Metabolic dysfunction-associated steatohepatitis (MASH) is more common in people with HIV and associated with systemic inflammation and extrahepatic complications, including cognitive impairment. While cross-sectional studies suggest an association between MASH and worse cognitive outcomes, its impact on longitudinal cognitive trajectories in people with HIV remains unclear.
This prospective study included people with HIV aged≥50 years from HIV-NAT, Bangkok, Thailand, between 2015 and 2024. MASLD and MASH were identified at baseline using the FibroScan-AST (FAST) score. Cognitive function was assessed using the Thai-validated Montreal Cognitive Assessment (MoCA) at baseline and a follow-up visit. A multivariate linear mixed model was used to determine the difference in changes in MoCA scores between participants with and without baseline MASH.
Among 291 participants (60.5% male; median age 54.4 years), 60 (20.6%) met criteria for MASH at baseline. Over a median follow-up of 5.9 years, baseline MASLD was not associated with cognitive decline, whereas participants with baseline MASH showed a significantly greater cognitive decline between ages 50 and 80 years, after adjusting for age, sex, body mass index, education level, employment status, smoking, alcohol consumption, diabetes, hypertension, duration of HIV acquisition and exposure to efavirenz. Participants with MASH showed a mean MoCA decline of –4.79 (95% CI –7.49 to –2.09), compared with –0.94 (95% CI –2.20 to –0.32) among those without MASH (p-interaction = 0.007).
MASH is a significant predictor of steeper cognitive decline in older people with HIV, independent of traditional metabolic and HIV-related risk factors. These findings suggest that early identification and management of MASH may help mitigate cognitive decline in ageing HIV care.
Liver steatosis is increasingly recognized as a major comorbidity in people living with HIV (PLWH), with growing evidence suggesting an increased risk of progression to advanced liver disease. We assessed predictors of liver steatosis progression over 36 months in PLWH from low- and middle-income countries.
Between 2020 and 2023, we enrolled PLWH aged ≥40 years who had been on antiretroviral therapy (ART) for ≥6 months at nine HIV clinics in the IeDEA Sentinel Research Network (SRN) across the Asia-Pacific, the Americas and African IeDEA regions, and followed them prospectively for 36 months. Participants with available and reliable controlled attenuation parameter (CAP) measurements at both enrolment and the 36-month visits were included in the analysis. Steatosis progression was defined as incident steatosis (CAP ≥248 dB/m) or a transition to a higher steatosis grade (moderate ≥268 dB/m; severe ≥280 dB/m) among those with a lower steatosis grade at enrolment. Logistic regression was used to assess predictors of progression.
We included 923 participants (63% female; median age 50 years, interquartile range 45–55) in this analysis. At enrolment, 51% were overweight or obese, 10% had type 2 diabetes mellitus (T2DM), 94% had HIV RNA <1000 copies/mL and 72% were on integrase strand inhibitor (INSTI)-based ART. During the 36-month follow-up, 190 (20%) participants showed steatosis progression, including 147 (74%) with incident steatosis and 49 (26%) with worsening of steatosis grades. The progression rate was significantly higher in Asia-Pacific (33% [95% CI, 24−44]) and the Americas (36% [95% CI, 26−46]) compared to the African regions (17% [95% CI, 14−20]). Independent predictors of steatosis progression were overweight/obesity (aOR: 2.97, 95% CI: 2.03−4.40), T2DM (aOR: 2.41, 95% CI: 1.45−3.96) and dyslipidaemia (aOR: 1.46, 95% CI: 1.01−2.12). In females, INSTI use for ≥2 years at enrolment was additionally associated (aOR 3.19, 95% CI: 1.35−8.01).
Metabolic disorders—including T2DM, overweight/obesity and dyslipidaemia—were associated with steatosis progression in PLWH in our cohort. These findings underscore the need for targeted monitoring and prevention strategies to address this significant public health issue.
Children exposed to HIV but uninfected (CHEU) number approximately 15.7 million globally. In Zambia, an estimated 56,000 CHEU are born annually, representing a substantial proportion of the national birth cohort. CHEU experience a higher risk of neurodevelopmental delay compared to their peers born HIV-unexposed. It is unknown whether the increased neurodevelopment delay burden of CHEU has been diminished by maternal combination antiretroviral therapy.
This prospective observational study analysed a subset of participants from the Zambian Infant Cohort Study (ZICS), which included 1500 pregnant women–infant dyads enrolled at a peri-urban hospital in Zambia. Infants aged 6−24 months were enrolled in a 1:1 ratio of CHEU to CHU and were followed for 18 months. Neurodevelopment was evaluated using the Malawi Developmental Assessment Tool (MDAT) at 6- and 18-month follow-ups. Anthropometrics, Caregiver-Reported Early Development Instruments assessments, eye-tracking and additional assessments were conducted at 6-, 12- and 18-month follow-ups. The primary outcomes were MDAT domain-specific Z-scores for gross motor, fine motor, language and social-adaptive. A series of regression models were fitted with MDAT domain-specific Z-scores as dependent variables, and CHEU versus CHU status as the primary independent variable. All models were adjusted for child birth year, age at assessment, sex, mother's age, education, household size and socioeconomic status.
Between March 2022 and October 2024, a total of 316 mother−infant pairs were enrolled in the study (CHEU, n = 155; CHU, n = 161). MDAT assessments at the 18-month follow-up were done for a total of 286 infants (139 CHEU [89.7%] and 147 CHU [91.3%]). The mean age at 18-month follow-up was comparable between CHEU and CHU (29.1 vs. 28.0 months, respectively). Mean MDAT Z-scores were comparable between CHEU and CHU for all domains, with adjusted mean differences in Z-scores of 0.00 (95% CI: −0.23, 0.23) for gross motor, 0.00 (95% CI: −0.28, 0.27) for fine motor, −0.10 (95% CI: −0.48, 0.28) for language and −0.01 (95% CI: −0.32, 0.30) for social-adaptive.
Neurodevelopmental outcomes at endline were comparable between CHEU and CHU across all the MDAT domains in this peri-urban Zambian cohort.
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