NORTHWEST AIDS EDUCATION AND TRAINING CENTER

CROI 2015: Hot Topics in HIV Primary Care

Brian R. Wood, MDAssistant Professor of Medicine, University of WashingtonMedical Director, NW AETC ECHO

March 5, 2015

ECHO CROI Reviews 2015

3/5/15 3/12/15 3/19/15

Brian Wood: Primary Care

Shireesha Dhanireddy: New Treatments

Nina Kim: HCV Coinfection

Ruanne Barnabas: Prevention Issues

CROI 2015: Primary Care Topics

• Cancer risk and lung cancer screening• Benefits of statins beyond cholesterol reduction

“Cancers in Young and Old and Lung Cancer in HIV”

CROI 2015

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.

Cancer Type Hazard Ratio Comparing HIV+ to HIV- (95% CI)

Kaposi sarcoma 79.2 (42.9-146)

Non-Hodgkin lymphoma 3.01 (2.24-4.05)

Diffuse large B cell 5.56 (3.69-8.39)

Burkitt lymphoma 21.8 (6.91-68.5)

Other specified 1.16 (0.67-1.99)

Unspecified 6.78 (3.93-11.7)

Anus 32.4 (21.6-48.5)

Hodgkin lymphoma 9.96 (4.89-20.3)

Liver 3.83 (2.46-5.97)

Lung 1.52 (1.21-1.91)

Colorectal 0.97 (0.69-1.36)

Breast 0.96 (0.56-1.65)

Prostate 0.78 (0.61-0.99)

Total cancer

Prostate

Lung

NHL

Colorectal

Anal

0 2 4 6 8 10 12

Cancer Risk in HIV+ Over 65 Years Old

5-year cumulative incidence (%)

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.

CD4 Analysis Hazard Ratio (95% CI)

12-month lagged value

<200 1.6 (1.2-2.2)

200-500 1.2 (0.9-1.5)

12-month moving average

<200 2.0 (1.4-2.7)

200-500 1.4 (1.1-1.8)

24-month moving average

<200 1.7 (1.2-2.4)

200-500 1.3 (1.1-1.7)

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.

Ever smoked

CD4<200 HIV RNA >400

Clinical AIDS

0

5

10

15

20

25

30

35

40

Popu

lati

on

att

ributa

ble

ris

k (

PAF)

, %

Including lung cancerExcluding lung cancer

US Preventive Services Task Force (USPSTF) Lung Cancer Screening Recs

Ann Intern Med. 2014;160:330-338.

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 <350, current CD4 >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.

Patient Screen Detected

Histology Stage Age Pack years

Viral load

Last CD4

Nadir CD4

1 Yes Adeno IA 45 30 <40 637 160

2 Yes Adeno IV 48 52 <40 597 132

3 Yes Adeno IIA 49 45 <40 378 321

4 Yes Adeno IV 50 27 61 590 60

5 Yes Adeno IV 52 35 <40 568 236

6 Yes Adeno IA 52 60 43 859 214

7 Yes Squam IA 54 28 <40 345 71

8 Yes Adeno IB 56 34 <20 480 201

9 Yes No histo IA 58 21 <20 573 218

10 No Small cell Extended 50 40 <40 448 1

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

Benefits of Statins Beyond Cholesterol Reduction

CROI 2015

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

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-PLA2

• 80% progression with placebo

vs. 35% with atorvastatin

Lo J et al. Abstract 136.

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)

Weigh benefits against risks: hepatotoxicity, myopathy, drug interactions, polypharmacy, cost

Justice A et al. Lancet HIV, January 2015.

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)