case-based panel discussion led by carl knud schewe infektionsmedizinisches centrum hamburg

CASE-BASED PANEL DISCUSSIONLed by Carl Knud ScheweInfektionsmedizinisches Centrum Hamburg

BONE AND RENAL COMORBIDITIES IN HIV: THE OSTEO-RENAL EXCHANGE PROGRAM 4

Test question: Interactive System

On what continent are you currently practicing?

1. Africa

2. Asia

3. Australasia

4. Europe

5. North America

6. South America


Bone Case: General Question for the Audience

In your clinic, are you screening for osteopenia/osteoporosis in your HIV-infected patients?

1. No

2. Yes, on a case by case basis, but not systematic

3. Yes, systematic with FRAX® score and if required a DXA scan


Bone Case

56 years old, retired accountant, MSM HIV diagnosed in 1989:• No opportunistic infections• ARV treatment since 1996

Comorbid conditions: • Chronic hepatitis B, hypertension, hyperlipidemia, polyneuropathy,

chronic back painPrevious smoker, 40 pack years, 4–5 beers per weekMedication: • Aspirin 100 mg, pravastatin, ramipril, amlodipine, HCTZ, diclofenac,

metamizole*, omeprazole* Novaminsulfon (metamizole) is not approved in Australia


Bone Case: ARV History

Date ART VL CD4+7/1996 AZT 3TC 80,000 350 failure2/1998 AZT 3TC SQV ? ? failure6/1998 CBV NLF ? ? diarrhea, failure1/1999 EFV d4T DDI ? ? depression3/1999 ABC 3TC d4T ? ? failure3/2001 RTV 400 SQV 400 ? ? diarrhea3/2001 EFV d4T ABC 15,000 530 failure9/2002 ARV interruption 6 log10 427 K103N2002–2010 LPV/r SQV TDF 3TC <50 603 HBV DNA neg.


Bone Case

Physical examination:• Height 180 cm, weight 69 kg, BMI 21.3, BP 140/100 mmHg, 56 beats/min,

looking older, diminished breath sounds, absent ankle reflexes

Laboratory: • Cholesterol 190 mg/dL (4.91 mmol/L)• Triglycerides 220 mg/dL (2.48 mmol/L)• LDL 102 mg/dL (2.63 mmol/L)• HDL 32 mg/dL (0.83 mmol/L)• Creatinine 1.2 mg/dL (106 µmol/L)

Is this patient at increased risk of fragility fracture?


Bone Case: Question 1

Is this patient at increased risk of fragility fracture?

1. Low: <10% 10-year risk of major fracture

2. Moderate: 10–20% 10-year risk of major fracture

3. High: >20% 10-year risk of major fracture


Bone Case: FRAX® Score

Should HIV be considered a cause of secondary osteoporosis?

http://www.shef.ac.uk


Bone Case: FRAX® Score



Bone Case: Do we need a DXA Scan?

Assessment threshold – major fracture



Bone Case: We do a DXA Scan!



Bone Case: DXA Scan Tips the Balance

Intervention threshold

Do we need additional diagnostic tests? • Vitamin D? • Bone turnover markers?



Bone Case: Question 2

How would you manage this patient in addition to lifestyle interventions?

1. Calcium + Vitamin D

2. Calcium + Vitamin D + Bisphosphonate

3. Calcium + Vitamin D + ARV-switch

4. Calcium + Vitamin D + Bisphosphonate + ARV-switch


Bone Case: ARV History

Date ART VL CD4+7/1996 AZT 3TC 80,000 350 failure2/1998 AZT 3TC SQV ? ? failure6/1998 CBV NLF ? ? diarrhea, failure1/1999 EFV d4T DDI ? ? depression3/1999 ABC 3TC d4T ? ? failure3/2001 RTV 400 SQV 400 ? ? diarrhea3/2001 EFV d4T ABC 15,000 530 failure9/2002 ARV interruption 6 log10 427 K103N2002–2010 LPV/r SQV TDF 3TC <50 603 HBV DNA neg.


