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

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; 141:1356-72. 2. Rosen et al. AJRCCM 1997; 155:67-71. 3. Wallace et al. AJRCCM 1997; 155:72-80.

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; 118:890-98. Diaz et al. Annals of Int Med. 2000;132:369-372. 3. Grulich et al. AIDS 1999;13:839-843. 4. Grubb et al. AIDS 2006; 20:1095-1107.

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):374-83. 2. Page-Shafer et al. Ann Epidemiol 1996;6(5):420-30. 3. Galai et al. J Acquir Immune Defic Syndr Hum Retrovirol 1997;14(5):451-8. 4. Crothers et al. JGIM 2005; 20:1142-45.

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 1.01-2.13) by ICD-9 AOR* 1.58 (95% CI 1.14-2.18) 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): 1326-33

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

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

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

Unadjusted incidence per 1,000 PY

Age-stratified adjusted incidence rate ratios for pulmonary disease in HIV+ to HIV- Age <50 Age ≥50 Disease IRR IRR TB 6.0* 5.4* Bacterial PNA 5.1* 2.8* Lung cancer 2.1* 1.7* Fibrosis 1.6* 1.5* PAH 1.5* 1.6* COPD 1.2* 1.1* Asthma 1.0 0.9 Results similar in models adjusting for smoking *p<0.05

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

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

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

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

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

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

EXHALE Results Stay tuned….

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

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

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-A1069918), NIMH (P30-MH062294), and the Veterans Health Administration Office of Research and Development (VA REA 08-266) and Office of Academic Affiliations (Medical Informatics Fellowship).