The percentage of motile sperm (sperm able to move spontaneously and independently) was reduced in a small cohort of men after beginning combination antiretroviral therapy, according to a Dutch study published in AIDS. None of the other parameters of semen quality were affected, and the researchers did not determine whether there was any effect on the fertility of the men studied.
With many HIV-positive or mixed-status couples wishing to conceive, reproductive health and safety issues for people with HIV have been receiving attention. However, only two studies to date have assessed the effects of antiretroviral therapy on male sperm quality.
In this study, researchers examined eight different parameters of semen from a prospective longitudinal cohort of HIV-positive men, before and during their first 48 weeks of antiretroviral therapy.
A total of 34 participants were recruited from the HIV outpatient clinic at the Academic Medical Centre in Amsterdam between February 2003 and October 2005. All were ART-naïve except for two who had taken antiretroviral therapy for less than eight weeks, two and three years previously. Apart from antiretroviral therapy use, exclusion criteria also included documented infertility.
The median age was 41; participants had been diagnosed HIV-positive for a median of 2.7 years; baseline CD4 cell counts were 230 cells/mm3 and viral load was 5.0 log10. Eleven (one-third) were smokers.
Baseline characteristics were recorded at the last clinic visit before antiretroviral therapy initiation; all participants then began a variety of first-line antiretroviral therapy regimens including both protease inhibitor- and NNRTI-based combinations.
Median follow-up was 48 weeks; a total of 146 semen samples (gathered at baseline, 4, 12, 24, 36, and 48 weeks post- antiretroviral therapy) were analysed for the following semen quality parameters: semen volume, spermatozoa concentration, percentage normally shaped spermatozoa, total sperm count, percentages of progressively motile (i.e., sperm with normal motility), slowly motile, and immotile spermatozoa, and the total motile count (TMC – the total number of progressively motile sperm).
Response to antiretroviral therapy was good, with mean CD4 cell increases from 276 to 428 cells/mm3 during follow-up, mean viral load decreasing from 5.0 to 2.1 log10, and 74% with viral load
The mean percentage of immotile sperm was high at baseline and all time points throughout follow-up – between 60% and 70%. The mean percentage of progressively motile sperm was low (28%) at baseline and decreased to 17% after 48 weeks (p = 0.02). (According to the World Health Organization (WHO), normal ranges are above 25% for progressively motile sperm, and below 50% for immotile sperm).
All other parameters were in WHO normal ranges and remained stable during antiretroviral therapy. Although motile sperm percentages were low, total motile count (TMC) remained above normal due to high overall sperm counts and concentrations. No significant associations were seen between semen quality parameters and CD4 cell count, viral load level, or use of thymidine analogues.
In this study of previously treatment-naïve HIV-positive men, 48 weeks of antiretroviral therapy "negatively affected the percentage of progressively motile spermatozoa", although other semen quality characteristics – including overall motile sperm count – were not affected. Whether this "affects the chance of fathering a child or leads to an increased need for artificial reproductive techniques is at present unknown."
In an accompanying editorial, Switzerland's Pietro Vernazza calls the results "remarkable," noting that due to the study design, "[all] possible confounders… [were] carefully ruled out."
Vernazza concurs with the researchers that nucleoside-associated mitochondrial toxicity could adversely affect sperm mitochondria: his own previous research has found weak associations between mitochondrial DNA content in sperm and exposure to didanosine and stavudine.
His editorial calls for further evaluation of mitochondrial toxicity in sperm and the relative effects of different drugs on sperm motility, and suggests that, if this study's clearly demonstrated results are confirmed, sperm motility could become "one of the most sensitive indicators of the toxicity of antiretroviral drugs."
References:
van Leeuwen E et al. Effects of antiretroviral therapy on semen quality. AIDS 2008;22:637-642.
Vernazza P. HAART improves quality of life: should we care about the quality of spermatozoa? AIDS 2008;22:747-648.