Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster

Nucleoside reverse-transcriptase inhibitor (NRTI) drugs are a major component of highly-active antiretroviral therapy (HAART). NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count, thereby showing clear clinical benefits. Therefore, the secondary effects caused by the combination of two NRTIs, mainly those related to amplification of genotoxic effects, due to increased risk of DNA damage caused by these drugs, should be carefully examined. We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT + ddI, AZT + 3TC and AZT + d4T. Our results showed that all combinations increased the frequencies of induction of mutant spots. The combinations AZT + ddI and AZT + 3TC were shown to induce recombination rates ranging from 86.38% to 98.36% while AZT + d4T showed a large discrepancy between recombination and mutation percentages. The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT.

► All NRTI combinations increased the frequencies of induction of mutant spots. ► Mitotic recombination was the major event induced by AZT + ddI and AZT + 3TC. ► AZT + d4T showed a large discrepancy between recombination and mutation percentages. ► 3TC and d4T produced antagonism effects in combination with AZT. ► ddI showed synergistic effects in combination with AZT.