable linear regression analysis, adjusting for CD4 cell count, Beck’s depression score, age, gender, years of education, and antiretroviral treatment status, global T scores decreased by 0.35 per log10 increase in Plasma HIV RNA [p=0.033]. Adjusting for the same variables in a multivariable logistic regression, the odds of neurocognitive impairment were 28% higher per log10 increase in plasma HIV RNA (OR: 1.28 [95% CI: 1.08, 1.51]; p=0.005). There were statistically significant associations for the speed of information processing, executive and verbal fluency domains in both linear and logistic regression analyses. We found a significant association between plasma HIV RNA levels and cognitive function in both baseline (cross-sectional) and longitudinal analyses. However, the latter was significantly attenuated due to weak association among antiretroviral-treated individuals.

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Section: Discussionmentioning

confidence: 99%

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria

et al. 2018

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“…4 While neurologic injury is not detected in the CSF immediately following infection, it develops in a subset of individuals during the first year 5–8 and correlates with neuroinflammation. 6 Persistent inflammation fostered by a cytokine milieu generated by activated microglia and astrocytes is hypothesized to lead to neuronal injury.…”

Section: Introductionmentioning

confidence: 99%

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection

Peluso

Valcour

Phanuphak

et al. 2017

Aids

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Objective To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. Design Cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. Methods AHI (n=33) and CHI (n=34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow up on cART in a subset of these individuals (6 months in AHI participants [n=24], 1 year in CHI participants [n=10]). Measured parameters were analyzed at each timepoint. Analyses employed Mann-Whitney tests and Spearman correlations. Results Baseline median YKL-40 was higher in CHI than AHI (96844 versus 80754 ng/L; p=0.011). Elevations in the CHI group relative to the AHI group persisted at follow-up despite treatment (87414 versus 66130 ng/L; p=0.003). In untreated CHI, YKL-40 correlated with neopterin (r=0.51, p=0.0025), chemokine (CXC-motif) ligand-10 (r=0.44, p=0.011), and neurofilament light chain (r=0.56, p=0.0008) in CSF. Conclusions This study is the first to describe the dynamics of CSF YKL-40 in two groups of HIV-infected individuals before and after cART and demonstrates the value of this marker in understanding HIV neuropathogenesis. The results suggest the utility of further exploring the prognostic value of YKL-40, particularly in individuals with early HIV infection or those initiating treatment during CHI.

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“…The central and peripheral nervous system (CNS and PNS) are directly impacted by HIV-1, likely through underlying effects of viral and immune factors(Zayyad & Spudich, 2015). …”

Section: Introductionmentioning

confidence: 99%

International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271

Robertson¹,

Jiang

Evans

et al. 2016

J. Neurovirol.

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Summary ACTG A5271 collected neurocognitive normative comparison test data in 2400 at-risk HIV seronegative participants from Brazil, India, Malawi, Peru, South Africa, Thailand and Zimbabwe. The participants were enrolled in strata by site (10 levels), age (2 levels), education (2 levels), and gender (2 levels). These data provide necessary normative data infrastructure for future clinical research and care in these diverse resource limited settings. Infrastructure for conducting neurological research in resource limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment, and normative data needed for clinical interpretation impede research and clinical care. Here we report on ACTG 5271, which provided neurological training of clinical site personnel, and collected neurocognitive normative comparison data in diverse settings. At 10 sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV- participants from Brazil (n=240), India (n=480), Malawi (n=481), Peru (n=239), South Africa (480), Thailand (n=240) and Zimbabwe (n=240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline, and 770 at six-months. Participants were enrolled in 8 strata, gender (female and male), education (<10 years and ≥ 10 years), and age (<35 years and ≥35 years). Of 2400 enrolled, 770 completed the six-month follow up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p<.0001). There was variation between the age, gender and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.

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Neuropathogenesis of HIV: From Initial Neuroinvasion to HIV-Associated Neurocognitive Disorder (HAND)

Cited by 163 publications

References 83 publications

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria

Plasma HIV RNA level is associated with neurocognitive function among HIV-1-infected patients in Nigeria

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection

International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271

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