Decrease of mitochondrial DNA level in sperm from patients infected with human immunodeficiency virus-1 linked to nucleoside analogue reverse transcriptase inhibitors

Abstract

Objective: To study sperm parameters in patients infected with human immunodeficiency virus (HIV)-1 and to analyze mitochondrial DNA (mtDNA) in sperm according to the HIV treatment.

Design: Observational study.

Setting: University-affiliated teaching hospital.

Patient(s): Thirty-two patients infected with HIV-1 and 31 noninfected healthy men provided semen samples.

Intervention(s): None.

Main outcome measure(s): After DNA extraction, mtDNA level was assessed using real-time polymerase chain reaction (PCR) (LightCycler) in whole semen and in selected spermatozoa from 90% density centrifugation gradients. For each sample, mtDNA and β-globin gene sequences were amplified and PCR products were quantified. The mtDNA-to-β-globin ratio expressed the number of mtDNA copies per cell.

Result(s): Compared with the control group, several sperm parameters were altered in patients with HIV. The number of mtDNA copies per cell in whole semen was increased in HIV-infected patients (6.3±6.3 vs. 3.5±3.2). However, there was no statistically significant difference in mtDNA copy number in the spermatozoa obtained after density gradient centrifugation. The number of nucleoside analogue reverse transcriptase inhibitors (NRTI) taken by patients during treatment significantly influenced the mtDNA level in sperm (1 NRTI 7.6±8.1, 2 NRTIs 7.0±5.1, 3 NRTIs 3.2±2.1).

Conclusion(s): Using a specific method to measure sperm mtDNA, we demonstrated a decrease of mtDNA copies in spermatozoa after use of NRTIs with known mitochondrial toxicity.