Respiratory Symptoms and Pulmonary Function Among Participants in the MACS/WIHS Combined Cohort Study Using Protease Inhibitors: A Cross-Sectional Study Öffentlichkeit

Terry, Charles (Spring 2021)

Permanent URL: https://etd.library.emory.edu/concern/etds/j96021876?locale=de
Published

Abstract

Objective: People living with human immunodeficiency virus (PLWH) have higher prevalence of cough, dyspnea, and wheezing than HIV-negative populations. While the mechanisms are unknown, antiretroviral therapy (ART) has been associated with worsened airflow limitation. We sought to estimate the prevalence of respiratory symptoms among PLWH and their association with protease inhibitor (PI) use. 

Design: Retrospective cross-sectional study of Multicenter AIDS Cohort Study (MACS) visits from 04/01/2017 to 03/30/2018 and the Women’s Interagency Health Study (WIHS) visits from 10/31/2017 to 09/30/2019.  

Methods: Participants completed the St. George’s Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea scale, and pulmonary function testing. Demographic, clinical, laboratory, and pulmonary function data from each visit were compared among PLWH using PIs, PLWH not using PIs, and HIV-negative groups. Logistic regression was used to estimate the association between PI use and the higher scores of SGRQ (defined as SGRQ>10) and mMRC scores after adjusting for potential confounders.

Results: In the MACS and WIHS cohorts respectively, 77/177 (45.3%) and 117/239 (49.0%) PLWH using PIs had SGRQ scores ≥ 10 while 171/501 (34.7%) and 508/956 (52.8%) of PLWH not using PIs and 162/549 (29.9%) and 266/493 (53.6%) of people living without HIV had SGRQ scores ≥ 10 (p=0.001 and p=0.4218). Adjusted models found an association between PI use and SGRQ score ≥ 10 [OR 1.91 (95% CI 1.29-2.82), ref: HIV-negative and OR 1.50 (95% CI 1.01-2.22) ref: PLWH not using PIs] in the MACS cohort but not the WIHS cohort [OR 0.95 (95% CI 0.68-1.34), ref: HIV-negative and OR 0.84 (95% CI 0.62-1.16) ref: PLWH not using PIs]. Similar associations were found with mMRC scores and PI use [OR 1.79 (95% CI 1.21-2.64), ref: HIV-negative and OR 1.53 (95% CI 1.04-2.25), ref: PLWH not using PIs] but not the WIHS cohort [OR 0.94 (95% CI 0.70-1.27), ref: HIV- negative and OR 0.85 (95% CI 0.65-1.12), ref: PLWH not using PIs].  

Conclusions: PI use is associated with severe respiratory symptoms and an increased prevalence of pulmonary disease among men; however, this finding could not be replicated in the WIHS cohort, suggesting a sex-specific effect modification or unmeasured confounding.

Table of Contents

A. Introduction………………………………………………………………………….....1

B. Background…………………………………………………………………………….3

C. Methods……………………………………………………………………………...…8

D. Results………………………………………………………………………………...15

E. Discussion/Conclusion………………………………………………………………..18

F. References……………………………………………………………………….….....24

G. Tables/Graphs/Charts…………………………………………………………….…...30

Figure 1. Study Cohort Diagrams…………………………………………………….….30

Figure 2. Casual Diagram……………………………………………….……………….31

Table 1. Description of MACS study population, overall, and by HIV serostatus/PI use……………………………………………………………………………….……….32

Table 2. HIV-Specific characteristics among HIV positive MACS participants, overall, and by PI use…………………………………………………………………….……….37

Table 3. Respiratory Symptoms and Pulmonary Function Among MACS Participants, Overall and by HIV serostatus/PI use…..…………………………………………….….39

Figure 3. Logistic Regression Modelling Equations for SGRQ and mMRC Data….…...41

Table 4. MACS Unadjusted mMRC Ordinal Logistic Model Odds Ratio Estimates [HIV-Negative As a Referent Group]……………………………………………………….….42

Table 5. MACS Unadjusted mMRC Ordinal Logistic Model Odds Ratio Estimates [HIV-Positive Not Using PIs As a Referent Group]……………………………………...……43

Table 6. MACS Adjusted mMRC Ordinal Logistic Model Odds Ratio Estimates...…....44

Table 7. MACS Unadjusted SGRQ Logistic Models Odds Ratio Estimates [HIV-Negative As a Referent Group]…………………………………………………………..46

Table 8. MACS Unadjusted SGRQ Logistic Models Odds Ratio Estimates [HIV-Positive Not Using PIs As a Referent Group]………………………………………………...…..47

Table 9. MACS Adjusted SGRQ Logistic Model Odds Ratio Estimates………...…...…48

Table 10. Description of WIHS Population, Overall, and by HIV Serostatus/PI Use.......50

Table 11. HIV-Specific Characteristics Among HIV-Positive WIHS Participants, Overall, and By PI Use………………………………………………………………………..…..55

Table 12. Respiratory Symptoms and Pulmonary Function Among WIHS Participants, Overall and by HIV serostatus/PI use……………………………………………...…….58

Table 13. WIHS Unadjusted mMRC Ordinal Logistic Model Odds Ratio Estimates [HIV-Negative As a Referent Group]…………………………………………………..........…61

Table 14. WIHS Unadjusted mMRC Ordinal Logistic Model Odds Ratio Estimates [HIV-Positive Not Using PIs As a Referent Group]………………………………………...…62

Table 15. WIHS Adjusted mMRC Ordinal Logistic Model Odds Ratio Estimates .....…63

Table 16. WIHS Unadjusted SGRQ Logistic Models Odds Ratio Estimates [HIV-Negative As a Referent Group]……………………………………………………..........65

Table 17. WIHS Unadjusted SGRQ Logistic Models Odds Ratio Estimates [HIV-Positive Not Using PIs As a Referent Group]…………………………………………………….66

Table 18. WIHS Adjusted Logistic SGRQ Score Models……………………………….67

Figure 4. Protease Inhibitors Used in the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS)……………………………………................69

Figure 5. Total St. George’s Respiratory Questionnaire Scores Among Multicenter AIDS Cohort Study (MACS) Groups……………………………………………..……………70

Figure 6. Total St. George’s Respiratory Questionnaire Scores Among Women’s Interagency HIV Study (WIHS) Groups…………………………………………………71

Table 19. Dichotomized SGRQ Scores ≥ 10 and < 10 In Each Cohort…………….……72

Figure 7. mMRC Dyspnea Scale Scores in the MACS and WIHS Cohorts……………..73

Figure 8.MACS Multivariable Ordinal and Binary mMRC and SGRQ Models………...74

Figure 9. WIHS Multivariable Ordinal and Binary mMRC and SGRQ Models………...75

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