Aims:This study was designed to evaluate the effects of Efavirenz-based highly active antiretroviral therapy (EFV b -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 EFV b -HAART (range 10-1200 mg) in the fly food for initial 7 days to determine the LD 50 , 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. Iorjiim et al.; JABB, 23(1): 26-38, 2020; Article no.JABB.54451 27 Results: The LD 50 of EFV b -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 EFV b -HAART in D. melanogaster. Our findings suggest that long term use of EFV b -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 EFV b -HAART in D. melanogaster with the view of ameliorating same. Original Research Article

Objective: This study intended to evaluate the toxic effects of Efavirenz-based highly active antiretroviral therapy (EFVb-HAART) on some antioxidant parameters, and free radical generation in D. melanogaster. Materials and Methods: The study was carried out at the Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria, in 2019. Sixty (60)                        D. melanogaster (both sexes) 1-4 days old were exposed by ingestion to graded concentrations of EFVb-HAART (93.11 mg, 46.56 mg, 23.28 mg, 11.64 mg) or 1000 mL distilled water (control) each per 10 g fly food for five days. All concentrations were diluted with 1000 mL distilled water and incorporated in cold fly food in five replicates. Treated flies were anesthetized under ice, homogenized, centrifuged, and the supernatant used to assay for Total protein, Total thiol, Glutathione-S-transferase, Catalase, Superoxide dismutase, and Malondialdehyde levels. Statistical significance was accepted at P< 0.05. Results: The result showed significantly (P<0.05) increased total protein (1.05±0.0 - 1.34±0.12 Vs. 0.56±0.14 mg/ml) and Malondialdehyde levels (1.63±0.20 – 3.72±0.53 Vs. 0.79±0.10 units/mg protein) in all tested groups versus unexposed. Conversely, Total thiol content (1.96±0.33-0.38±0.10 Vs. 5.31±0.31 units/mg protein) Glutathione-S-transferase (2.20±0.30-1.01±0.27 Vs. 4.31±0.24 units/mg protein), Catalase (171.70±50.13-104.34±9.56 Vs. 368.00±7.56 units/mg protein) and Superoxide dismutase (3.18±0.29-1.44±23 Vs. 5.34±1.35 units/mg protein) activities all decreased significantly (P<0.05) as concentrations increased in all test groups versus unexposed. Conclusion: Overall, our results suggest that the mechanism of EFVb-HAART toxicity involves sterile immune response observed as increased protein contents, oxidative stress evidenced by depleted oxidative stress-antioxidant parameters, and possible free radical generation shown by increased malondialdehyde levels. Human-based studies are required for deeper understanding of these EFVb-HAART toxicities.

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Background/Objective: Dolutegravir-based highly active antiretroviral therapy (DTG-HAART) is the preferred regimen in the management of HIV/AIDS. However, the reproductive and oxidative stress toxicity of DTG-HAART is unknown.  This study was designed to investigate the reproductive and oxidative stress toxicity of DTG-HAART in Drosophila melanogaster. Materials and Methods: We performed all the experiments at the Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria, in 2019.  D. melanogaster, (1-4 days old), were fed with ten different concentrations of DTG-HAART (range 15 mg -595 mg) or 1000 mL distilled water per 10 g food for seven days to calculate the LD50, then treated with 93.11 mg, 46.56 mg, 23.28 mg, 11.64 mg or 1000 µL distilled water each per 10 g fly food for five days in five replicates. Subsequently, longevity, fly fecundity, and negative geotaxis evaluated. Also, activities of Acetylcholinesterase, Glutathione-S-transferase, Superoxide dismutase, Catalase, as well as Total thiol, and Malondialdehyde levels were investigated in the whole fly homogenate. Statistical values at P<0.05 were considered significant. Results: The LD50 of DTG-HAART in D. melanogaster was 106.4 mg. The result showed significantly decrease (P<0.001) in mean lifespan, fly emergence, Total thiol content, Acetylcholinesterase, Glutathione-S-transferase, Catalase, and Superoxide dismutase activities in the exposed groups compared to the unexposed. Inversely, the Malondialdehyde level in the test groups was significantly (P<0.001) elevated compared to unexposed. Conclusion: Collectively, our results suggest that   DTG-HAART toxicity was associated with reproductive deficits and oxidative stress induction in D. melanogaster, here observed as reduced fly fecundity, mean lifespan, AChE activity, antioxidant parameters, and elevated MDA level. This study, thus, raised concerns for long term use of DTG-HAART by HIV patients.

Aim: To evaluate the longevity and ameliorative activities of Moringa oleifera leaf (MOL) extract against some HAART drug-induced toxicities in Drosophila melanogaster. Materials and Methods: The research was conducted at the Drosophila laboratory, Africa Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos-Nigeria, between August 2019 - March 2020.  D. melanogaster (1-3 day) were first exposed for life to different concentrations of MOL (50 – 500 mg) or 25 mM Ascorbic acid or 1000 µL distilled water to determine longevity. Secondly, flies were fed on 46.56 mg of HAART drugs (Efavirenz-based or Dolutegravir-based) alone or supplemented with MOL 250 mg or 500 mg per 10 g fly food in five replicates for seven days. Afterward, longevity, fecundity, and negative geotaxis were evaluated. Also, activities of Superoxide dismutase, Catalase, as well as Malondialdehyde content as biomarkers of oxidative stress were evaluated using whole fly homogenate. Statistical significance was taken at P<0.05 or (P<0.006) (Bonferroni adjusted P-value for multiple curve comparisons.  Results: The MOL extract significantly (P<0.001) increased fly longevity compared to control groups. Similarly, supplementation with 500 mg MOL extracts significantly (P<0.05) ameliorate HAART drug-induced deficits in climbing ability, fecundity, SOD, and CAT activities as well as MDA content compared to groups exposed to HAART drugs alone respectively. Conclusion: The results suggest that   M. oleifera leaf extract extends lifespan and ameliorate HAART drug-induced toxicities via its antioxidant activities. This was supported by improved locomotor and reproductive decline, and restoration of the deficits in the biomarkers of oxidative stress (SOD, CAT, and MDA) in D. melanogaster.