Determinants of Viremia Copy-Years in People With HIV/AIDS After Initiation of Antiretroviral Therapy

Wright, Stephen T. MAppStat*; Hoy, Jennifer MBBS†,‡; Mulhall, Brian MBBS*,§; O'Connor, Catherine C. DrPH, MM*,‖,¶; Petoumenos, Kathy PhD*; Read, Timothy PhD#; Smith, Don MD**,††; Woolley, Ian MD†,‡‡; Boyd, Mark A. MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000125
Clinical Science
Abstract

Background: Recent studies suggest higher cumulative HIV viremia exposure measured as viremia copy-years (VCY) is associated with increased all-cause mortality. The objectives of this study are (1) report the association between VCY and all-cause mortality and (2) assess associations between common patient characteristics and VCY.

Methods: Analyses were based on patients recruited to the Australian HIV Observational Database (AHOD) who had received ≥24 weeks of antiretroviral therapy (ART). We established VCY after 1, 3, 5, and 10 years of ART by calculating the area under the plasma viral load time series. We used survival methods to determine the association between high VCY and all-cause mortality. We used multivariable mixed-effect models to determine predictors of VCY. We compared a baseline information model with a time-updated model to evaluate discrimination of patients with high VCY.

Results: Of the 3021 AHOD participants who initiated ART, 2073 (69%), 1667 (55%), 1267 (42%), and 638 (21%) were eligible for analysis at 1, 3, 5, and 10 years of ART, respectively. Multivariable-adjusted hazard ratio association between all-cause mortality and high VCY was statistically significant, hazard ratio 1.52 (1.09, 2.13), P = 0.01. Predicting high VCY after 1 year of ART for a time-updated model compared with a baseline information model, the area under the sensitivity/specificity curve was 0.92 vs. 0.84; and at 10 years of ART, area under the sensitivity/specificity curve was 0.87 vs. 0.61, respectively.

Conclusion: A high cumulative measure of viral load after initiating ART is associated with increased risk of all-cause mortality. Identifying patients with high VCY is improved by incorporating time-updated information.

Author Information

*The Kirby Institute, University of New South Wales, Sydney, Australia;

Department of Medicine, Monash University, Melbourne, Australia;

Infectious Diseases Unit, The Alfred Hospital, Melbourne, Australia;

§School of Public Health, University of Sydney, Sydney, Australia;

RPA Sexual Health, Royal Prince Alfred Hospital, Sydney, Australia;

Central Clinical School, University of Sydney, Sydney, Australia;

#Melbourne Sexual Health Center, The Alfred Hospital, Melbourne, Australia;

**The Albion Center, Sydney, Australia;

††School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia; and

‡‡Infectious Diseases, Monash Medical Centre, Melbourne, Australia.

Correspondence to: Stephen T. Wright, MAppStat, The Kirby Institute, University of New South Wales, Sydney NSW 2012 (e-mail: swright@kirby.unsw.edu.au).

The Australian HIV Observational Database is funded as part of the Asia Pacific HIV Observational Database, a program of The Foundation for AIDS Research, amfAR, and is supported in part by a grant from the US National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) (Grant U01-AI069907) and by unconditional grants from Merck Sharp & Dohme, Gilead, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Pfizer, GlaxoSmithKline, and Janssen-Cilag. The Kirby Institute is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, The University of New South Wales. The views expressed in this publication do not necessarily represent the position of the Australian Government.

The authors have no conflicts of interest to disclose.

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Received October 17, 2013

Accepted December 31, 2013

© 2014 by Lippincott Williams & Wilkins