<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The combination of antiretroviral (ARV) drugs: lamivudine, tenofovir disoproxil fumarate (TDF) and efavirenz is among the preferred first-line regimens for adolescents and adults infected with HIV. However, knowledge on <italic>in vivo</italic> genetic and reproductive toxicity of each of these drugs and their combination is limited. We evaluated the genotoxicity of lamivudine, TDF, efavirenz and their combination utilizing the mouse micronucleus (MN) and sperm morphology tests. Histopathological analysis of the testes of exposed mice was also carried out. 0.016, 0.032, 0.064 and 0.129 mg/kg bwt of lamivudine, TDF and the combination; and 0.032, 0.064, 0.129 and 0.259 mg/kg bwt of efavirenz corresponding to 0.125, 0.250, 0.500 and 1.000 x the human therapeutic daily dose (HTD) of each of the ARVs and their combinations were administered to mice for 5 consecutive days. Data on MN showed a significant increase (p &lt; 0.05) across the tested doses of TDF, efavirenz and the combination, with the combination inducing lower frequency of MN than TDF and efavirenz. Lamivudine did not evoke significant induction of MN. Significant increase in frequency of abnormal sperm cells were observed in the tested samples, however, the combination induced the highest number of abnormal spermatozoa. The ARVs and their combination induced pathological lesions such as vacuolation and necrosis in mice testes. These findings suggest that the individual ARVs and their combination are potentially capable of activating genetic alterations in the bone marrow and germ cells of male mice thereby raising concern for long term use by HIV patients.</p></abstract>

The combination of antiretroviral (ARV) drugs: lamivudine, tenofovir disoproxil fumarate (TDF) and efavirenz is among the preferred first-line regimens for adolescents and adults infected with HIV. However, knowledge on in vivo genetic and reproductive toxicity of each of these drugs and their combination is limited. We evaluated the genotoxicity of lamivudine, TDF, efavirenz and their combination utilizing the mouse micronucleus (MN) and sperm morphology tests. Histopathological analysis of the testes of exposed mice was also carried out. 0.016, 0.032, 0.064 and 0.129 mg/kg bwt of lamivudine, TDF and the combination; and 0.032, 0.064, 0.129 and 0.259 mg/kg bwt of efavirenz corresponding to 0.125, 0.250, 0.500 and 1.000 x the human therapeutic daily dose (HTD) of each of the ARVs and their combinations were administered to mice for 5 consecutive days. Data on MN showed a significant increase (p < 0.05) across the tested doses of TDF, efavirenz and the combination, with the combination inducing lower frequency of MN than TDF and efavirenz. Lamivudine did not evoke significant induction of MN. Significant increase in frequency of abnormal sperm cells were observed in the tested samples, however, the combination induced the highest number of abnormal spermatozoa. The ARVs and their combination induced pathological lesions such as vacuolation and necrosis in mice testes. These findings suggest that the individual ARVs and their combination are potentially capable of activating genetic alterations in the bone marrow and germ cells of male mice thereby raising concern for long term use by HIV patients.

Genetic and reproductive toxicity of lamivudine, tenofovir disoproxil fumarate, efavirenz and their combination in the bone marrow and testicular cells of male mice

Cell Biology and Genetics Unit, Department of Zoology

Department of Environmental Health, College of Medicine

Department of Anatomy, College of Medicine

Annals of Science and Technology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The combination of antiretroviral (ARV) drugs: lamivudine, tenofovir disoproxil fumarate (TDF) and efavirenz is among the preferred first-line regimens for...

Genetic and reproductive toxicity of lamivudine, tenofovir disoproxil fumarate, efavirenz and their combination in the bone marrow and testicular cells of male mice

Published Online: Jul 06, 2020

Page range: 1 - 10

Received: Oct 04, 2019

Accepted: Dec 23, 2019

DOI: https://doi.org/10.2478/ast-2020-0001

Keywords
HIV, Antiretroviral drugs, DNA damage, micronucleus, sperm morphology

© 2020 Adekunle A. Bakare et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Genetic and reproductive toxicity of lamivudine, tenofovir disoproxil fumarate, efavirenz and their combination in the bone marrow and testicular cells of male mice

Published Online: Jul 06, 2020

Page range: 1 - 10

Received: Oct 04, 2019

Accepted: Dec 23, 2019

DOI: https://doi.org/10.2478/ast-2020-0001

KeywordsHIV, Antiretroviral drugs, DNA damage, micronucleus, sperm morphology

© 2020 Adekunle A. Bakare et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
HIV, Antiretroviral drugs, DNA damage, micronucleus, sperm morphology