Exploring mitochondrial respiratory function in HIV-related cardiometabolic disease in a South African population

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.

Exploring whether a link exists between HIV-status, CMD and mitochondrial function in a study population from our city, South Africa.

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.

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), p<0.001], 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), p<0.001].

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.