Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses

• Published in: PloS one Vol. 14; no. 11; p. e0225199
• Main Authors: Ross, Lisa L, Walker, A. Sarah, Lou, Yu, Tenorio, Allan R, Gibb, Diana M, Double, Julia, Gilks, Charles, McCoig, Cynthia C, Munderi, Paula, Musoro, Godfrey, Kityo, Cissy M, Grosskurth, Heiner, Hakim, James, Mugyenyi, Peter N, Cutrell, Amy, Perger, Teodora, Shaefer, Mark S
• Format: Journal Article
• Language: English
• Published: Public Library of Science 14-11-2019
• Subjects: Adults; Analysis; Antiretroviral agents; Bilirubin; Biological products industry; Clinical trials; Dosage and administration; Enzymes; Highly active antiretroviral therapy; HIV; HIV patients; Lamivudine; Liver; Toxicity; United States; Africa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0225199

A retrospective analysis of the randomized controlled DART (Development of AntiRetroviral Therapy in Africa; ISRCTN13968779) trial in HIV-1-positive adults initiating antiretroviral therapy with co-formulated zidovudine/lamivudine plus either tenofovir, abacavir, or nevirapine was conducted to evaluate the safety of initiating standard lamivudine dosing in patients with impaired creatinine clearance (CLcr). Safety data collected through 96 weeks were analyzed after stratification by baseline CLcr (estimated using Cockcroft-Gault) of 30-49 mL/min (n = 168) versus [greater than or equal to]50 mL/min (n = 3,132) and treatment regimen. The Grade 3-4 adverse events (AEs) and serious AEs (for hematological, hepatic and gastrointestinal events), maximal toxicities for liver enzymes, serum creatinine and bilirubin and maximum treatment-emergent hematology toxicities were comparable for groups with baseline CLcr 30-49 versus CLcr[greater than or equal to]50 mL/min. No new risks or trends were identified from this dataset. Substantial and similar increases in the mean creatinine clearance (>25 mL/min) were observed from baseline though Week 96 among participants who entered the trial with CLcr 30-49 mL/min, while no increase or smaller median changes in creatinine clearance ( 150 cells/ mm.sup.3) in mean CD4+ cells counts from baseline to Week 96 were also observed for participants who entered the trial with CLcr 30-49 mL/min and those with baseline CLcr [greater than or equal to]50 mL/min. Though these results are descriptive, they suggest that HIV-positive patients with CLcr of 30-49 mL/min would have similar AE risks in comparison to patients with CLcr [greater than or equal to]50 mL/min when initiating antiretroviral therapy delivering doses of 300 mg of lamivudine daily through 96 weeks of treatment. Overall improvements in CLcr were observed for patients with baseline CLcr 30-49 mL/min.