Chemokine Antagonists(Evolutec Group Plc)

The antiretroviral therapy program's success in managing the human immunodeficiency virus (HIV) has inadvertently led to the release of antiretrovirals (ARVs) into worldwide aquatic ecosystems. However, few studies investigated the risks of ARV loadings that flow continuously to the marine waters of South America (such as Brazil). Against this backdrop, the aims of this study were: (i) to estimate the Predicted Environmental Concentration (PEC) of thirteen ARVs worldwide used in HIV treatment, and which are frequently disposed of in the marine aquatic ecosystems of Guarujá, São Paulo coastline, Brazil.; (ii) predict, through the Environmental Risk Assessment (ERA), the potential acute and chronic risks of these ARVs; and (iii) create a prioritization list of the most hazardous ARVs, based on the intrinsic properties of these compounds, i.e.: occurrence (O); persistence (P), bioaccumulation (B) and toxicity (T) (OPBT criteria). The PEC calculations indicated that all the ARVs examined in this study require an assessment of their impact on aquatic organisms, as all results exceeded the limits set by the guidelines of the European Medicines Agency., i.e., the PEC ranged between 0.37 and 99.39 μg/L. The results of individual ERA showed the following trend: (i) 56.41% of the results of acute toxicity indicated high toxicity for the three trophic levels; 33.33% of the results indicated low risk for one of the trophic levels, and 10.26% indicated moderate toxicity, and (ii) in terms of chronic toxicity, 33.33% of the results indicated moderate risks, 35.90% indicated low or no risk, and 30.77% indicated high risks. Regarding the results of the mixture of ARVs, the ERA showed a high acute and/or chronic risk for all five classes tested, i.e., (i) nucleoside/nucleotide reverse transcriptase inhibitors; ii) non-nucleoside reverse transcriptase inhibitors; iii) protease inhibitors; (iv) integrase strand transfer inhibitors; and (v) chemokine receptor antagonists. Ultimately, the final ranking of the OPBT approach was etravirine (the highest-priority ARV in seawater from Guarujá), followed by: nevirapine > efavirenz > ritonavir > lopinavir > maraviroc > atazanavir > darunavir > abacavir > dolutegravir > zidovudine > tenofovir > lamivudine.