第 22 回日本ｴｲｽﾞ学会教育セッション Improving the Management of HIV Diseases Interactive Session Nov. 27, 2008 The 22 nd Annual Meeting of the JSAR Evening Seminer 3 Plannning ： HIV Care Management Initiative-Japan Co-hosting ： The 22 nd Annual Meeting of the JSAR/GSK

第 22 回日本ｴｲｽﾞ学会教育セッション Cases studies Professor David A Cooper NCHECR November 2008

第 22 回日本ｴｲｽﾞ学会教育セッション Case 1- IF 47 year old Caucasian man diagnosed with HIV 1986 CDC B nadir CD4+ cell count: 252/µL pre treatment VL: 376,100 c/mL alcohol and recreational drug use including speed hep B sAg negative, cAb positive hepatitis C negative

第 22 回日本ｴｲｽﾞ学会教育セッション previous regimens: d4T + 3TC ABC + IDV/rNov May 2001 ABC + LPV/rMay Sep 2004 ABC + fAPV/rAug Jan 2007 AZT + 3TC + ATV/rJan HIV had been suppressed all the time. Case 1- IF

第 22 回日本ｴｲｽﾞ学会教育セッション October 2007: fatigue and right upper quadrant pain Case 1 - IF

第 22 回日本ｴｲｽﾞ学会教育セッション What is the cause of his hepatitis? 1) reactivation of hepatitis B 2) acute hepatitis C 3) alcoholic hepatitis 4) pancreatitis 5) lactic acidosis Case 1 - IF

第 22 回日本ｴｲｽﾞ学会教育セッション What is the cause of his hepatitis? 1) reactivation of hepatitis B 2) acute hepatitis C 3) alcoholic hepatitis 4) pancreatitis 5) lactic acidosis Case 1 - IF

第 22 回日本ｴｲｽﾞ学会教育セッション hepatitis B DNA:negative hepatitis C viral load: 700,000 c/mL lactate: 1.6 mmol/L glucose: 4.2 mmol/L cholesterol:1.5 mmol/L HDL-chol:0.7 mmol/L LDL-chol:0.2 mmol/L triglycerides: 2.1 mmol/L Case 1- IF

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat his acute HCV? 1) wait and see 2) PEG-IFN 3) PEG-IFN + RBV 4) intensify ART 5) something else Case 1- IF

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat his acute HCV? 1) wait and see 2) PEG-IFN 3) PEG-IFN + RBV 4) intensify ART 5) something else Case 1- IF

第 22 回日本ｴｲｽﾞ学会教育セッション Case 1- IF HCV spontaneously cleared September 2008

第 22 回日本ｴｲｽﾞ学会教育セッション What percentage of HIV-infected persons with acute HCV spontaneously clear? 1) 1-2% 2) 10-20% 3) 50-60% 4) % Case 1- IF

第 22 回日本ｴｲｽﾞ学会教育セッション What percentage of HIV-infected persons with acute HCV spontaneously clear? 1) 1-2% 2) 10-20% 3) 50-60% 4) % Case 1- IF

第 22 回日本ｴｲｽﾞ学会教育セッション year old Caucasian man diagnosed with HIV 1985 AIDS CDC C3 PJP 1994 treated with pentamidine and corticosteroids CMV retinitis 1997 treated with GCV and cidofovir NHL 2002 treated with CHOP and high dose methotrexate Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション pre ART: CD4+ cells: 60/µL viral load:310,900 c/mL previous regimens AZT+ddCJan Oct 1995 AZT+3TC+lovirideOct Mar 1996 ddI+d4T+3TC+lovirideMar Sep 1996 d4T+DLV+SQVJan May 2002 d4T+ABC+3TC+DLV+SQVMay Jul 2004 Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション Case 2- MB August 2003 urea 4.9 mmol/L creatinine90 µmol/L

第 22 回日本ｴｲｽﾞ学会教育セッション He has developed severe lipodystrophy. What regimen would you choose? 1) AZT+3TC+EFV 2) TDF+3TC+EFV 3) TDF+3TC+LPV/r 4) ABC+3TC+EFV 5) ABC+3TC+LPV/r Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション He has developed severe lipodystrophy. What regimen would you choose? 1) AZT+3TC+EFV 2) TDF+3TC+EFV 3) TDF+3TC+LPV/r 4) ABC+3TC+EFV 5) ABC+3TC+LPV/r Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション changed to TDF+ABC+3TC+DLV+SQV develops severe narcotic dependent pain in wrists and knees Case 2- MB August 2005 urea 10.1 mmol/L creatinine246 µmol/L

