Toxicity of the Antiretrovirals Tenofovir Disoproxil Fumarate, Lamivudine, and Dolutegravir on Cyanobacterium Microcystis novacekii

Abstract

Antiretrovirals (ARVs) have become one of the most prescribed groups of drugs, and these residues are found in the environment. Among them, the most widely used in HIV treatment are tenofovir (TDF), lamivudine (3TC), and dolutegravir (DTG). This study aimed to evaluate the toxicity of ARVs TDF, 3TC, and DTG on the cyanobacterium Microcystis novacekii and estimate their environmental risk. DTG showed the highest toxicity among the drugs tested, inhibiting cyanobacteria cell growth and metabolic activity at low concentrations. TDF and 3TC alone were less toxic, with more pronounced adverse effects in long time exposures at high concentrations. However, the combination of ARVs, especially TDF and 3TC, showed a synergistic effect, significantly increasing toxicity compared to the drugs alone. Excipients found in commercial formulations of ARVs, such as sodium lauryl sulfate, also influenced toxicity. Although DTG showed the highest risk to cyanobacteria, the environmental risk assessment indicated that TDF and 3TC, although less toxic to M. novacekii, may pose moderate-to-high environmental risks at typical environmental concentrations. These results reinforce the need for strict regulation and monitoring of the release of ARVs into the environment, and the development of effective treatments for removing these residues in sewage treatment plants. This study contributes to understanding the ecotoxicological impacts of ARVs and highlights the importance of long-term assessments to adequately estimate the environmental risks of ARVs and their commercial formulations.