1. Lung Diseases in HIV-infected Veterans
Kristina Crothers, MD
Assistant Professor
Division of Pulmonary and Critical Care Medicine
University of Washington, Seattle, WA, USA

2. Lung Disease in HIV Pre-HAART Era
Lung diseases are one of the most frequent complications of HIV infection1,2
Cause of significant morbidity and mortality
Most common3
Outpatient: URI, Bronchitis
Inpatient: Bacterial pneumonia, Pneumocystis pneumonia (PCP), Tuberculosis (TB)
Higher rates of all diseases compared to HIV-
We know from studies conducted prior to HAART that lung diseases occur more commonly in HIV+ patients, and that the most common conditions were infectious. However, increased COPD and lung
1. Murray and Mills, Am Rev Resp Dis 1990; 141:
2. Rosen et al. AJRCCM 1997; 155:67-71.
3. Wallace et al. AJRCCM 1997; 155:72-80.

3. Lung Disease in Aging, HIV-infected Populations
Increasing importance of non-infectious comorbidities on HIV+ patient outcomes1
Increased emphysema, lung cancer, pulmonary hypertension reported in HIV2,3
Greater proportion of respiratory related admissions from COPD, non-AIDS events4
However, the spectrum of illnesses encountered in HIV is changing as patients are living longer on effective ARVs – increasing importance of non-infectious conditions, may be reflected in lung diseases as well
Braithwaite et al. Am J Med 2005; 118:
Diaz et al. Annals of Int Med. 2000;132:
3. Grulich et al. AIDS 1999;13:
4. Grubb et al. AIDS 2006; 20:

4. Consequences of Smoking in HIV
50-60% of HIV+ patients currently smoke
Impact on mortality - contradictory results in pre-HAART era1-3
HAART era (VACS3), current smokers have4
Increased mortality
Decreased HRQL
Increased COPD, bacterial pneumonia
1. Burns et al. J AIDS Hum Retrovirol 1996;13(4):
2. Page-Shafer et al. Ann Epidemiol 1996;6(5):
3. Galai et al. J Acquir Immune Defic Syndr Hum Retrovirol 1997;14(5):451-8.
4. Crothers et al. JGIM 2005; 20:

5. Smoking and HIV: Independent risk factors for COPD
Veterans Aging Cohort 5 Site Study
HIV+ veterans: 50-60% more COPD
AOR* 1.47 (95% CI ) by ICD-9
AOR* 1.58 (95% CI ) by pt-report
Supports independent risk from HIV
* Adjusted for age, race/ethnicity, pack years, IDU, alcohol abuse
Crothers et al. Chest, 2006; 130(5):

6. Ongoing work within VACS The INHALE Study
“INvestigations in HIV Associated Lung Events”
Compare incidence, risk factors and outcomes of lung disease in HIV+ to HIV-
Determine independent risk from HIV
Extent to which lung diseases are related to smoking and concomitant COPD

7. Incidence of Lung Disease in HIV-infected Veterans
VACS Virtual Cohort
33,420 HIV +
3,707 HIV +
Median follow-up:
8 years
through 7/2007
66,840 HIV -
9,890 HIV -
Veterans 1999
Large Health Survey
Self-reported smoking status

8. Unadjusted incidence rate per 1,000 PY (95% CI)

9. Unadjusted incidence per 1,000 PY

10. Age-stratified adjusted incidence rate ratios for pulmonary disease in HIV+ to HIV-
Age < Age ≥50
Disease IRR IRR
TB * 5.4*
Bacterial PNA 5.1* 2.8*
Lung cancer 2.1* 1.7*
Fibrosis 1.6* 1.5*
PAH * 1.6*
COPD 1.2* 1.1*
Asthma
Results similar in models adjusting for smoking *p<0.05

11. Incidence of lung disease in HIV+ Veterans in HAART era
Increased incidence of infectious and non-infectious lung diseases
Substantial burden of non-AIDS defining and chronic conditions
Aging
Smoking
HIV+ patients: a role for screening?
Lung cancer, COPD

