Changes over time in creatinine clearance and comparison of emergent adverse events for HIV-positive adults receiving standard doses (300 mg/day) of lamivudine-containing antiretroviral therapy with baseline creatinine clearance of 30–49 vs ≥50 mL/min

Autoři: Lisa L. Ross aff001;  A. Sarah Walker aff002;  Yu Lou aff003;  Allan R. Tenorio aff004;  Diana M. Gibb aff002;  Julia Double aff005;  Charles Gilks aff006;  Cynthia C. McCoig aff007;  Paula Munderi aff008;  Godfrey Musoro aff009;  Cissy M. Kityo aff010;  Heiner Grosskurth aff008;  James Hakim aff009;  Peter N. Mugyenyi aff010;  Amy Cutrell aff011;  Teodora Perger aff012;  Mark S. Shaefer aff001
Působiště autorů: Medical Affairs, ViiV Healthcare, Research Triangle Park, NC, United States of America aff001;  Medical Research Council Clinical Trials Unit, University College, London, United Kingdom aff002;  Statistics, PAREXEL International, Durham, NC, United States of America aff003;  Physicians Group, ViiV Healthcare, Research Triangle Park, NC, United States of America aff004;  Safety and Medical Governance, GlaxoSmithKline, Stockley Park, United Kingdom aff005;  School of Population Health, University of Queensland, Brisbane, Australia aff006;  Physicians Group, ViiV Healthcare, Tres Cantos, Spain aff007;  HIV Care Research Programme, MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda aff008;  Department of Medicine, University of Zimbabwe, Harare, Zimbabwe aff009;  HIV Clinical Trials Unit, Joint Clinical Research Centre, Kampala, Uganda aff010;  Healthcare Statistics, ViiV Healthcare, Research Triangle Park, NC, United States of America aff011;  Safety and Pharmacovigilance, ViiV Healthcare, London, United Kingdom aff012
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
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 ≥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≥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 (<7 mL/min) were observed for participants who entered the trial with CLcr ≥50 mL/min. Substantial increases (> 150 cells/ mm3) 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 ≥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 ≥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.

Klíčová slova:

Adverse events – Creatinine – Hematology – Renal system – Toxicity – Zimbabwe


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2019 Číslo 11