TY - JOUR
T1 - Changes in lung function among treated HIV-positive and HIV-negative individuals: analysis of the prospective AGEhIV cohort study
AU - Verboeket, Sebastiaan O.
AU - Boyd, Anders
AU - Wit, Ferdinand W.
AU - Verheij, Eveline
AU - Schim van der Loeff, Maarten F.
AU - Kootstra, Neeltje
AU - van der Valk, Marc
AU - van Steenwijk, Reindert P.
AU - Drummond, M. Bradley
AU - AGEhIV Cohort Study
AU - Kirk, Gregory D.
AU - Reiss, Peter
N1 - Funding Information: FWW has served on scientific advisory boards for ViiV Healthcare and Gilead sciences. MFSvdL has received independent scientific grant support from Sanofi Pasteur, MSD Janssen Infectious Diseases and Vaccines, and Merck; has served on the advisory board of GlaxoSmithKline; and has received non-financial support from Stichting Pathologie Onderzoek en Ontwikkeling. MvdV through his institution has received independent scientific grant support and consultancy fees from AbbVie, Gilead Sciences, Johnson & Johnson, MSD, and ViiV Healthcare, for which honoraria were all paid to his institution. MBD has participated in advisory consulting or received research support from the following companies outside of this work: AstraZeneca, Boehringer-Ingelheim, Enterprise Therapeutics, GlaxoSmithKline, Midmark, Parion, Teva, and Theravance Biopharma/Mylan; he has received grant support from the National Institutes of Health and the US Department of Defense outside of this work. GDK was supported by a Fulbright Global Scholar award (US Department of State) and by the National Institute of Allergy and Infectious Diseases (grant number K24-AI118591). PR through his institution has received independent scientific grant support from Gilead Sciences, ViiV Healthcare, Merck, and Janssen Pharmaceuticals, and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, Merck, and Teva pharmaceutical industries, for which his institution has received remuneration. SOV, AB, EV, NK, and RPvS declare no competing interests. Funding Information: This work was supported by The Netherlands Organization for Health Research and Development (ZonMW; grant number 300020007) and AIDS Fonds (grant number 2009063). Additional unrestricted scientific grants were received from Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, and Merck Publisher Copyright: © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Background: The AGE hIV cohort study is a prospective cohort study evaluating the occurrence of age-related comorbidities in people living with and without HIV. We previously reported a lower forced vital capacity (FVC) in HIV-positive compared with HIV-negative participants in those without heavy smoking exposure at time of enrolment in the AGE hIV cohort study. In this study we evaluate longitudinal changes in spirometry indices in the same AGE hIV cohort accounting for smoking behaviour and other risk factors. Methods: We obtained pre-bronchodilator spirometry measurements in AGE hIV cohort participants during biennial visits over a median of 5·9 years (IQR 5·7–6·0). Adjusted declines in forced expiratory volume in 1 s (FEV 1), FVC, and FEV 1/FVC ratio were modelled using linear mixed-effects models and compared by HIV status and smoking status. To evaluate whether changes in spirometry measurements could be driven by increased levels of chronic inflammation, we assessed associations between rates of FEV 1 and FVC decline and CD4 and CD8 T-cell counts, and plasma concentrations of C-reactive protein (CRP), interleukin 6, soluble CD14, soluble CD163, and intestinal fatty-acid-binding protein in separate models. The study is registered at ClinicalTrials.gov, NCT01466582. Findings: 500 HIV-positive and 481 HIV-negative participants were included with spirometry data from Oct 29, 2010, to Aug 14, 2018. HIV-positive participants were virally suppressed (<40 copies per mL) during 1627 (95%) study visits, and 159 (32%) HIV-positive and 183 (38%) HIV-negative participants had never smoked. Adjusted declines in FEV 1 were 10·0 mL per year faster in HIV-positive non-smokers (95% CI 4·2 to 15·7, p=0·00066) compared with HIV-negative non-smokers, and 11·1 mL per year faster in HIV-positive smokers (95% CI 0·7 to 21·4, p=0·036) compared with HIV-negative smokers. In comparison, smoking was associated with a 16·4 mL per year steeper decline in FEV 1 among HIV-positive participants (95% CI 8·0 to 24·7, p=0·00012), and 15·3 mL per year steeper decline among HIV-negative participants (95% CI 6·7–24·0, p=0·00052) compared with not smoking. Adjusted yearly declines in FEV 1 and FVC, but not FEV 1/FVC, were significantly greater in HIV-positive than HIV-negative participants overall (additional decline in HIV-positive participants, FEV 1 10·5 mL per year [95% CI 4·7 to 16·3], p=0·00040; FVC 11·5 mL per year [2·8 to 20·3], p=0·0096; FEV 1/FVC 0·07% per year [–0·05 to 0·19], p=0·26), with a similar observation for never-smokers (FEV 1 6·0 mL per year [–1·8 to 13·7], p=0·13; FVC 9·1 mL per year [–3·0 to 21·1], p=0·14; FEV 1/FVC ratio 0·00% per year [–0·18 to −0·18], p=0·97). Higher CRP concentrations during follow-up were associated with accelerated declines in FEV 1 and FVC among HIV-positive participants but not among HIV-negative participants. Interpretation: Treated HIV infection was associated with faster declines in both FEV 1 and FVC, but not in the FEV 1/FVC ratio. These changes were independent of smoking and might have been driven by ongoing interstitial or small airway damage, potentially related to increased inflammation. Funding: ZonMW, Aidsfonds, Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, Merck.
