Objective: Few data describe antiretroviral treatment (ART)-related adverse events when treatment is initiated at CD4+ cell counts more than 350 cells/μl. We compared rates of laboratory-defined adverse events (LDAEs) according to CD4+ cell count at ART initiation.
Design: Analysis of on-going cohort study.
Methods: ART-naive persons initiating ART from 2000 to 2010 were included. Chi-square, analysis of variance (ANOVA) and Kruskal–Wallis tests compared characteristics among those starting ART with a CD4+ cell count of 350 or less, 351–499 and at least 500 cells/μl. Time-updated Poisson regression compared rates of LDAE in the three CD4+ cell strata. Cox proportional hazard models compared risk of ART discontinuation.
Results: Nine thousand, four hundred and six individuals were included: median age 37 years, 61% white, 80% men, median viral load 4.8 log copies/ml. Four hundred and forty-seven (4.9%) and 1099 (11.7%) started ART with a CD4+ cell count at least 500 and 351–499 cells/μl, respectively. One thousand, two hundred and eighty-three (13.6%) patients experienced at least one LDAE. The rate of LDAE did not differ between those starting ART with a CD4+ cell count 351–499 and less than 350 cells/μl [relative rate 0.90, 95% confidence interval (CI) 0.74–1.09)], but an increased risk of ART discontinuation was observed (hazard ratio 1.58, 95% CI 1.10–2.27). Those starting ART at CD4+ cell count at least 500 cells/μl had an increased rate of LDAE (relative rate 1.44, 95% CI 1.13–1.82) but were not more likely to discontinue ART (hazard ratio 1.15, 95% CI 0.64–2.09).
Conclusion: This study demonstrates the need to consider ART-related toxicities when initiating therapy at CD4+ cell counts at least 500 cells/μl. Whilst evidence from randomized controlled trials is awaited, the timing of ART initiation in terms of benefits and risks of ART remains an important question.
aResearch Department of Infection and Population Health, UCL
bImperial College London Department of Medicine, London
cThe Lothian University Hospitals NHS Trust, Edinburgh
dSt George's Healthcare NHS Trust, London
eBrighton and Sussex University Hospitals NHS Trust, Brighton
fKings College Hospital NHS Foundation Trust and King's College London
gChelsea and Westminster NHS Foundation Trust, London
hNorth Bristol NHS Trust, Bristol
iRoyal Free Hampstead NHS Trust, London
jSouth Tees Hospital NHS Foundation Trust, Middlesbrough
kMortimer Market Centre, University College Medical School, London, UK.
Correspondence to Miss Sophie Jose, Research Department of Infection and Population Health, UCL, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. E-mail: email@example.com
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc-nd/3.0.
Received November 8, 2013
Accepted January 31, 2014