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Assessment of HIV Comorbidities Andrew Carr, MBBS, MD, FRACP, FRCPA HIV, Immunology and Infectious Diseases Unit Clinical Research Program, Centre for Applied Medical Research St. Vincent’s Hospital and University of New South Wales Sydney, 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 Cardiovascular Disease How Framingham risk score http://hp2010.nhlbihin.net/atpiii/calculator.asp http://www.cphiv.dk/tools/dadriskequations/tabid/437/default.aspx DAD risk score Cardiovascular Disease Who: ASCVD risk estimator Potential advantages Potential disadvantages • more current data • • includes diabetes and race – only from USA • provides 10-year and lifetime estimates, including risks postintervention – patients not HIV+ http://tools.cardiosource.org/ASCVD-Risk-Estimator/ source data Cardiovascular Disease Variable results with different equations • 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 Calculator Period Outcome(s) Risk (%) Current Optimal Framingham 10 years D:A:D ACC-AHA myocardial infarction (MI) 5 years MI 5 .. 5 .. 10 years MI, ischemic stroke or CV death 8.1 2.1 Lifetime MI, ischemic stroke or CV death 50 5 Kidney Disease How Baseline Week 4 Month 3/6/9/12 Annual eGFR x x x x Urine Protein:Creatinine ratio x x x Blood pressure x Diabetes? x Method http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf x x x 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 Fracture Risk How http://www.shef.ac.uk/FRAX; McComsey et al, Clin Infect Dis 2010; http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf Fracture Risk Who DXA U.S. (2010) age >50, and EACS 2013 postmenopausal, fragility fracture FRAX .. 2º causes hypogonadism, hyperthyroid/parathyroid, chronic renal/liver disease U.S. only .. T-score -2.5 to -1 EACS only high fall risk, DXA + age hypogonadism, >40 systemic glucocorticosteroids No recommendation BMI, alcohol, smoking, glucocorticosteroids, vitamin D malabsorption, diabetes DHHS McComsey GA, et al. Clin Infect Dis. 2010 Oct 15;51(8):937-946.; http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf Neurocognitive Disease - HAND How How 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? Mind Exchange Working Group. Clin Infect Dis. 2013;56(7):1004-17 Neurocognitive Disease - HAND Who: HAND vs other causes of dementia How Comment History • 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 Mind Exchange Working Group. Clin Infect Dis. 2013;56(7):1004-17 Cancer Who and How Cancer Who How Interval Anal MSM digital anal exam PAP 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 cirrhosis HBV+ ultrasound alpha-fetoprotein 6 months Prostate men >50 years digital anal exam PSA? 1-3 years http://www.eacsociety.org/Portals/0/Guidelines_Online_131014.pdf Symptomatic/Visible Toxicities Who HIV Comorbidity Assessment Summary What Interval 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 months Breast / bowel / lung / liver As in HIV- Pap smear 1-2 years d4T / AZT Lipoatrophy / fat accumulation 6 months PI GI symptoms every visit EFV CNS symptoms every visit RAL Muscle pain / weakness every visit Organ Cancer Drug