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Chronic obstructive pulmonary disease (COPD)

in a large international cohort of HIV-infected adults with CD4+ >500 cells/mm3

Ken Kunisaki, M.D., M.S.

Co-authors: Dennis Niewoehner, Gary Collins, Daniel Nixon, Ellen Tedaldi,

Christopher Akolo, Cissy Kityo, Hartwig Klinker, Alberto La Rosa, John Connett, and

the INSIGHT START Study Team

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Conflicts of Interest

• I have no conflicts of interest to report

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COPD: Chronic Obstructive Pulmonary Disease

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HIV Increases COPD Risk• Main COPD risk factor is

cigarette smoking• HIV is also a COPD risk factor Kuhlman

1989, Gelman 1999, Diaz 2000, Morris 2000, Crothers 2006, Crothers 2011, Drummond 2011, Drummond 2013, Nakamura 2014

• COPD prevalence in PLWH varies from 3%-23% George 2009, Cui 2010, Gingo 2010, Hirani 2011, Kristoffersen 2012, Drummond 2013, Madeddu 2013, Samperiz 2013, Nakamura 2014

• We aimed to assess COPD prevalence in a large, multi-site, multi-national sample of PLWH.

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START Pulmonary Substudy

• Strategic Timing of Antiretroviral Treatment (START) Trial– Infected with HIV-1, naïve to ART– CD4 >500 cells/mm3

– Age ≥18– Not currently pregnant

• Pulmonary Substudy– Age ≥25– No asthma medication use– No contraindications to post-bronchodilator spirometry

• Unstable heart disease, surgery within 6 months, respiratory illness within 6 weeks, allergy to albuterol/salbutamol

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Methods• Post-bronchodilator spirometry

– FEV1

– FVC– FEV1/FVC ratio

FEV1/FVC <5th %tile

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Enrollment

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DemographicsTotal Africa Asia EUR / ISR /

AUSMEX /

S. AmericaUSA

n 1026 328 (32.0%)

103 (10.0%) 313 (30.5%) 191 (18.6%) 91 (8.9%)

Age (years) 36 37 (32, 44) 36 (30, 41) 38 (31, 45) 34 (29, 40) 36 (29, 47)

Female 29.1% 211

(64.3%)27 (26.2%) 26 (8.3%) 26 (13.6%) 9 (9.9%)

Years of HIV dx

1.2 (0.4, 3.5)

1.5 (0.5,

4.8)0.8 (0.2, 3.4) 1.2 (0.5, 3.5) 0.6 (0.3, 2.2) 1.5 (0.4, 4.6)

CD4 cells/mm3

648 (583, 767)

695 (603,

814)618 (561, 728) 634 (581, 738) 632 (574, 718) 674 (582, 773)

Log HIV copies/mL

4.2 (3.5, 4.7)

3.8 (3.0,

4.6)4.5 (3.9, 4.9) 4.3 (3.8, 4.7) 4.4 (3.9, 4.8) 3.9 (3.3, 4.5)

VL ≤ 400 copies/mL 9.5% 62 (19.0%) 6 (5.9%) 9 (2.9%) 9 (4.7%) 11 (12.1%)

Current smoker 28.2% 46 (14.0%) 20 (19.4%) 140 (44.7%) 53 (28.0%) 30 (33.0%)

Former smoker 10.8% 19 (5.8%) 11 (10.7%) 42 (13.4%) 27 (14.3%) 12 (13.2%)

Never smoker 60.9% 263

(80.2%)72 (69.9%) 131 (41.9%) 109 (57.7%) 49 (53.8%)

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Regional DemographicsTotal Africa Asia EUR / ISR /

AUSMEX /

S. AmericaUSA

n 1026 328 103 313 191 91

Age (years) 36 37 36 38 34 36

Female 29.1% 64.3% 26.2% 8.3% 13.6% 9.9%

Years of HIV dx 1.2 1.5 0.8 1.2 0.6 1.5

CD4 cells/mm3 648 695 618 634 632 674

Log HIV copies/mL 4.2 3.8 4.5 4.3 4.4 3.9

VL ≤ 400 copies/mL 9.5% 19.0% 5.9% 2.9% 4.7% 12.1%

Current smoker 28.2% 14.0% 19.4% 44.7% 28.0% 33.0%

Former smoker 10.8% 5.8% 10.7% 13.4% 14.3% 13.2%

Never smoker 60.9% 80.2% 69.9% 41.9% 57.7% 53.8%

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COPD Prevalence

Overall COPD prevalence 6.8% (95% CI: 5.3% - 8.5%)

Total Africa Asia EUR / ISR / AUS

MEX / S.