Bone Case: Follow Up

Switch to:• Maraviroc 2x150 mg, lopinavir/ritonavir 2x400/100 mg,

raltegravir 2x200 mg• Entecavir 1 mg (!)


Minimum Prescribing Information: Kaletra Tablets & Oral Solution (LPV/r)Please review full Product Information / Data Sheet before prescribing. Full Product Information / Data Sheet is available on request from AbbVie

Pty Ltd, ABN 48 156 384 262. 32–34 Lord Street, Botany NSW 2019 / AbbVie Ltd. 156–158 Victoria St, Wellington, 6011 New Zealand

INDICATIONSFor the treatment of HIV-infection in combination with other antiretroviral drugs in adults and children aged 2 years and older.CONTRAINDICATIONSKnown hypersensitivity to any of the ingredients in Kaletra, co-administration with medicines highly dependent on CYP3A for clearance: alfuzosin

hydrochloride, fusidic acid, astemizole, terfenadine, blonanserin, midazolam, triazolam, ergotamine, dihydroergotamine, ergometrine, methylergometrine, cisapride, St John’s Wort (Hypericum perforatum), lovastatin, simvastatin, salmeterol, pimozide or sildenafil (for the treatment of high blood pressure in the vessels in the lung). Kaletra Oral Solution only: children below 2 years of age, pregnancy, hepatic and renal impairment, patients treated with disulfiram or metronidazole.

PRECAUTIONSNew onset and exacerbation of diabetes mellitus, hyperglycaemia, use in mild to moderate hepatic impairment, fat redistribution,

hyperlipidaemia, increased risk of pancreatitis, immune reconstitution syndrome, autoimmune disorders, PR interval prolongation, Pregnancy: Cat B3. Due to the potential for HIV transmission and serious adverse reactions in nursing infants, mothers should be instructed not to breast feed whilst on Kaletra.

ADVERSE EFFECTSMild to moderate diarrhoea; nausea; lipodystrophy; abdominal pain; asthenia; abnormal stools; headache; dyspepsia; vomiting; rash; abdomen

enlarged; hypercholesterolaemia; hyperlipidaemia; increased liver enzymes; hyperglycaemia; hyperuricaemia. See full PI/Data Sheet.INTERACTIONSCo-administration with drugs and herbal products primarily metabolised by CYP3A (dihydropyridine calcium channel blockers,

immunosuppressants and erectile dysfunction agents), or are inducers or inhibitors of CYP3A (anticonvulsants, corticosteroids, antifungals and rifamycins).

Date of preparation: 30 April 2014, based on PI last updated on 24 April 2014, version 18


Minimum Prescribing Information: Kaletra Tablets & Oral Solution (LPV/r)INTERACTIONS continuedOther drugs include fentanyl, antiarrhythmics (digoxin, amiodarone, systemic lignocaine and quinidine), anticancer agents (dasatinib, nilotinib,

vincristine, and vinblastine), anticoagulants (warfarin, rivaroxaban), anticonvulsants (phenobarbital, phenytoin, carbamazepine, lamotrigine, valproate), antipsychotics (quetiapine), antidepressants (trazodone and bupropion), antifungals (ketoconazole, itraconazole, voriconazole), HCV protease inhibitor (boceprevir), disulfiram, metronidazole, methadone, colchicine, bosentan, and oral and patch contraceptives.

Other anti-HIV medications including other protease inhibitors.DOSAGE AND ADMINISTRATIONKaletra Tablets : Tablets may be taken with or without food and should be swallowed whole and not chewed, broken or crushed.Dosage: 200 mg lopinavir/50 mg ritonavir tablets : Adults and children ≥ 35kg two tablets twice daily. Kaletra tablets may also be administered as four tablets once daily in adult patients with less than three lopinavir associated mutations. Kaletra

