Antiretroviral therapy improves neurocognitive impairment in people living with HIV? A meta-analysis

Abstract

Objectives Although effective antiretroviral therapy (ART) has been used for more than two decades, HIV-associated neurocognitive disorder remains prevalent. Thus, whether ART can improve neurocognitive impairment is controversial. This review aims to explore the effects of ART on cognitive impairment in people living with HIV (PLWH). Methods A systematic literature search was conducted in eight databases (PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, China Biology Medicine disc, and WanFang) to identify studies that compare cognitive function between study groups who are administered and not administered ART. We searched for articles published up to April 2019. Article evaluation and data extraction were independently conducted by two reviewers. Results Sixteen articles (6,694 participants)—14 cross-sectional studies and 2 cohort studies—were included in this meta-analysis. The cross-sectional studies demonstrated that ART group did not perform better than the non-ART group ( OR = 1.16; 95% CI, 1.03–1.30). However, the cohort studies reported a significant improvement in cognitive function at three months ( OR = 4.01; 95% CI , 2.35–6.85) and six months ( OR = 9.24; 95% CI, 1.71–49.96) after ART initiation compared with the baseline data. No significant cognitive improvement was found in participants younger than 55 years old, but the two cross-sectional studies showed that ART may improve cognitive function in PLWH under 65 years old with poor physical condition and immune status. Conclusions ART could improve cognitive function in PLWH with poor physical condition and immune status, but it does not considerably improve cognition in the entire PLWH population.

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

“…Nadir CD4 was identified as a significant moderator of neurocognitive outcomes with antiretroviral therapy. This agrees with meta-analytic results by Al-khindi et al (2011) and Gao et al (2020) that showed a cognitive benefit of partial immune restoration on ART initiation in participants with advanced HIV infection and low immune status. However, the mean nadir CD4 across studies was low (209 cell/µl; SD = 112.5).…”

“…Our evaluation of probable sources of between-study heterogeneity using sub-group analysis identified design-related (between-groups vs. withingroup; cross-sectional vs. longitudinal) and methodological causes (use of normative scores). The subgroup of studies with a pre-and post-ART design showed significantly increased ART impact on cognitive outcomes compared to 2013) and Gao et al (2020). The marked difference in cognitive improvement with ART in cohort studies is most likely due to practice or retest effect due to familiarity with test content or familiarity with test environment and administrative personnel (Collie et al, 2003;Goldberg et al, 2015).…”

“…Age was not found to be a moderator of neurocognitive outcomes with ART. The effect of age in mediating treatment outcomes has been mixed (Al-Khindi et al, 2011;Gao et al, 2020). However, the mean age of participants across selected studies was below 50 years, which may have been responsible for the failure to identify statistical differences.…”

Identifying subtypes of HIV/AIDS-related symptoms in China using latent profile analysis and symptom networks

“…For cognitive symptoms, the findings are inconclusive regarding whether ART improves or increases cognitive impairment in PWH 40 , 41 . Gao and colleagues conducted a systematic review and found that ART did not improve cognitive function in the population of PWH, especially in PWH in moderate and good physical condition 42 . Paul summarized the neurocognitive phenotype of PWH taking ART and found that PWH had poor understanding and reasoning but no loss of memory after receiving ART 43 .…”

Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

“…In the case of ritonavir, it was found that it induces endoplasmic reticulum (ER) stress and mitochondrial outer-membrane permeabilization (MOMP) [ 40 ]. Finally, the data suggesting ART-mediated cognitive performance improvement is still controversial [ 38 , 41 , 42 ]; hence, some studies did not find a beneficial association, while Siangphoe et al [ 42 ] concluded in a meta-analysis that ART actually reduces the risk of developing neuronal disorders such as HAND. Nevertheless, the study did not include in the analysis the type of ART of each patient, which raises a question about if any specific antiretroviral or a combination of them is causing any neurocognitive deficit.…”