In contrast, they demonstrated stable parameters over 96 months in asymptomatic, untreated patients with HIV-1 infection [30]. The mechanisms of the effects of both the disease process and the use of HAART remain uncertain. Dysfunction of the accessory glands as a consequence of latent infection may reduce semen volume, or a direct viral effect on spermatogenesis or altered seminal plasma composition may affect sperm count and motility. Mitochondria provide the necessary adenosine triphosphate within sperm to maintain progressive motility. buy INCB018424 Some antiretrovirals may affect mitochondrial function by inhibition of mitochondrial DNA replication.

Several antiretrovirals (in particular nucleoside reverse transcriptase inhibitors) have been demonstrated to have mitochondrial toxicity, potentially impacting on sperm motility [31,32]. This theory is supported by the findings of a small PARP inhibitor study demonstrating an increased frequency of DNA deletions in the sperm of patients receiving HAART for more than 12 months [33]. Protease inhibitors have also been demonstrated to inhibit apoptosis with subsequent cell dysfunction and asthenozoospermia [34]. However, it may be that any potential deleterious effect of the medication is negated by the effect of improved

health on spermatogenesis. In conclusion, our data confirm the detrimental effect of HIV on semen parameters, with a negative correlation being found between CD4 cell count and semen parameters. We have also demonstrated the potential negative effect of the use (and increased duration of use) of HAART on sperm, which

may counteract the benefits of a reduction Dichloromethane dehalogenase in VL and an increase in CD4 cell count. Despite these significant findings, the correlation coefficients were low, suggesting a gradual effect, and even on HAART and at low CD4 cell counts the mean seminal parameters would be compatible with spontaneous conception and therefore suitable for IUI. It is therefore imperative that recommendations with regard to the management of HIV disease (e.g. timing of antiretrovirals) continue to be made on virological and clinical grounds rather than with a view to improving the outcome of fertility treatment. Disease control remains a paramount concern and appropriate management decisions should remain with the patient and genitourinary medicine physicians. This view is supported by our analysis of outcome data, which demonstrates that markers of HIV disease do not impact on outcome, with no difference in pregnancy or miscarriage outcome according to CD4 cell count, serum VL, or use or duration of use of HAART [35].