Abstract Background A significant proportion of people living with HIV (PLWH) present with mitochondrial impairment and cardiometabolic disease (CMD). However, the role of altered mitochondrial function in HIV-associated CMD remains unclear. Purpose Exploring whether a link exists between HIV-status, CMD and mitochondrial function in a study population from our city, South Africa. Methods Participants were divided into two main groups (HIV- and HIV+), that were further subdivided into HIV- with (n=39) and without (n=33) CMD, and HIV+ with (n=44) and without (n=42) CMD. Clinical and demographic data, and blood and urine samples were collected. CMD was defined as presenting with ≥3 cardiovascular risk factors. Mitochondrial function was assessed in isolated peripheral blood mononuclear cells by high-resolution respirometry. Results The cohort was relatively young (42 years) and consisted mostly of women (74.7%), with high smoking rates. Routine respiration (O2 consumption: pmol/s/mL) was significantly lower in the HIV+ group vs. HIV- 0.001(0.001-5.767) vs. 1.694(0.001-8.050), p0.001, whereas residual oxygen consumption (ROX) was higher in HIV+ vs. HIV- 0.312(0.001-6.330) vs. 0.157(0.001-4.798), p=0.036. The calculated cytochrome c response was supressed in HIV+ vs. HIV- 0.001(0.001-1.554) vs. 0.127(0.001-1.902), p=0.051. Maximal ETS capacity was significantly suppressed in CMD+ vs. CMD- 0.469(0.001-5.214) vs. 0.767(0.079-5.170, p=0.009. H2O2 production (μM) observed at complex IV activity was lower in HIV+ vs. HIV- 0.055(0.010-2.468) vs. 0.205(0.010-2.003), p0.001. Conclusion The findings of this exploratory study point to a greater degree of altered mitochondrial oxygen consumption and H2O2 production in people with HIV and CMD compared to their respective controls. Although changes were observed in both HIV+ vs. HIV- and CMD+ vs. CMD-, the results suggest that, overall, mitochondrial function was more profoundly affected by HIV-status. The findings pave the way for longitudinal studies with more diverse and larger cohorts, which may ultimately benefit the future management of PLWH at risk of mitochondrial dysfunction and CMD.
Webster et al. (Fri,) studied this question.