The Prevalence of Frascati-Criteria-Based HIV-Associated Neurocognitive Disorder (HAND) in HIV-Infected Adults: A Systematic Review and Meta-Analysis

Abstract

Background: The HIV associated mortality is decreasing in most countries due to the widespread use of antiretroviral therapy. However, HIV-associated neurocognitive disorder (HAND) remains a problematic issue that lowers the quality of life and increases the public health burden among people living with HIV. The prevalence of HAND varies across studies and selected samples. Therefore, we aimed to quantitatively summarize the pooled prevalence of Frascati-criteria-based HAND and to explore the potential demographic, clinical, and immunological factors.Methods: A comprehensive literature search in PubMed/Medline, Web of Science, Embase, and PsycINFO was performed. A random-effects meta-analysis was conducted using the event rate (ER) for the estimation of the incidence of HAND. Subgroup meta-analyses were used to evaluate between-group differences in categorical variables. Meta-regression with the unrestricted maximum likelihood (ML) method was used to evaluate associations of continuous variables.Results: Eighteen studies whose sample sizes ranged from 206 to 1555 were included in the final analyses. The estimated prevalence of HAND, ANI, MND and HAD were 44.9% (95% CI 37.4–52.7%), 26.2% (95% CI 20.7–32.7%), 8.5% (95% CI 5.6–12.7%), 2.1% (95% CI 1.2–3.7%), respectively. Factors associated with HAND were percent female, current CD4 count, education level and country development level (all ps < 0.05).Conclusion: Longitudinal cohort and multimodal neuroimaging studies are needed to verify the clinical prognosis and the underlying neurocognitive mechanism of HAND. In addition, it is urgently necessary to establish a standardized HAND diagnostic process.

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

“…This is consistent with Al-khindi et al (2011) and Habib et al (2013) reviews, which showed modest and substantial ART benefits in people living with HIV, respectively. However, this contrasts with recent studies that have shown no association between ART use and neurocognitive performance (Walker & Brown, 2018;Wei et al, 2020).…”

“…The global prevalence of HIV-associated neurocognitive impairment in the antiretroviral era is estimated at 43-45% (Wang et al, 2020;Wei et al, 2020). Varying prevalence rates have been reported in studies conducted in low-and middleincome countries in the range of 12-74% (Michael et al, 2020).…”

“…While the debate on prevalence estimates of HAND based on the Frascati criteria lingers, it is reassuring that most cases of HIV-associated neurocognitive impairment are asymptomatic (Gisslen et al, 2011;Nightingale et al, 2020). However, there are reports that income group of a country is associated with HIV-associated neurocognitive impairment (Robertson et al, 2011;Wei et al, 2020), especially as low-and middle-income countries grapple with poverty, political instability, gender-based violence, malnutrition, and poorly developed health and education infrastructure (Shao & Williamson, 2012). In addition to these socioeconomic factors, the clinical context of the HIV epidemic within lowand middle-income countries has further contributed to the high burden of HIV-associated neurocognitive impairment.…”

“…Treatment programs managed by national government institutions, donors, and non-governmental organizations drive the choice of regimens that are more convenient, affordable, and safe (World Health Organization, 2016). However, these regimens have varied pretreatment drug resistance, drug-drug interactions, side effects, central penetrating effectiveness (CPE), and neurotoxicity that impact neuropsychological performance (Cysique et al, 2011;Ndashimye & Arts, 2019;Wei et al, 2020). Before the migration toward a first-line Dolutegravir-based ART regimen in low-and middle-income countries, Efavirenz was the preferred non-nucleoside reverse transcriptase backbone (NNRTI) (Bednasz et al, 2019;World Health Organization, 2016.…”

“I can’t cope with multiple inputs”: Qualitative study of the lived experience of ‘brain fog’ after Covid-19

“…Moreover, examples such as HIV-associated neurocognitive dysfunction, which afflicts over 40% of people with chronic HIV infection [65], impairing learning, memory, attention, and executive function, suggests possible overlap across multiple chronic viral infections. A recent study in Nature illustrates how such higher order disruptions may be mediated on a molecular level through viral-associated perturbations in general cellular functions such as cortical excitatory synaptic signalling, choroid plexus disruption enabling peripheral T cell infiltration, and promotion of pathological microglial and astrocyte subpopulations [66].…”