1. N ORTHWEST A IDS E DUCATION AND T RAINING C ENTER CROI 2015: Hot Topics in HIV Primary Care Brian R. Wood, MD Assistant Professor of Medicine, University of Washington Medical Director, NW AETC ECHO March 5, 2015

2. ECHO CROI Reviews 2015 3/5/153/12/153/19/15 Brian Wood: Primary Care Shireesha Dhanireddy: New Treatments Nina Kim: HCV Coinfection Ruanne Barnabas: Prevention Issues

3. CROI 2015: Primary Care Topics Cancer risk and lung cancer screening Benefits of statins beyond cholesterol reduction

4. “Cancers in Young and Old and Lung Cancer in HIV” CROI 2015

5. Cancer Risk in HIV+ Over 65 Years Old Case-cohort study 5% Medicare registry sample All cancers in people over 65 in large cancer registry Association between HIV and cancer incidence Adjusted for age, race, sex, calendar year Yanik El et al. Abstract 725.

6. Cancer Risk in HIV+ Over 65 Years Old 5-year cumulative incidence (%)

7. CD4 Count as a Predictor of Lung Cancer Risk and Prognosis 26,065 HIV+ in VACS Incident non-small cell lung cancer cases Cox regression models for lung cancer risk, CD4 count Adjusted for: age, sex, race, smoking, h/o pneumonia or COPD Compared survival based on HIV status, CD4 +/- 200 Sigel K et al. Abstract 728.

8. Smoking Outweighs HIV-Related Risk Factors for Non-AIDS-Defining Cancers Adults in NA-ACCORD Non-AIDS-defining cancers HIV-related risk factors and smoking ≈40K adults, ≈160K person-years Most common cancers: lung (17%), anal (16%), prostate (10%), 9% HL, 7% liver, 7% breast Source. Althoff KN et al. Abstract 726. Population attributable risk (PAF), % Including lung cancer Excluding lung cancer

9. US Preventive Services Task Force (USPSTF) Lung Cancer Screening Recs Ann Intern Med. 2014;160:330-338.

10. Lung Cancer Screening in HIV+ Smokers 14 French clinical centers; single low-dose chest CT Inclusion: age >40, ever smoked in last 3 years, >20 pack- years, CD4 nadir 100 442 subjects: -Median age: 49.8, nadir CD4: 168, last CD4: 574 -90% with last viral load <50 -Median smoking pack-years: 30 94 subjects (21%) had a significant finding 18 diagnostic procedures in 15 subjects Makinson et al. Abstract 727.

11. Conclusions: Screening is safe and effective; USPSTF guidelines may miss early CA Questions: When to start screening? Which criteria- Age? Pack-years? CD4 nadir? Lung Cancer Screening in HIV+ Smokers

12. Benefits of Statins Beyond Cholesterol Reduction CROI 2015

13. 1) Overton ET et al. CID, May 2013. 2) Galli L et al. AIDS, Oct 2014.

14. Statin Reduces Non-Calcified Coronary Plaque Burden Double-blind, placebo-controlled, single-center, RCT Atorvasatatin vs. placebo 40 subjects, no known CAD, LDL 70-130, subclinical atherosclerosis (plaques) on CTA, stable on ART After 12 months, atorvastatin reduced non-calcified coronary plaque volume (-19.4% vs. +20.4%, p = 0.009) Reduced overall plaque volume, # of high-risk plaques, Lp-PLA 2 80% progression with placebo vs. 35% with atorvastatin Lo J et al. Abstract 136.

15. More Potential Statin Benefits Rosuvastatin arrests progression of carotid intima media thickness (Longenecker CT et al. Abstract 137) Simvastatin protects human aortic endothelial cells from oxidative damage (Panigrahi S et al. Abstract 298LB) Atorvastatin partially reverses the HIV-mediated reduction of heme oxygenase (HO-1) in macrophages and may have benefit in HAND (Duncan MR et al. Abstract 502) Statins improve SVR and reduce fibrosis progression and HCC among HCV+ persons (Butt AA et al. Abstract 643) Statins have initial benefit for BMD over placebo but benefit doesn’t persist at 96 weeks and has detrimental effects on insulin resistance (Erlandson KE et al. Abstract 771)

16. Weigh benefits against risks: hepatotoxicity, myopathy, drug interactions, polypharmacy, cost Justice A et al. Lancet HIV, January 2015.

17. Conclusions HIV infection raises risk of non-AIDS-defining malignancies, though smoking outweighs HIV-related risk factors Lung cancer screening should be considered for those at high risk, but need to define best criteria for HIV+ Statins have many potential benefits, including reduced progression of subclinical high-risk coronary plaques We need better guidelines for assessing CAD risk and statin initiation for HIV+ persons (A5332; reprievetrial.org)