A Meta-Analytic Review of the Effect of Antiretroviral Therapy on Neurocognitive Outcomes in Adults Living with HIV-1 in Low-and Middle-Income Countries

Abstract

HIV-associated neurocognitive impairment remains a challenge even in the era of antiretroviral therapy (ART). Over 90% of people living with HIV are in low-and middle-income countries. Hence, it is not surprising that such countries bear a considerable burden of comorbidities like HIV-associated neurocognitive impairment despite an overall increase in life expectancy. The literature suggests differences in patient characteristics, clinical profile, prevalent HIV subtypes, treatment choices, pharmacogenetics, and socioeconomic factors between low-and middle-income countries compared with highincome countries. Therefore, we aimed to evaluate the effect of ART on neurocognitive outcomes in low-and middle-income countries. A comprehensive search of five databases (PubMed, CINAHL, CENTRAL, PsychInfo, Google scholar) for studies published between 1996 to 2020 was performed to identify studies that reported neurocognitive outcomes in ART-treated and ART naïve HIV positive individuals. Two independent reviewers conducted study screening, data extraction, and evaluation of the risk of bias. Pooled effect size estimates (Hedges' g) and 95% CI were computed using random-effects models. Sensitivity analysis, subgroup analysis, meta-regression, and evaluation of publication bias were also conducted. Forty studies (24 cross-sectional, 13 longitudinal studies, and two randomized controlled trials) contributed to a series of meta-analyses. We found significant small to moderate effects of antiretroviral therapy for global cognition (Hedges' g observed = 0.30; 95% CI: 0.15, 0.44; k = 25; p = 0.0003; I 2 = 92.1%; tau = 0.32; Q = 305.1), executive function (Hedges' g = 0.24, 95%CI: 0.02,0.46; p-0.04; k = 8; I 2 = 37.5%; tau = 0.23; Q = 11.2), and speed of information processing (Hedges' g = 0.25, 95% CI: 0.05, 0.45; k = 9; p = 0.02; I 2 = 86.4%; tau = 0.21; Q = 58.9). We found no significant ART effect on attention-working memory, learning and memory, motor function, and verbal fluency. No significant effect was seen with the duration of therapy, efavirenz use, and Central Penetrating Effectiveness (CPE) of antiretroviral therapy. Subgroup analyses identified study design (betweengroup and within-group; cross-sectional and longitudinal) and normative scores as significant sources of heterogeneity. Metaregression analysis indicated that nadir CD4 modified the magnitude of ART's effect on cognitive outcomes. Age, gender, and country income-group were not significant moderators. Our findings provide systematic evidence that antiretroviral therapy improves neurocognitive outcomes in the domains of global cognition, executive function and speed of information processing, of people living with HIV in low-and middle-income countries, especially those with advanced immunosuppression. However, these findings are not definitive as they are limited by the probability of publication bias, high heterogeneity, and exclusion of significant confounders. Prospero registration number: CRD42020203791.

Mental health and cognition in relation to adherence to antiretroviral therapy among people living with HIV in Kazakhstan: a cross‐sectional study

“…On the other hand, long-term exposure to ART medications can be associated with neurocognitive impairment [55,56]. The neurotoxic and neuropsychiatric impacts stemming from both the ART and the HIV infection itself necessitate a more comprehensive grasp of the pathological, pharmacological and behavioural mechanisms involved into the worsening of the cognitive function of PLWH [57][58][59][60].…”

Exploring Interrelationships between Mental Health Symptoms and Cognitive Impairment in Aging People Living with HIV in China

“…Several studies have been conducted to prevent or delay cognitive function decline, which found that HIV infection, comorbidities, non-adherence to antiretroviral therapy (ART), and mental health symptoms may be crucial risk factors for aggravating cognitive impairment in aging PLWH [4][5][6][7][8]. Among these factors, mental health symptoms are a modifiable risk factor for early intervention of HAND [9][10][11][12]. Furthermore, aging PLWH may suffer from mental health symptoms more than general aging people due to negative illness perception [13][14][15], which may further affect cognition-related behavior such as non-adherence to ART [16,17].…”