AB - Background: The AGE hIV cohort study is a prospective cohort study evaluating the occurrence of age-related comorbidities in people living with and without HIV. We previously reported a lower forced vital capacity (FVC) in HIV-positive compared with HIV-negative participants in those without heavy smoking exposure at time of enrolment in the AGE hIV cohort study. In this study we evaluate longitudinal changes in spirometry indices in the same AGE hIV cohort accounting for smoking behaviour and other risk factors. Methods: We obtained pre-bronchodilator spirometry measurements in AGE hIV cohort participants during biennial visits over a median of 5·9 years (IQR 5·7–6·0). Adjusted declines in forced expiratory volume in 1 s (FEV 1), FVC, and FEV 1/FVC ratio were modelled using linear mixed-effects models and compared by HIV status and smoking status. To evaluate whether changes in spirometry measurements could be driven by increased levels of chronic inflammation, we assessed associations between rates of FEV 1 and FVC decline and CD4 and CD8 T-cell counts, and plasma concentrations of C-reactive protein (CRP), interleukin 6, soluble CD14, soluble CD163, and intestinal fatty-acid-binding protein in separate models. The study is registered at ClinicalTrials.gov, NCT01466582. Findings: 500 HIV-positive and 481 HIV-negative participants were included with spirometry data from Oct 29, 2010, to Aug 14, 2018. HIV-positive participants were virally suppressed (<40 copies per mL) during 1627 (95%) study visits, and 159 (32%) HIV-positive and 183 (38%) HIV-negative participants had never smoked. Adjusted declines in FEV 1 were 10·0 mL per year faster in HIV-positive non-smokers (95% CI 4·2 to 15·7, p=0·00066) compared with HIV-negative non-smokers, and 11·1 mL per year faster in HIV-positive smokers (95% CI 0·7 to 21·4, p=0·036) compared with HIV-negative smokers. In comparison, smoking was associated with a 16·4 mL per year steeper decline in FEV 1 among HIV-positive participants (95% CI 8·0 to 24·7, p=0·00012), and 15·3 mL per year steeper decline among HIV-negative participants (95% CI 6·7–24·0, p=0·00052) compared with not smoking. Adjusted yearly declines in FEV 1 and FVC, but not FEV 1/FVC, were significantly greater in HIV-positive than HIV-negative participants overall (additional decline in HIV-positive participants, FEV 1 10·5 mL per year [95% CI 4·7 to 16·3], p=0·00040; FVC 11·5 mL per year [2·8 to 20·3], p=0·0096; FEV 1/FVC 0·07% per year [–0·05 to 0·19], p=0·26), with a similar observation for never-smokers (FEV 1 6·0 mL per year [–1·8 to 13·7], p=0·13; FVC 9·1 mL per year [–3·0 to 21·1], p=0·14; FEV 1/FVC ratio 0·00% per year [–0·18 to −0·18], p=0·97). Higher CRP concentrations during follow-up were associated with accelerated declines in FEV 1 and FVC among HIV-positive participants but not among HIV-negative participants. Interpretation: Treated HIV infection was associated with faster declines in both FEV 1 and FVC, but not in the FEV 1/FVC ratio. These changes were independent of smoking and might have been driven by ongoing interstitial or small airway damage, potentially related to increased inflammation. Funding: ZonMW, Aidsfonds, Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, Merck.
UR - http://www.scopus.com/inward/record.url?scp=85103382455&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S2666-7568(21)00033-7
DO - https://doi.org/10.1016/S2666-7568(21)00033-7
M3 - Article
SN - 2666-7568
VL - 2
SP - e202-e211
JO - The Lancet Healthy Longevity
JF - The Lancet Healthy Longevity
IS - 4
ER -