Semen mitochondrial DNA damage as a marker of nucleoside analogue toxicity: the effect of HAART on semen quality of HIV-1 infected men
     D Mital ¹ , JC St John ² , S Taylor ¹ , MJ Tomlinson ² and DJ White ¹ 1 Department of Sexual Medicine, Birmingham Heartlands Hospital, UK ² Reproductive Biology and Genetics Group, The Department of Medicine, The University of Birmingham, UK

Background:
Nucleoside reverse transcriptase inhibitors may cause side effects due to generation of abnormal mitochondrial (mt)DNA in selected tissues. Spermatogenesis may be particularly susceptible to mtDNA damage from cytoplasmic condensation. We used a novel technique to detect mtDNA deletions in sperm. We also examined semen quality in men on different antiviral regimens.

Methods:
10 HIV-1 positive men on various highly active antiretroviral therapy (HAART) regimens produced semen samples for quality and mtDNA analysis. One patient was followed intensively for 14 months. Sperm counts and motility analyses were by Hamilton Thorn Analyser. Semen mtDNA was isolated from frozen samples by Puregene DNA Isolation Kit and weighed by mass spectrophotometry. MtDNA deletions were detected by long-chain polymerase chain reaction. Testosterone and FSH levels were measured to exclude other possible causes of male infertility.

Results:
Significantly more patients treated for >12 months had mtDNA deletions than those treated for <12 months (4/4 vs 1/3 P<0.05, Fisher's exact test). These patients also had poor semen quality and three had clinically evident lipodystrophy; 4/5 treatment-naive patients showed no mtDNA deletions. The intensively followed patient had no mtDNA deletions and good semen quality at baseline but increasing multiple mtDNA deletions at 6 and 14 months. Semen quality changed as therapy altered. Testosterone and FSH were normal.

Conclusions:
Changes in semen quality can occur in patients commencing HAART and may be drug-specific. Semen mtDNA damage may be a marker of HAART-related toxicity such as lipodystrophy.