12. Ongoing Work Within VACS The EXHALE Study
“EXamination of HIV Associated Lung Emphysema”
1. Compare risk factors for progression of COPD in HIV+ and HIV- veterans
Determine baseline prevalence, risk factors, characteristics and severity of COPD
Compare rate of progression (FEV1)
Relationship between rate of FEV1 decline with serum CD4 count and HIV viral load

13. EXHALE
2. Compare markers of oxidative stress and progression of OLD in HIV+ and HIV- smokers
Correlation with rate of decline in FEV1
Differences between HIV+ and HIV-
Relationship with CD4 and HIV viral load

14. EXHALE Subjects Sites: Atlanta, Bronx, Houston, LA VAMC
Subjects: 180 HIV+ and 180 HIV- patients
Current smoker
Non-current smoker
Subjects
<20 pkyrs
≥20 pkyrs
<20pkyrs
Total
HIV+ 45
180
HIV- 90
360

15. EXHALE (will fill in # below)
___ Consented
___ Questionnaires
___ Completed baseline PFTs
___ CT scans
___ 6-minute walk tests
___ Baseline blood draw
___ Exhaled Breath Condensates
___ Bronchoscopies

16. EXHALE Primary outcome Decrease in FEV1 (ml/year) Secondary outcomes
% with FEV1/FVC<70%
Worsening in stage of disease
Decrease in 6-minute walk test
Increase in self-reported dyspnea
Health care utilization for COPD, respiratory infections, overall mortality

17. EXHALE Results
Stay tuned….

18. Lung disease in HIV Conclusions
In addition to pneumonia, HIV is associated with increased risk for chronic lung disease, particularly COPD
Smoking is a major risk factor
Increased efforts at smoking cessation needed

19. Lung disease in HIV Conclusions
Particularly with improved survival from HIV, long term complications of smoking and sequelae of respiratory infections may lead to chronic respiratory impairment in many patients
Long term impact of HIV infection on lung health is largely still unknown

20. Acknowledgements Veterans Aging Cohort Study (VACS)
PI and Co-PI: AC Justice, DA Fiellin
Scientific Officer (NIAAA): K Bryant
Participating VA Medical Centers: Atlanta (D. Rimland), Baltimore (KA Oursler, R Titanji), Bronx (S Brown, S Garrison), Houston (M Rodriguez-Barradas, N Masozera), Los Angeles (M Goetz, D Leaf), Manhattan-Brooklyn (M Simberkoff, D Blumenthal, H Leaf, J Leung), Pittsburgh (A Butt, E Hoffman), and Washington DC (C Gibert, R Peck)
Core Faculty: K Mattocks (Deputy Director), K Akgun, S Braithwaite, C Brandt, K Bryant, R Cook, K Crothers, J Chang, S Crystal, N Day, R Dubrow, M Duggal, J Erdos, M Freiberg, M Gaziano, M Gerschenson, A Gordon, J Goulet, N Kim, M Kozal, K Kraemer, V LoRe, S Maisto, P Miller, P O’Connor, C Parikh, C Rinaldo, J Samet
Staff: H Bathulapalli, T Bohan, D Cohen, A Consorte, P Cunningham, A Dinh, C Frank, K Gordon, J Huston, F Kidwai, F Levin, K McGinnis, C Rogina, J Rogers, L Sacchetti, M Skanderson, J Tate, E Williams
Major Collaborators: VA Public Health Strategic Healthcare Group, VA Pharmacy Benefits Management, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Yale Center for Interdisciplinary Research on AIDS (CIRA), Center for Health Equity Research and Promotion (CHERP), ART-CC, NA-ACCORD, HIV-Causal
Major Funding by: National Institutes of Health: NIAAA (U10-AA13566), NIA (R01-AG029154), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347) , NIAID (U01-A ), NIMH (P30-MH062294), and the Veterans Health Administration Office of Research and Development (VA REA ) and Office of Academic Affiliations (Medical Informatics Fellowship).