ritonavir and Jaundice

The UGT1A1*28 variant has been associated with hyperbilirubinemia and atazanavir discontinuation. Protocol A5202 randomly assigned human immunodeficiency virus type 1 (HIV-1)-infected patients to receive atazanavir/ritonavir (atazanavir/r) or efavirenz, with tenofovir/emtricitabine or abacavir/lamivudine. A total of 646 atazanavir/r recipients were evaluable for UGT1A1. Homozygosity for *28/*28 was present in 8% of whites, 24% of blacks, and 18% of Hispanics and was associated with increased bilirubin concentrations. There was an association between *28/*28 and increased atazanavir/r discontinuation among Hispanic participants (P = .005) but not among white or black participants (P = .79 and P = .46, respectively). The positive predictive value of 28*/28* for atazanavir/r discontinuation among Hispanic participants was only 32% (95% confidence interval, 16%-52%).

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Bilirubin; Genetic Variation; Genotype; Glucuronosyltransferase; HIV Infections; HIV-1; Humans; Jaundice; Oligopeptides; Pyridines; Ritonavir

Topics: Antiviral Agents; COVID-19 Drug Treatment; Humans; Jaundice; Liver; Lopinavir; Ritonavir; SARS-CoV-2

We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus.. This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group.. Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%).. Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.

Topics: Aged; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Intensive Care Units; Jaundice; Lopinavir; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prospective Studies; Retrospective Studies; Ritonavir; SARS-CoV-2; Severity of Illness Index; Standard of Care

On the basis of a single clinical trial in first-line treatment, the atazanavir and ritonavir combination appears to be no more effective than the fixed-dose combination of lopinavir and ritonavir. The adverse effect profiles were slightly different, but atazanavir carries a troubling risk of torsades de pointes.

Topics: Anti-HIV Agents; Anti-Retroviral Agents; Atazanavir Sulfate; Drug Approval; Drug Therapy, Combination; Europe; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Jaundice; Lopinavir; Oligopeptides; Pyridines; Pyrimidinones; Randomized Controlled Trials as Topic; Ritonavir; Torsades de Pointes; Viral Load

Topics: Adult; Drug Interactions; Drug Therapy, Combination; Fusidic Acid; HIV Infections; HIV Protease Inhibitors; Humans; Jaundice; Liver; Liver Function Tests; Male; Ritonavir; Saquinavir