Journal of acquired immune deficiency syndromes (1999) · 2025
Gluteal Adipose Tissue Mitochondrial Respiration and Insulin Sensitivity in Pregnant South African Women Living With HIV on Tenofovir-Lamivudine-Dolutegravir.
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Madlala Hlengiwe P, Jao Jennifer, Roussos Georgia, Mendham Amy E, Myer Landon, Abrams Elaine, Geffen Hayli, Mukonda Elton, Modibedi Reneilwe, Odayar Jasantha, Matyesini Sandisiwe, Dugas Lara R, Goedecke Julia H, Catalano Patrick, McComsey Grace A, Gerschenson Mariana
Аннотация
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 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/m 2 ). 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 with HIV-seronegative women. At T1, WWH with > 6 months' TLD duration had a stronger association between electron transport system capacity and log-Matsuda (β = 0.55, P = 0.04) compared with HIV-seronegative women. Similar results were observed at T3 for electron transport system (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 with ≤ 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.
METHODS: South African WWH (n = 67) and HIV-seronegative women (n = 31) underwent a gluteal subcutaneous adipose tissue 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/m 2 ). 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 with HIV-seronegative women. At T1, WWH with > 6 months' TLD duration had a stronger association between electron transport system capacity and log-Matsuda (β = 0.55, P = 0.04) compared with HIV-seronegative women. Similar results were observed at T3 for electron transport system (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 with ≤ 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.