Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

The prevalence and outcomes of depression in older HIV-positive adults in Northern Tanzania: a longitudinal study.

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ2: 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p < 0.001), and increased functional impairment (p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

HIV-Associated Neurocognitive Disorders: The First Longitudinal Follow-Up of a cART-Treated Cohort of Older People in Sub-Saharan Africa.

BACKGROUND: HIV-associated neurocognitive disorders (HAND) are a highly prevalent chronic complication in older people living with HIV (PLWH) in high-income countries. Although sub-Saharan Africa has a newly emergent population of older combination antiretroviral therapy (cART)-treated PLWH, HAND have not been studied longitudinally. We assessed longitudinal prevalence of HAND and have identified possible modifiable factors in a population of PLWH aged 50 years or older, over 3 years of follow-up. METHODS: Detailed neuropsychological and clinical assessment was completed annually in the period 2016-2019 in a systematic sample of cART-treated PLWH in Kilimanjaro, Tanzania. A consensus panel defined HAND using American Academy of Neurology criteria for asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia. HIV disease severity and other factors associated with HAND progression, improvement, and stability were evaluated in individuals fully assessed at baseline and in 2019. RESULTS: At baseline, 47% of the cohort (n = 253, 72.3% female individuals) met HAND criteria despite good HIV disease control [Y1 59.5% (n = 185), Y2 61.7% (n = 162), and Y3 57.9% (n = 121)]. Of participants fully assessed at baseline and year 3 (n = 121), HAND remained stable in 54% (n = 57), improved in 15% (n = 16), and declined in 31% (n = 33). Older age and lower education level significantly predicted HAND progression, whereas HIV-specific factors did not. Male sex and shorter cART duration were associated with improvement. CONCLUSIONS: In this first longitudinal study characterizing clinical course of HAND in older cART-treated PLWH in sub-Saharan Africa, HAND was highly prevalent with variable progression and reversibility. Progression may be more related to cognitive reserve than HIV disease in cART-treated PLWH.

Risk factors for symptomatic HIV-associated neurocognitive disorder in adults aged 50 and over attending a HIV clinic in Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorder (HAND), although prevalent, remains a poorly researched cause of morbidity particularly in sub-Saharan Africa (SSA). We aimed to explore the risk factors for HAND in people aged 50 and over under regular follow-up at a government HIV clinic in Tanzania. METHODS: HIV-positive adults aged 50 years and over were approached for recruitment at a routine HIV clinic appointment over a 4-month period. A diagnostic assessment for HAND was implemented, including a full medical/neurological assessment and a collateral history from a relative. We investigated potential risk factors using a structured questionnaire and by examination of clinic records. RESULTS: Of the cohort (n = 253), 183 (72.3%) were female and the median age was 57 years. Fifty-five individuals (21.7%) met the criteria for symptomatic HAND. Participants were at a greater risk of having symptomatic HAND if they lived alone [odds ratio (OR) = 2.566, P = .015], were illiterate (OR 3.171, P = .003) or older at the time of HIV diagnosis (OR = 1.057, P = .015). Age was correlated with symptomatic HAND in univariate, but not multivariate analysis. CONCLUSIONS: In this setting, HIV-specific factors, such as nadir CD4 count, were not related to symptomatic HAND. The "legacy theory" of early central nervous system damage prior to initiation of anti-retroviral therapy initiation may contribute, only in part, to a multifactorial aetiology of HAND in older people. Social isolation and illiteracy were associated with symptomatic HAND, suggesting greater cognitive reserve might be protective.