第 22 回日本ｴｲｽﾞ学会教育セッション regiondate measured BMD (g/cm 2 ) change vs baseline (%) young-adultage-matched %T- score %Z- score right femurMay August spine: L2- L4 May August Case 2- MB Bone densitometry August 2005

第 22 回日本ｴｲｽﾞ学会教育セッション spine Case 2- MB Bone densitometry August 2005 right femur left femur

第 22 回日本ｴｲｽﾞ学会教育セッション What is the cause of the renal failure and bone pain? 1) TDF 2) HIV nephropathy 3) TDF and previous pentamidine 4) previous cidofovir and corticosteroids 5) TDF and previous cidofovir Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション What is the cause of the renal failure and bone pain? 1) TDF 2) HIV nephropathy 3) TDF and previous pentamidine 4) previous cidofovir and corticosteroids 5) TDF and previous cidofovir Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション Case 2- MB ceased TDF August 2005 new regimen: ABC+3TC+DLV+SQV ceased tenofovir October 2008 urea 10 mmol/L creatinine161 µmol/L

第 22 回日本ｴｲｽﾞ学会教育セッション Renal biopsy was performed December What changes would you expect to see in the renal biopsy? 1) tubular toxicity 2) interstitial nephritis 3) collapsing glomerulopathy 4) glomerulosclerosis 5) glomerular and tubular disease Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション Renal biopsy was performed December What changes would you expect to see in the renal biopsy? 1) tubular toxicity 2) interstitial nephritis 3) collapsing glomerulopathy 4) glomerulosclerosis 5) glomerular and tubular disease Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション renal biopsy showed severe interstitial fibrosis globally sclerosed glomeruli tubular degeneration BK polyoma viral inclusions Case 2- MB

第 22 回日本ｴｲｽﾞ学会教育セッション year old Asian man diagnosed with HIV 1991 AIDS CDC B1 mild type 2 diabetes 1998 works as a chef Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション pretreatment CD4+ cells: 207/µL viral load:40,000 c/mL previous regimens d4T+3TC+SQVFeb Sep 1997 d4T+3TC+NVPSep Nov 1997 d4T+ddI+NVPNov Jan 1998 d4T+ddIJan Apr 1998 Jul Nov 1998 Feb Oct 1999 EFV+IDV/rOct Mar 2002 EFV+ATV/r Mar HIV had been suppressed with EFV Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション Case 3- EN metabolic profile February August 2003 August 2003 triglycerides 7.4 mmol/L cholesterol 5.6 mmol/L HDL-chol 1.17 mmol/L glucose 11.5 mmol/L HbA1c 8.6%

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat the dyslipidemia? 1) diet 2) fibrate 3) statin 4) fibrate and statin 5) metformin and statin Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat the dyslipidemia? 1) diet 2) fibrate 3) statin 4) fibrate and statin 5) metformin and statin Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション ceased gemfibrozil due to myopathy February 2005 Case 3- EN started gemfibrozil commenced fibrate October 2003 February 2005 triglycerides 2.1 mmol/L cholesterol 5.9 mmol/L HDL-chol 1.7 mmol/L glucose 8.1 mmol/L HbA1c 8.1%

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat dyslipidaemia now? 1) diet 2) metformin 3) statin 4) statin and ezetimibe 5) switch regimen Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat dyslipidaemia now? 1) diet 2) metformin 3) statin 4) statin and ezetimibe 5) switch regimen Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション Case 3- EN started pravastatin commenced pravastatin February 2005 October 2006 triglycerides 14 mmol/L cholesterol 8 mmol/L HDL-chol 0.8 mmol/L glucose 9.3 mmol/L HbA1c 6.9%

