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Smoking and Accelerated Lung Function Decline in HIV-Positive Individuals

A Secondary Analysis of the START Pulmonary Substudy

MacDonald, David M. MD*; Melzer, Anne C. MD, MS*,†; Collins, Gary MS; Avihingsanon, Anchalee MD, PhD; Crothers, Kristina MD§; Ingraham, Nicholas E. MD*; Mugerwa, Henry MD; Ristola, Matti MD; Shuter, Jonathan MD#; Kunisaki, Ken M. MD, MS*,† for the INSIGHT START Pulmonary Substudy Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: November 1, 2018 - Volume 79 - Issue 3 - p e85–e92
doi: 10.1097/QAI.0000000000001797
Clinical Science

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability globally. Both cigarette smoking and HIV have been identified as independent risk factors for COPD. We used data from the strategic timing of antiretroviral treatment (START) Pulmonary Substudy to quantify the impact of smoking on rate of lung function decline in HIV.

Methods: We included START Pulmonary Substudy participants who contributed at least 2 good quality spirometry measures during the study. Slope of forced expiratory volume in 1 second (FEV1) was estimated using a repeated-measures model adjusted for the treatment group (immediate vs deferred treatment arm of START), age, sex, race, baseline COPD, and region.

Results: Of 1026 START Pulmonary Substudy participants, 915 (89%) were included in this analysis. Median follow-up time was 3.9 years. Smokers and nonsmokers were similar in baseline age (median 36 years), but smokers were more likely to be white, male, and from Europe/Israel/Australia. Smokers had faster average FEV1 decline compared with nonsmokers [−38.3 mL/yr vs −25.1 mL/yr; difference of −13.2 mL/yr (95% confidence interval: −23.6 to −2.7); P = 0.013], were more likely to meet criteria for rapid FEV1 decline [7.2%–11.7% more likely (P = 0.09–P = 0.002), depending on the definition of rapid decline], and had borderline, but not statistically significant, higher incident COPD during follow-up (9.7% vs 5.8%, P = 0.06).

Conclusions: Compared to nonsmokers, HIV-positive smokers experience faster decline in lung function. These results underscore the need for a better understanding of how to best support smoking cessation among HIV-positive populations.

*Minneapolis VA Health Care System, Minneapolis, MN;

University of Minnesota, Minneapolis, MN;

HIV-NAT, Thai Red Cross AIDS Research Centre and Tuberculosis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;

§University of Washington, Seattle, WA;

Joint Clinical Research Centre, Kampala, Uganda;

Helsinki University Hospital, Helsinki, Finland; and

#Montefiore Medical Center, New York, NY.

Correspondence to: Ken M. Kunisaki, MD, MS, Pulmonary and Sleep Medicine (111N), Minneapolis VA Health Care System, One Veterans Drive, Minneapolis, MN 55417 (e-mail:

Supported by the National Heart Lung and Blood Institute (R01 HL096453); the parent START trial was primarily supported by the National Institute of Allergy and Infectious Diseases Division of AIDS (UM1 AI068641 and UM AI120197) with additional support from the German Ministry of Education and Research, the European AIDS Treatment Network (NEAT), the Australian National Health and Medical Research Council, and the UK Medical Research Council and National Institute for Health Research. The Veterans Health Administration Office of Research and Development also provided protected research time in support of this study. The University of Minnesota served as sponsor of the study. None of the funders nor sponsors had any input regarding the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Study Drugs: Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. St. George's Respiratory Questionnaire for COPD: Permission for use granted to investigators by Dr. Paul Jones (St. George's, University of London, London, United Kingdom).

Presented in part at the Conference on Retroviruses and Opportunistic Infections; March 03, 2018; Boston, MA.

G.C., A.A., H.M., M.R., J.S., and K.M.K. received grant support from the National Institutes of Health (R01 HL096453, UM1 AI068641, and UM AI120197) for conduct of this study. K.M.K. has received consultancy fees from GlaxoSmithKline. The remaining authors have no funding or conflicts of interest to disclose.

Conceived the study: D.M.M. and K.M.K.; designed the study: D.M.M. and K.M.K.; obtained funding: K.M.K.; acquired the data: A.A., H.M., M.R., and J.S.; performed the primary statistical analyses: G.C.; drafted the manuscript: D.M.M.; critically revised the manuscript for important intellectual content and approved the final manuscript: D.M.M., G.C., N.E.I., A.C.M., K.C., A.A., H.M., M.R., J.S., and K.M.K.; take responsibility for the integrity of the data and the accuracy of the data analysis: D.M.M., G.C., and K.M.K.

See the START pulmonary substudy (supplemental appendix section) for a complete listing of START Pulmonary Substudy investigators.22

The views expressed in this article are those of the authors and do not reflect the views of the US Government, the National Institutes of Health, the Department of Veterans Affairs, the funders, the sponsors, or any of the authors' affiliated academic institutions.

Received April 11, 2018

Accepted June 25, 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.