J Acquir Immune Defic Syndr. 2025 Aug 26. doi: 10.1097/QAI.0000000000003755. Online ahead of print.
ABSTRACT
BACKGROUND: Mitochondrial dysfunction in adipose tissue is associated with diabetes pathophysiology. We examined this relationship in pregnant women with HIV (WWH) receiving tenofovir/lamivudine/dolutegravir (TLD).
METHODS: South African WWH (n=67) and HIV-seronegative women (n=31) underwent a gluteal subcutaneous adipose tissue (gSAT) biopsy at ≤ 14 weeks gestational age (GA) (Trimester 1, T1) and 28-37 weeks GA (T3). High-resolution respirometry was employed to measure mitochondrial respiration. Insulin sensitivity was calculated using the Matsuda index. Linear regression models were fit to examine effect modification by HIV status and TLD duration of the association between mitochondrial respiration and log-Matsuda.
RESULTS: At enrolment, WWH and HIV-seronegative women were similar in median age (28 years), GA (12 weeks), and body mass index (28 kg/m2). At T3, HIV infection was associated with higher Complex I-linked mitochondrial respiration (β=0.13, p=0.02). This association was more pronounced among WWH on TLD for ≤ 6 months (β=0.16, p=0.02) who also had higher Complex I+II-linked respiration (β=0.13, p=0.04) compared to HIV-seronegative women. At T1, WWH with > 6 months TLD duration had a stronger association between electron transport system (ETS) capacity and log-Matsuda (β=0.55, p=0.04) compared to HIV-seronegative women. Similar results were observed at T3 for ETS (β=1.05, p=0.03) and for a change score for leak (β=87.80, p=0.03) for > 6 months TLD duration compared to ≤ 6 months TLD duration.
CONCLUSIONS: HIV infection and longer TLD duration appear to be associated with stronger associations between mitochondrial respiration and insulin sensitivity, warranting further investigation into how HIV/TLD may influence glucose metabolism in adipose tissue.
PMID:40857048 | DOI:10.1097/QAI.0000000000003755