AMER

USA p-value

n=988 n=322 n=102 n=298 n=181 n=85

FEV1/FVC <LLN 6.8% 7.8% 2.0% 9.1% 3.3% 8.2% p=0.03

COPD Severity, FEV1:

≥80% pred 52.2% 40.0% 100.0% 66.7% 66.7% 14.3%

50%-79% pred 43.3% 60.0% 0.0% 25.9% 33.3% 71.4%

30%-49% pred 4.5% 0.0% 0.0% 7.4% 0.0% 14.3%

<30% pred 0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

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COPD Prevalence – Region

Total Africa Asia EUR / ISR / AUS

MEX / S.

AMER

USA p-value

FEV1/FVC <LLN 6.8% 7.8% 2.0% 9.1% 3.3% 8.2% p=0.03

COPD Severity

--FEV1 ≥80%

pred.52.2% 40.0% 100.0% 66.7% 66.7% 14.3%

--FEV1 50%-79%

pred.43.3% 60.0% 0.0% 25.9% 33.3% 71.4%

--FEV1 30%-49%

pred.4.5% 0.0% 0.0% 7.4% 0.0% 14.3%

--FEV1 <30%

pred.0.0% 0.0% 0.0% 0.0% 0.0% 0.0%

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COPD by Age & Smoking  Total FEV1/FVC <LLN

Overall cohort 988 (100%) 67 (6.8%)

 

Smoking status

Current 27.5% 11.8%

Former 11.1% 2.7%

Never 61.3% 5.3%

p-value - <0.001

 

Age (years) quartile

25 – 30 25.7% 3.9%

31 – 36 25.8% 6.7%

37 – 44 25.3% 7.6%

>44 23.2% 9.2%

p-value - 0.13

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Spirometry Regression Analysis

• Multivariate linear regression

• Lower FEV1/FVC ratio associated with:– Older age (p<0.0001)– Increased smoking pack-years (p<0.0001)– Differed by region (p=0.01)

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Conclusions

• Successfully enrolled 1,026 adult PLWH (CD4>500, naïve to ART) from 80 sites and 20 countries

• COPD: – is not uncommon (6.8%)– appears to relate strongest to smoking and

aging– varies by global region

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Clinical Implications

• Smoking cessation

• COPD as PLWH age

• Need to familiarize PLWH providers with tools for COPD screening, diagnosis, management

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Future Directions

• Prospective data– Kristoffersen 2012: n=63 (Denmark); 9.5%

COPD prevalence at baseline; 19.0% at 4.4 year follow-up.

• ART effect on lung function decline– Conflicting data on ART as COPD risk factor– Randomized allocation will address this

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Acknowledgements

• 80 sites around the world• University of Minnesota (USA)

– Gary Collins, Mollie Roediger-Poelhman, Carol Miller, John Connett, Dennis Niewoehner

• The Kirby Institute (Australia)– Cate Carey, Simone Jacoby, Vida

Shahamat, Megan Clewett

• Copenhagen HIV Programme (Denmark)– Bitten Aagaard, Mary Pearson, Per

Jansson, Daniella Gey

Thank you to each of the 1,026 substudy participants

• MRC Clinical Trials Unit (UK)– Nafisah Braimah, Fleur Hudson,

Michelle Gabriel, Nicki Doyle

• CPCRA (USA)– Betsy Finley, Adriana Sanchez

• Ellen Tedaldi (Temple Univ, USA)• Daniel Nixon (VCU, USA)• Jorgen Vestbo (Manchester Univ, UK)

Study funded byR01 HL096453

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Multivariate Linear Regression