Mitochondrial dysfunction in CD4+ lymphocytes from stavudine-treated HIV patients

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Nucleoside analogue reverse transcriptase inhibitors (NRTI) like stavudine are widely used for HIV therapy in resource-limited settings.
• Potential adverse effects of NRTI on mitochondrial function, especially in peripheral blood lymphocytes (PBLs), are not fully understood.

Purpose of the Study:

• To investigate whether stavudine-based highly active antiretroviral therapy (HAART) is associated with impaired mitochondrial respiratory transport chain function in patient-derived CD4+ PBLs.

Main Methods:

• Isolated CD4+ PBLs from three groups: stavudine-HAART treated HIV patients (n=10), untreated HIV patients (n=9), and uninfected controls (n=18).
• Measured basal and maximal mitochondrial oxygen consumption using a respirometry assay.
• Assessed citrate synthase activity, mitochondrial volume (electron microscopy), and mtDNA copy number.

Main Results:

• Basal mitochondrial oxygen consumption was significantly reduced in CD4+ PBLs from stavudine-treated patients compared to untreated HIV patients and controls.
• Maximal oxygen consumption was also significantly lower in cells from stavudine-treated patients.
• No significant differences were observed in citrate synthase activity, mitochondrial volume, or mtDNA copy number between the groups.

Conclusions:

• Stavudine-based HAART leads to impaired mitochondrial function in CD4+ PBLs.
• This impairment is not due to reduced mitochondrial volume or DNA content.
• The observed mitochondrial dysfunction is attributable to stavudine therapy, not HIV infection.