Assessment of HIV Comorbidities

Andrew Carr, MBBS, MD, FRACP, FRCPAHIV, Immunology and Infectious Diseases UnitClinical Research Program, Centre for Applied Medical ResearchSt. Vincent’s Hospital and University of New South WalesSydney, Australia

Disclosures

• Research funding: Baxter, Gilead, MSD, Pfizer, ViiV• Consultancies: Gilead, MSD, ViiV• Lectures: BMS, Gilead, Janssen, MSD, Roche, ViiV• Advisory boards: Gilead, MSD, ViiV• Travel: BMS, Gilead, MSD, ViiV

Key Principles

Why comorbidities matter• More common cause of morbidity and mortality than AIDS in patients on ART• ART accelerates comorbidities that are common, eg, CVD, CKD, fractures• Increase complexity of care

– reduce ART adherence– reduce ART options– increase in polypharmacy for those ages 45+

• Reported in only ~25% of initial ART trials, and underassessed in routine care, so underappreciated

Gifford AL, et al. J Acquir Immune Defic Syndr. 2000;23(5):386-395; Presented by DAD study group at IAC. July 2010. Vienna, Austria. Hasse B, et al. Clin Infect Dis. 2011;53(11):1130-1139; Krentz HB, et al. Antivir Ther. 2012;17(5):833-840; Presented by Lee, et al. ADAP Data Report Workshop. 2012; Presented by Shahmanesh M, et al. ADAP Data Report Workshop. 2013.

Key Principles

When and Who• Pre-ART and pre-ART change in all patients• On ART

– every patient once stable (about 3 months)– test interval variable and proportional to ART type and to underlying risk in

individual patient– don’t order a test

if you don’t know what to do with the result if the result will not change management

• So, likely that most useful screening will be most useful in older HIV+ adults

Framingham risk score DAD risk scoreHow

Cardiovascular Disease

http://hp2010.nhlbihin.net/atpiii/calculator.asphttp://www.cphiv.dk/tools/dadriskequations/tabid/437/default.aspx

Who: ASCVD risk estimator

Cardiovascular Disease

Potential advantages• more current data• includes diabetes and race• provides 10-year and lifetime

estimates, including risks postintervention

http://tools.cardiosource.org/ASCVD-Risk-Estimator/

Potential disadvantages• source data

– only from USA– patients not HIV+

Calculator Period Outcome(s) Risk (%)Current Optimal

Framingham 10 years

myocardial infarction (MI) 5 ..

D:A:D 5 years MI 5 ..

ACC-AHA10 years

MI, ischemic stroke or CV death 8.1 2.1

Life-time

MI, ischemic stroke or CV death 50 5

Variable results with different equations

Cardiovascular Disease

• 50-year-old white man on LPV/r for 5 years• Total cholesterol = 5.5 mmol/L (99 mg/dL), HDL-C = 1.1 mmol/L (20 mg/dL)• Systolic BP = 125 mm Hg• Nonsmoker• Diabetes mellitus controlled

How

Method Baseline Week 4

Month 3/6/9/12 Annual

eGFR x x x x

Urine Protein:Creatinine ratio x x x

Blood pressure x x x

Diabetes? x x

Kidney Disease

http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf

Kidney Disease

How: assessing decline in eGFR• Assess other CKD risk factors, including:

– NSAID use– HCV, HBV– hypertension– diabetes

• Cobicistat/dolutegravir effects appear confined to initial 4 weeks• Falling eGFR after week 4 may be due to TDF

– urinary glucose/phosphate +– no dehydration– no creatine supplement– no active additional risk factors

http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf

HowFracture Risk

http://www.shef.ac.uk/FRAX; McComsey et al, Clin Infect Dis 2010; http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf

DXA FRAX 2º causesU.S. (2010)and EACS 2013

age >50,postmenopausal,fragility fracture

.. hypogonadism, hyperthyroid/parathyroid, chronic renal/liver disease

U.S. only .. T-score -2.5 to -1

BMI, alcohol, smoking, glucocorticosteroids,vitamin D

EACS only high fall risk,hypogonadism, systemic glucocorticosteroids

DXA + age >40

malabsorption, diabetes

DHHS No recommendation

Who

Fracture Risk

McComsey GA, et al. Clin Infect Dis. 2010 Oct 15;51(8):937-946.; http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf

HowHow Comment

HIV Dementia scale (HDS)• 3-5 minutes• insensitive for mild HAND• excellent specificity

International HDS• 2-3 minutes• anyone can use• insensitive for mild HAND

Total recall (Hopkins) • easy and quick• requires trained interpreter

Grooved pegboard • need normative data• requires trained interpreter

Executive interview • less sensitive• can confuse less education with HAND

MOS-HIV cognitive function • use as screen prior to neuropsych testing?

Neurocognitive Disease - HAND

Mind Exchange Working Group. Clin Infect Dis. 2013;56(7):1004-17

Who: HAND vs other causes of dementiaHow CommentHistory • long-term alcohol and drug use

CEBM/GOR D • exclude depression/anxiety/PTSD

CSF HIV viral load (LP) • <10% with plasma HIV RNA <50 will have detectable RNA in CSF

MRI • exclude other causes of dementia, eg, vascular/syphilis

Neuropsych testing • expensive• not generally available

Neurocognitive Disease - HAND

Mind Exchange Working Group. Clin Infect Dis. 2013;56(7):1004-17

Who and HowCancer Who How Interval

Anal MSM digital anal examPAP smear? 1-3 years

Breast women 50-70 years mammography 1-3 years

Cervix sexually active women PAP smear 1-2 years

Colorectal 50-75 years fecal occult blood test 1-3 years

Hepatoma cirrhosisHBV+

ultrasoundalpha-fetoprotein 6 months

Prostate men >50 years digital anal examPSA? 1-3 years

Cancer

http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf

WhoSymptomatic/Visible Toxicities

What IntervalOrgan CVD ACC-AHA (including diabetes) 1-2 years Renal eGFR / UProt:Cr / other causes 6 months Bone DXA / FRAX / other causes 2-5 years CNS Cogstate?; LP / MRI if symptomatic 12 monthsCancer Breast / bowel / lung / liver As in HIV-

Pap smear 1-2 yearsDrug d4T / AZT Lipoatrophy / fat accumulation 6 months PI GI symptoms every visit EFV CNS symptoms every visit RAL Muscle pain / weakness every visit

Summary

HIV Comorbidity Assessment