EFVb-HAART Increases Mortality, Locomotor Deficits and Reduces Reproductive Capacity in Drosophila melanogaster

Aims: This study was designed to evaluate the effects of Efavirenz-based highly active antiretroviral therapy (EFVb-HAART, Efavirenz/Lamivudine/Tenofovir) with emphasis on survival, longevity, climbing ability, and reproductive capacity in D. melanogaster.

Methods: The experiments were carried out at the Africa Center of Excellence in Phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria between January 2017 and August 2018. D. melanogaster (both sexes) 1-4 days old were exposed to different concentrations of EFVb-HAART (range 10-1200 mg) in the fly food for initial 7 days to determine the LD50, then 5 day fly exposure to 93.11 mg, 46.56 mg, 23.28 mg or 11.64 mg for negative geotaxis assay, and acetylcholinesterase (AChE) activity. Furthermore, 28-day fly survival and longevity were determined. Statistical significance was presumed at P< 0.05.

Results: The LD50 of EFVb-HAART in D. melanogaster was 93.11 mg. The HAART exposed flies showed significantly (P<0.001) increased mortality, significant (P<0.001) decreased fly eclosion, acetylcholinesterse (AChE) activity and climbing ability compared to unexposed group at all experimental concentrations.

Conclusion: The decreased 28-day survival, longevity, climbing ability and reproductive capacity at all experimental concentrations may be attributable to the deleterious effects of EFVb-HAART in D. melanogaster. Our findings suggest that long term use of EFVb-HAART by HIV patients may be associated with accelerated aging, decreased life expectancy, quality of life (due to possible neurotoxicity) and reproductive competence, as evidenced by increased mortality, reduced longevity, AChE activity, and 100% emergence failure respectively in D. melanogaster, and may require further study in humans. We recommend further research to expound the biochemical and molecular toxicodynamics of EFVb- HAART in D. melanogaster with the view of ameliorating same.