The relationship between mitochondrial function and retinal microvascular features in people living with HIV: findings from the MitoSAKen study

HIV infection and antiretroviral therapy have been associated with mitochondrial dysfunction and alterations in the retinal microvasculature. This study explored the relationship between mitochondrial function and retinal microvascular characteristics in people living with HIV (PLWH).

This cross-sectional study enrolled 104 adults [52 HIV-positive (HIV+) on ART and 52 HIV-negative (HIV-)] recruited from Worcester, Western Cape. Clinical, demographic, anthropometric data, blood and urine samples were collected. Mitochondrial function was measured in peripheral blood mononuclear cells using the Oroboros O2k system. Retinal images were ta

ken with a Canon CR-2 camera. Statistical analysis was conducted using SPSS Version 29.0 (p<0.05).

The cohort was relatively young (<40 years) and predominantly female (70%). Compared to the HIV- group, the HIV+ group showed reduced mean arteriolar diameters (µm) for the mother vessel [(AD0) 69.47±13.51 vs. 82.43±13.68, p<0.001], smallest daughter vessels [(AD1) 55.75±12.30 vs. 62.28±10.46, p=0.006], and largest daughter vessels [(AD2) 62.54±13.06 vs. 72.22±12.08, p<0.001]. Mean venular diameters were lower in the HIV+ group: mother vessel (106.68±14.13 vs. 116.47±23.29, p=0.012) and largest daughter vessel (90.94±13.19 vs. 99.09±19.78, p=0.017). Mitochondrial routine respiration (pmol/min/10⁶ cells/mL) was lower in the HIV+ group [Median (range): 0.00(0.00–5.77) vs. 2.66(0.00–8.05), p<0.001], and inversely associated with HIV status [Standardised β (95% CI): -0.724(-0.891 to -0.557), p<0.001]. HIV duration (>3 vs. ≤3 years) was independently associated with complex I-linked respiration [β: 0.581(0.016 to 1.146), p=0.044]. In the HIV+ group, cytochrome C response showed an inverse association with AD0 [β: -1.339(-2.149 to -0.530), p=0.002], AD1 [β: -1.583(-2.476 to -0.690), p<0.001], and AD2 [β: -1.536(-2.371 to -0.700), p<0.001].

Preliminary findings indicate PLWH have altered mitochondrial function (reduced routine respiration) and retinal vessel branching. Increased cytochrome c response, suggesting mitochondrial membrane damage, was linked to reduced retinal blood flow efficiency, highlighting retinal features as potential biomarkers of underlying mitochondrial dysfunction in PLWH.

Retinal vessel branching features