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Associations between baseline biomarkers and lung function in HIV-positive individuals.

ABSTRACT: OBJECTIVE:The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons. DESIGN:Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test. METHODS:We performed linear regression of baseline forced expiratory volume in 1?s (FEV1), forced vital capacity (FVC) and FEV1/FVC and their longitudinal slopes on log2-transformed baseline biomarkers with adjustment for age, sex, race, region, smoking status, baseline CD4+ T-cell counts and baseline HIV-RNA. Biomarkers included D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-27, serum amyloid A, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, albumin and total bilirubin. RESULTS:Among 903 included participants, baseline median age was 36 years, CD4+ cell count was 647?cells/?l, and 28.5% were current smokers. In adjusted analyses, elevated markers of systemic inflammation (hsCRP, IL-6 and serum amyloid A) were associated with lower baseline FEV1 and FVC. Elevated D-dimer and IL-6 were associated with worse airflow obstruction (lower FEV1/FVC). Despite these cross-sectional associations at baseline, no associations were found between baseline biomarkers and subsequent longitudinal lung function decline over a median follow-up time of 3.9 years (3293 spirometry-years of follow-up). CONCLUSION:Commonly available biomarkers, in particular markers of systemic inflammation, are associated with worse cross-sectional lung function, but do not associate with subsequent lung function decline among HIV-positive persons with early HIV infection and baseline CD4 T-cell counts more than 500?cells/?l.

SUBMITTER: MacDonald DM

PROVIDER: S-EPMC6399058 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Associations between baseline biomarkers and lung function in HIV-positive individuals.

MacDonald David M DM Zanotto Alexander D AD Collins Gary G Baker Jason V JV Czarnecki Marcin M Loiza Eliana E Nixon Daniel E DE Papastamopoulos Vasileios V Wendt Chris H CH Wood Robin R Kunisaki Ken M KM

AIDS (London, England) 20190301 4

<h4>Objective</h4>The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons.<h4>Design</h4>Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test.<h4>Methods</h4>We performed linear ...[more]

PMID: 30601153

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Project description:BackgroundSeveral antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown.MethodsD:A:D study participants with an estimated glomerular filtration rate (eGFR) of ? 90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ? 70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ? 60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD]) or until the last eGFR measurement during follow-up. An eGFR was considered confirmed if it was detected at 2 consecutive measurements ? 3 months apart. Predictors and eGFR-related ARV discontinuations were identified using Poisson regression.ResultsOf 22 603 persons, 468 (2.1%) experienced a confirmed eGFR of ? 70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up [95% confidence interval {CI}, 4.35-5.22]) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up [95% CI, 1.10-1.56]) during a median follow-up duration of 4.5 years (interquartile range [IQR], 2.7-6.1 years). A current eGFR of 60-70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio [aIRR], 1.72 [95% CI, 1.38-2.14]) but not other ARVs compared with a current eGFR of ? 90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year [95% CI, 1.12-1.25]) and ritonavir-boosted atazanavir use (aIRR, 1.19/year [95% CI, 1.09-1.32]) were independent predictors of a confirmed eGFR of ? 70 but were not significant predictors of CKD whereas ritonavir-boosted lopinavir use was a significant predictor for both end points (aIRR, 1.11/year [95% CI, 1.05-1.17] and 1.22/year [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs.ConclusionsTenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.

Project description:RationaleHuman immunodeficiency virus (HIV) infection is associated with pulmonary disease and worse lung function, but the relationship of lung function with survival in HIV is unknown.ObjectivesTo determine whether lung function is associated with all-cause mortality in HIV-infected individuals.MethodsHIV-infected participants from cohorts in three locations underwent pre- and post-bronchodilator spirometry and determination of single-breath diffusing capacity of the lung for carbon monoxide (DlCO) in 2008-2009, computed tomographic (CT) scanning of the chest for quantitative emphysema and airway measures, and echocardiography for estimated left ventricular systolic and diastolic function and tricuspid regurgitant velocity. Bivariate analysis and multivariable Cox proportional hazards models were used to determine whether decreased lung function was independently associated with increased all-cause mortality. Models were adjusted for covariates including age, sex, body mass index, smoking status, self-reported hepatitis C status, HIV viral levels, CD4+ T-cell counts, hemoglobin, antiretroviral therapy, and illicit drug use.ResultsOverall, 396 HIV-infected participants underwent pulmonary function testing. Thirty-two participants (8%) died during a median follow-up period of 69 months. A post-bronchodilator FEV1-to-FVC ratio less than 0.7 (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.10-5.58) and a DlCO less than 60% (HR, 2.28; 95% CI, 1.08-4.82) were independently associated with worse mortality. Also, hepatitis C (HR, 2.68; 95% CI, 1.22-5.89) and baseline plasma HIV RNA level (HR per ln RNA copies/ml, 1.50; 95% CI, 1.22-1.86) were associated with mortality in HIV-infected participants. The only CT or echocardiographic measure associated with greater mortality in univariate analysis was greater wall thickness of medium-sized airways (HR for wall area percent, 1.08; 95% CI, 1.00-1.18; P = 0.051), but none of the CT or echocardiogram measures were associated with mortality in multivariable analysis.ConclusionsAirflow obstruction and impaired diffusing capacity appear to be associated with all-cause mortality in HIV-infected persons over an average of 6 years of follow-up. These data highlight the importance of lung dysfunction in HIV-infected persons and should be confirmed in larger cohorts and with extended follow-up periods. Clinical trial registered with www.clinicaltrials.gov (NCT00869544, NCT01326572).

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Associations between baseline biomarkers and lung function in HIV-positive individuals.

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Associations between baseline biomarkers and lung function in HIV-positive individuals.

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