Background:  There is evidence for mitochondrial (mt) damage from HIV itself and following therapy with nucleoside analogues (NRTI). NRTI-associated mt toxicity in children has varied clinical presentations but its pathogenesis has been scarcely investigated. We aimed to describe the mt function impairment in a series of vertically HIV-infected pediatric patients.

Methods:  A cross-sectional study of mtDNA content and mt respiratory chain function in peripheral blood mononuclear cells (PBMC) was performed in a series of HIV vertically infected pediatric patients; anonymous blood samples of children who were referred to our laboratory for presurgical routine blood analysis were used as a control group. MtDNA amount was assessed by real-time polymerase chain reaction (RT-PCR) and expressed as the ratio of mtDNA-encoded ND2 gene to r18s nuclear gene, while mt respiratory chain complex IV function and mitochondrial mass (estimated by cytrate synthase enzymatic activity), were measured by spectrophotometry. CIV activity was expressed in absolute values, as nmols oxidated substrate/minute/mg protein, and relative values by dividing absolute complex IV per mitochondrial mass. Subunits COXII and COXIV of complex IV, as well as mt content, were assessed by Western blot analysis.

Results:  Overall, 66 (34 girls, mean age 13.1 years) HIV-infected pediatric patients and 35 (20 girls, 12.5 years) healthy children were included; among the former, 47 patients were receiving HAART and 19 had interrupted therapy some time ago (range 3 months to 7 years) for a variety of reasons. Significantly lower mtDNA values were observed in HIV-infected patients when compared to controls (4.4 vs 5.8; p=0.005). This mtDNA impairment did not lead to differences between groups in mt respiratory chain function parameters: absolute and relative complex IV values, and subunits COXII and COXIV values. Among HIV-infected patients, no differences in mtDNA levels or mt respiratory chain function were observed when the use of HAART was taken into account. Similarly, no relationship was found between current CD4 cell counts, lactate levels or plasma HIV viral load and mtDNA.

Conclusions:  In this cross-sectional study, a reduction in peripheral blood mononuclear cells (PBMC) mtDNA content in HIV-infected children was observed. This depletion did not lead to mt respiratory chain function impairment. The use of HAART at the time of the study did not seem to interfere with mt parameters, although previous exposition to antiretrovirals in those patients who interrupted therapy probably represents a bias against these findings.