Effect of in vitro exposure of first-line antiretrovirals on healthy human spermatozoa on kinematics and motility

Abstract

Purpose: Contemporary antiretroviral (ARV) medications are used by millions of men for HIV treatment worldwide. Limited data exist on their direct effect on sperm motility. This pilot study hypothesizes that in vitro exposure to ARVs will reduce sperm kinematic and motility parameter values.

Methods: This laboratory-based experimental study analyzed sperm motility and kinematics after exposure to the ARVs Dolutegravir, Tenofovir, and Emtricitabine, individually and in combination. Each participant (n = 23) served as their experimental control. The Microptic SCA® Computer Assisted Sperm Analysis (CASA) system, Barcelona, Spain was used to generate quantitative data on sperm motility and the kinematics Straight-line velocity (VSL), Straightness index (STR), Linearity Index (LIN), Beat cross frequency (BCF), and the oscillation index (WOB).

Results: VSL, STR, LIN, and WOB of the non-progressive (grade c) spermatozoa were significantly decreased after ARV treatment. BCF of the medium velocity progressive sperm population (grade b) was significantly increased 90 min after exposure in the Tenofovir arm, and a significant decrease in the proportion of grade b spermatozoa was recorded at 90 min in all the antiretroviral arms when compared to the control arm. No impaired sperm motility was observed within the first 30 min of exposure.

Conclusion: Pharmacovigilance is a healthcare emergency as the fast-changing world of newer drugs leaves clinicians vulnerable. They must prescribe drugs whose long-term somatic and germline adverse effects are not fully understood. Guidelines and drugs are changing faster than we can monitor for side effects. Despite Dolutegravir being the only mainstream integrase inhibitor first-line ARV in South Africa for five years, its replacement, Cabotegravir, is already being launched. More research in this field is required, especially for commonly prescribed drugs. This preliminary pilot study concludes that the current first-line ARVs used by HIV patients and HIV-negative patients on pre-exposure prophylaxis (PrEP) can alter sperm motility and kinematics. Further research with a larger sample size is warranted to quantify its impact on human fertility, addressing the limitations of this study, before a comprehensive conclusion of the effects of ARVs on human male fertility can be drawn. Of particular importance would be to study the impact of ARVs on reactive oxygen species levels in semen and sperm DNA fragmentation.

Keywords: Antiretrovirals; Dolutegravir; Emtricitabine; Male infertility; Sperm kinematics; Sperm motility; Tenofovir.

Fig. 1

Flow diagram summarizing the workflow that was followed during this study. DTG Dolutegravir, TFV Tenofovir, FTC Emtricitabine, ARVs Antiretrovirals

Fig. 2

Diagram demonstrating CASA parameters. VCL curvilinear velocity, VAP average path velocity, VSL Straight-line velocity, ALH Amplitude of lateral head displacement

Fig. 3

Example of spermiogram capture of observations for participant S19’s Dolutegravir exposure arm at 0 min

Fig. 3

Example of spermiogram capture of observations for participant S19’s Dolutegravir exposure arm at 0 min