should not be taken once daily with efavirenz, nevirapine, nelfinavir, amprenavir, carbamazepine, phenobarbital and phenytoin.100 mg lopinavir/25mg ritonavir tablets: Children < 45 kg dosage is based on body weight. (See full PI/Data Sheet for dosing guidelines).Kaletra Oral Solution (80 mg lopinavir/20 mg ritonavir per mL) Dosage:Adults: 5mL of oral solution (400/100mg) twice daily taken with food. Kaletra oral solution may also be administered as 10mL once daily in adult patients with less than three lopinavir associated mutations. Kaletra

should not be taken once daily with efavirenz, nevirapine, nelfinavir, amprenavir, carbamazepine, phenobarbital and phenytoin.Children: 2 years and older: 230/57.5mg/m2 (or 12/3 mg/kg for children <15 kg or 10/2.5 mg/kg for children ≥15kg) twice daily taken with food,

up to a maximum dose of 400/100mg (5mL) twice daily. With concomitant nevirapine or efavirenz, should consider increasing dosage to 300/75 mg/m2 (or 13/3.25 mg/kg for children <15 kg

or 11/2.75 mg/kg for children ≥15 kg) twice daily taken with food. (See full PI/Data Sheet for dosing guidelines).

AbbVie Pty Ltd, 32–34 Lord Street, Botany NSW 2019, Australia or AbbVie Ltd, Level 6, 156–158 Victoria Street, Wellington, New Zealand. Date of preparation: 30 April 2014, based on PI last updated on 24 April 2014, version 18


Renal Case

22 year old, fashion designer, MSM

Caucasian/African

HIV diagnosis 2012, CD4+ nadir 360 cells/mm3, VL 76,000 c/mL

ARV initiated in 2013: FTC/RPV/TDF• Serum creatinine 1.2 mg/dL (106 µmol/L), no urinary or other laboratory

abnormalities

January 2014: Discontinuation of FTC/RPV/TDF, problem with concomitant food intake• Switch to EVG/COBI/FTC/TDF • April 2014 first presentation at ICH-Hamburg for refill of ARV medication


Renal Case

No complaints, tolerates EVG/COBI/FTC/TDF well

Moves to Hamburg for new job

No time for laboratory testing after switch to EVG/COBI/FTC/TDF

Physical exam: • Healthy young man• BMI 20.5• Blood pressure 115/80 mmHg• HR 64 beats/minute• No other abnormalities

What kind of monitoring would you perform?


Renal Case: Question 1

What tests would you perform to screen for renal abnormalities in this patient?

1. Serum creatinine and urine dipstick

2. Estimated GFR and urine dipstick

3. Estimated GFR, urine dipstick, serum phosphate

4. Estimated GFR, urine dipstick, serum phosphate, renal ultrasound

5. Other


Renal Case continued

Serum creatinine 1.6 mg/dL (141 µmol/L)

eGFR by MDRD 56 mL/min

No abnormalities in urine dipstick

Question 2: What further workup is necessary?


Renal Case: Question 2

What tests should be done for further workup?

1. Renal ultrasound

2. 24 hours urine collection creatinine clearance

3. Albumin/creatinine ratio and protein/creatinine ratio in morning urine

4. Fractional excretion of phosphate

5. All of the above tests


Renal Case continued

Normal diet, no creatinine supplements, no abuse of drugs, no over the counter use of NSAIDs, no family history of kidney disease

Extended laboratory tests: No inflammatory markers, no markers of autoimmune disease or monoclonal gammopathy

Ultrasound: Kidneys of normal size and renal parenchyma, no obstruction

Serum creatinine: 1.75 mg/dL (155 µmol/L)

24 hours urine collection: creatinine clearance: 67 mL/min

Fractional excretion of phosphate and protein/creatinine ratio normal

THANK YOU

BONE AND RENAL COMORBIDITIES IN HIV: THE OSTEO-RENAL EXCHANGE PROGRAM

A1450569

AbbVie Pty Ltd. 32-34 Lord St, Botany NSW 2019, Australia. July 2014. AU-KAL-2014-5

case-based panel discussion led by carl knud schewe infektionsmedizinisches centrum hamburg

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