Incidence of and Risk Factors for Adverse Drug Reactions in a Prospective Cohort of HIV-Infected Adults Initiating Protease Inhibitor—Containing Therapy

• Published in: Clinical infectious diseases Vol. 39; no. 2; pp. 248 - 255
• Main Authors: Duval, Xavier, Journot, Valérie, Leport, Catherine, Chêne, Geneviève, Dupon, Michel, Cuzin, Lise, May, Thierry, Morlat, Philippe, Waldner, Anne, Salamon, Roger, Raffi, François
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15-07-2004; University of Chicago Press
• Subjects: Adult; Adverse drug reactions; AIDS; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretrovirals; Antiviral agents; Biological and medical sciences; Colic - chemically induced; Female; Hepatitis C virus; Hepatitis, Viral, Human - complications; Highly active antiretroviral therapy; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV Protease Inhibitors - adverse effects; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Incidence; Indinavir - adverse effects; Infections; Infectious diseases; Kidney Diseases - chemically induced; Male; Medical sciences; Memory interference; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Predisposing factors; Probability; Prospective Studies; Protease inhibitors; Renal Insufficiency - complications; Risk Factors; RNA; Time Factors; Transaminases - blood; Urinary lithiasis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Antiretroviral agent; Toxicity; Hepatic disease; Metalloendopeptidases; Epidemiology; Incidence; Pitrilysin; Microbiological investigation; Adult; Antiviral; Indinavir; Human; Immunopathology; Urinary system disease; Enzyme; Critically ill; Transferases; Enzyme inhibitor; AIDS; Urinary tract disease; Immune deficiency; Urinary stone; Infection; Peptidases; Chemotherapy; Treatment; Viral disease; Transaminases; Renal colic; Risk factor; Lithiasis; Mental disorder; Digestive diseases; Hydrolases; Protease inhibitor
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/422141

Risk factors associated with the occurrence of protease inhibitor (PI)—related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval [CI], 6.8–8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline characteristics, plasma human immunodeficiency virus RNA levels of ⩾5 log10 copies/mL (hazard ratio [HR], 1.5; 95% CI, 1.1–2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1–1.2), creatinine clearance levels of <70 mL/min (HR, 2.1; 95% CI, 1.2–3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8–3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2–2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.