Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study

Goodkin, Karl; Miller, Eric N.; Cox, Christopher; Reynolds, S. R. M.; Becker, James T.; Martin, Eileen; Selnes, Ola A.; Ostrow, David G.; Sacktor, Ned

doi:10.1016/s2352-3018(17)30098-x

Cited by 102 publications

(81 citation statements)

References 31 publications

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“…We tested the effects of seven time invariant, binary predictor variable: Cohort (C1), Race (White), Confounding Conditions (Ever) [29], Hepatitis C Infection (Ever), Depression (Ever), HIV (Present), and AIDS (Present Ever). AIDS was defined as occurring when HIV seropositive men developed an AIDS-defined illness (i.e., ignoring CD4+ cell count).…”

Section: Methodsmentioning

confidence: 99%

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

Molsberry

Lecci

Kingsley

et al. 2015

Aids

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Objective The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the “closeness” of an individual to one of the canonical trajectories. Design The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV Disease among gay and bisexual men. Methods Using data from 3,892 men (both HIV-infected and uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual’s “closeness” to these trajectories. Results We identified three distinct trajectories to cognitive impairment – one “normal aging” (low probability of mild impairment until age 60), one “premature aging” (mild impairment starting at age 45–50), and one “unhealthy” (mild impairment in 20s and 30s) profile. Second, clinically defined AIDS and not simply HIV Disease, was associated with closeness to the premature aging trajectory. And, third, Hepatitis-C infection, Depression, Race, Recruitment Cohort and Confounding Conditions all affected individual’s closeness to these trajectories. Conclusions These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment.

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Section: Methodsmentioning

confidence: 99%

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

Molsberry

Lecci

Kingsley

et al. 2015

Aids

Self Cite

View full text Add to dashboard Cite

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“…These results from the MACS cohort have never been replicated, probably because particularly healthy individuals were selected and many without any evidence of HAND in the first place. Overall, this overview demonstrates that standardization of the definition of cognitive decline is urgently needed, especially as the HIV population is aging with an increased prevalence of age-related comorbidities (Guaraldi et al, 2011 ), and risk for brain premature aging (Brew & Cysique, 2017 ; Goodkin et al, 2017 ).…”

Section: Longitudinal Neuropsychological Profile: Global Naturalisticmentioning

confidence: 99%

HIV-Associated Neurocognitive Disorders: A Global Perspective

Saloner

Cysique

2017

J Int Neuropsychol Soc

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The present review on HIV-associated neurocognitive disorders (HAND) provides a worldwide overview of studies that have investigated the rate and neuropsychological (NP) profile of HAND research since the inception of the 2007 HAND diagnostic nomenclature. In the first part, the review highlights some of the current controversies around HAND prevalence rates. In the second part, the review critically assesses some solutions to move the field forward. In the third part, we present the cross-sectional NP profile in non-Western HIV+ cohorts and in relation to Western cohorts’ findings. The adopted global perspective highlights the successful expansion of NP studies in HIV infection to culturally diverse low- to medium-income countries with high HIV burden. These studies have produced interestingly similar rates of HAND whether patients were naïve or treated and/or virally suppressed compared to the rich income countries where the NP research in NeuroHIV has originated. The perspective also demonstrates that globally, the group which is the most representative of the HIV epidemic, and thus at risk for HAND are persons with chronic HIV infection and survivors of past immunosuppression, while in relative terms, those who have been treated early with long-term viral suppression represent a minority. In the last part, we present a review of the naturalistic longitudinal NP global studies in HIV+cohorts, discuss the role of longitudinal design in solving issues around the question of asymptomatic neurocognitive impairment, and the question of biomarker discovery. Finally, we conclude by calling for greater methods and data harmonization at a global level. (JINS, 2017, 23, 860–869)

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“…Despite these treatment benefits, HIV-suppressed patients remain at high risk of chronic diseases affecting gut, heart, and other tissues [ 4 , 5 ]. In the central nervous system (CNS), ART shifted HIV neuropathogenesis from the severe cognitive, psychiatric, and motor defects of dementia to milder chronic forms of neurocognitive impairment (HIV-NCI) that can disturb performance of everyday tasks and worsen with age [ 6 – 8 ] (reviewed in [ 9 , 10 ]]. Generally, chronic HIV morbidities are attributed to two factors, the persistence of replication competent HIV at low burdens within stable reservoirs of resting T lymphocytes [ 11 , 12 ] and secondarily, metabolic effects of some prolonged antiretroviral treatment [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment

et al. 2018

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Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

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Effect of ageing on neurocognitive function by stage of HIV infection: evidence from the Multicenter AIDS Cohort Study

Cited by 102 publications

References 31 publications

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study

HIV-Associated Neurocognitive Disorders: A Global Perspective

EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment

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