Open AccessRoutine data underestimates the incidence of first-line antiretroviral drug discontinuations due to adverse drug reactions: Observational study in two South African cohorts
Author(s) -
Reneé De Waal,
Karen Cohen,
Andrew Boulle,
Matthew P. Fox,
Gary Maartens,
Ehimario U. Igumbor,
MaryAnn Davies
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0203530
Subject(s) - efavirenz , medicine , stavudine , discontinuation , incidence (geometry) , cumulative incidence , pharmacovigilance , regimen , observational study , adverse effect , cohort , viral load , antiretroviral therapy , human immunodeficiency virus (hiv) , family medicine , physics , optics
Estimating the incidence of antiretroviral discontinuations due to adverse drug reactions (ADRs) is important to inform antiretroviral treatment (ART) regimen recommendations, and to guide prescribing and monitoring policies. Routinely collected clinical data is a useful source of pharmacovigilance data. We estimated the incidences of first-line antiretroviral discontinuations due to ADRs using routine clinical data, and compared them with incidences estimated using data enhanced by folder review, in two South African cohorts. Methods We included patients 16 years and older on first-line ART. We selected a stratified random sample of 25% for checking of ART prescription data and reasons for antiretroviral discontinuations retrospectively, including folders reviews where required (enhanced-data sample). We estimated the incidence of antiretroviral discontinuations using Kaplan-Meier and competing risk analyses. Results In 15396 patients, 40% had a first-line antiretroviral discontinuation by three years on ART. We could determine the reason for 65% of discontinuations using routine data only, and 84% of discontinuations, in the enhanced-data sample of 3837 patients. ADR was the most common reason for discontinuations. In the enhanced-data sample, the cumulative incidence of discontinuations due to ADRs by three years was 30.4% (95% CI: 24.4–36.6) for stavudine; 2.0% (95% CI: 1.5–2.6) for tenofovir, and 1.3% (95% CI: 0.8–2.1) for efavirenz. Using routine data only, the cumulative incidences of discontinuations due to ADRs by three years for stavudine, tenofovir, and efavirenz respectively were 23.9% (95% CI: 20.3–27.7), 1.2% (95% CI: 0.9–1.4) and 0.5% (95% CI: 0.3–0.7). Conclusions Although the relative rankings were similar using routine or enhanced data, lack of checking for missing reasons for discontinuation resulted in underestimates of the incidence of antiretroviral discontinuations due to ADRs. Systems to improve data collection of reasons for regimen changes prospectively would increase the capacity of routine data to answer pharmacovigilance questions.