Evidence for risk stratification when monitoring for toxicities following initiation of combination antiretroviral therapy

Taiwo, Babafemia; Yanik, Elizabeth L.b; Napravnik, Soniab; Ryscavage, Patrickc; Koletar, Susan L.d; Moore, Richarde; Mathews, W. Christopherf; Crane, Heidi M.g; Mayer, Kennethh; Zinski, Annei; Kahn, James S.j; Eron, Joseph J.b

doi: 10.1097/QAD.0b013e3283601115
Clinical Science

Objective: Laboratory monitoring is recommended during combination antiretroviral therapy (cART), but the pattern of detected abnormalities and optimal monitoring are unknown. We assessed laboratory abnormalities during initial cART in 2000–2010 across the United States.

Design: Observational study in the Centers for AIDS Research Network of Integrated Clinical Systems Cohort.

Methods: Among patients with normal results within a year prior to cART initiation, time to first significant abnormality was assessed by Kaplan–Meier curves stratified by event type, with censoring at first of regimen change, loss to follow-up, or 104 weeks. Incidence rates of first events were estimated using Poisson regression; multivariable analyses identified associated factors. Results were stratified by time (16 weeks) from therapy initiation.

Results: A total of 3470 individuals contributed 3639 person-years. Median age, pre-cART CD4, and follow-up duration were 40 years, 206 cells/μl, and 51 weeks, respectively. Incidence rates for significant abnormalities (per 100 person-years) in the first 16 weeks post-cART initiation were as follows: lipid = 49 [95% confidence interval (CI) 41–58]; hematologic = 44 (40–49); hepatic = 24 (20–27); and renal = 9 (7–11), dropping substantially during weeks 17–104 of cART to lipid = 23 (18–29); hematologic = 5 (4–6); hepatic = 6 (5–8); and renal = 2 (1–3) (all P < 0.05). Among patients receiving initial cART with no prior abnormality (N = 1889), strongest associations for hepatic abnormalities after 16 weeks were hepatitis B and C [hazard ratio = 2.3 (95% CI 1.2–4.5) and hazard ratio = 3.0 (1.9–4.5), respectively]. The strongest association for renal abnormalities was hypertension [hazard ratio = 2.8 (1.4–5.6)].

Conclusion: New abnormalities decreased after week 16 of cART. For abnormalities not present by week 16, subsequent monitoring should be guided by comorbidities.

aNorthwestern University, Chicago, Illinois

bUniversity of North Carolina, Chapel Hill, North Carolina

cUniversity of Maryland, Baltimore, Maryland

dOhio State University, Columbus, Ohio

eJohns Hopkins University, Baltimore, Maryland

fUniversity of California, San Diego, California

gUniversity of Washington, Seattle, Washington

hBeth Israel Deaconess Medical Center, Boston, Massachusetts

iUniversity of Alabama, Birmingham, Alabama

jVeterans Administration Palo Alto Healthcare System, Palo Alto, California, USA.

Correspondence to Babafemi Taiwo, MBBS, Infectious Diseases Division, Northwestern University, 645 N Michigan Avenue, Chicago, IL 60611, USA. Tel: +1 312 695 5085; e-mail: b-taiwo@northwestern.edu

Received 26 November, 2012

Revised 31 January, 2013

Accepted 11 February, 2013

© 2013 Lippincott Williams & Wilkins, Inc.