第 22 回日本ｴｲｽﾞ学会教育セッション What would you do now? 1) change to more potent statin 2) add insulin to pravastatin 3) add metformin to pravastatin 4) add ezetimibe to pravastatin 5) switch ART regimen to lipid neutral drugs Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション What would you do now? 1) change to more potent statin 2) add insulin to pravastatin 3) add metformin to pravastatin 4) add ezetimibe to pravastatin 5) switch ART regimen to lipid neutral drugs Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション Case 3- EN started rosuvastatin commenced rosuvastatin February 2007 November 2007 triglycerides 10.8 mmol/L cholesterol 6.1 mmol/L HDL-chol 0.9 mmol/L glucose 6.1 mmol/L HbA1c 5.9%

第 22 回日本ｴｲｽﾞ学会教育セッション Decided to change regimen. What would you recommend? 1) TDF+FTC+EFV 2) TDF+FTC+ATV 3) ABC+3TC+ATV 4) TDF+FTC+ATV/r 5) ATV + raltegravir Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション Decided to change regimen. What would you recommend? 1) TDF+FTC+EFV 2) TDF+FTC+ATV 3) ABC+3TC+ATV 4) TDF+FTC+ATV/r 5) ATV + raltegravir Case 3- EN

第 22 回日本ｴｲｽﾞ学会教育セッション Case 3- EN started ATV + raltegravir commenced ATV + raltegravir November 2007 August 2008 triglycerides 0.9 mmol/L cholesterol 3.4 mmol/L HDL-chol 1.1 mmol/L glucose 3.4 mmol/L HbA1c 5.1%

第 22 回日本ｴｲｽﾞ学会教育セッション Case 4- RVB 60 year old Caucasian man diagnosed with HIV 1982 nadir CD4+ cell count: 96/µL

第 22 回日本ｴｲｽﾞ学会教育セッション Case 4- RVB previous regimens: AZT monotherapy: Aug Nov 1994 Jan Aug 1995 AZT+ delavirdine:Nov Jan 1995 d4T monotherapy:Aug Aug 1996 d4T+3TC+IDV:Aug Nov 1996

第 22 回日本ｴｲｽﾞ学会教育セッション August 1996PJP diagnosis treated with pentamidine November 1996 muscle wasting weight loss glucose: 26 mmol/L triglycerides: 7.3 mmol/L cholesterol: 3.6 mmol/L HbA1C: 10.9% Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション What is the most likely cause of his diabetes mellitus? 1) protease inhibitor therapy 2) mitochondrial toxicity from TANRTIs 3) pentamidine therapy 4) pancreatitis from hypertriglyceridemia 5) hepatitis C Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション What is the most likely cause of his diabetes mellitus? 1) protease inhibitor therapy 2) mitochondrial toxicity from TANRTIs 3) pentamidine therapy 4) pancreatitis from hypertriglyceridemia 5) hepatitis C Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション He was treated with insulin which was stopped in 1999 HCV was positive in 1998 After stopping his fasting chemistry is glucose: 8.8 mmol/L HbA1C:8% cholesterol: 6.2 mmol/L HDL-chol: 0.6 mmol/L triglycerides: 18.3 mmol/L Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat his diabetes? 1) diet 2) insulin 3) oral hypoglycaemics 4) treat hepatitis C Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション How would you treat his diabetes? 1) diet 2) insulin 3) oral hypoglycaemics 4) treat hepatitis C Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション He is now stable on ABC + 3TC + NVP No diabetes therapy Hepatitis C treated with PEG-IFN + RBV in April 2001 with SVR Case 4- RVB Aug 2006 triglycerides 29 mmol/L cholesterol 11 mmol/L HDL-chol 2 mmol/L glucose 8 mmol/L HbA1c 6.8% stopped Pravastatin due to severe headache

第 22 回日本ｴｲｽﾞ学会教育セッション What changes would you make to his management now? 1) no change 2) oral hypoglycaemics 3) oral hypoglycaemics + fibrate 4) fibrate 5) fibrate + statin Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション What changes would you make to his management now? 1) no change 2) oral hypoglycaemics 3) oral hypoglycaemics + fibrate 4) fibrate 5) fibrate + statin Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション started fenofibrate October 2006 started metformin and rosiglitazone July 2007 Case 4- RVB rosiglitazone + metformin fenofibrate June 2008 triglycerides 34.8 mmol/L cholesterol 12.3 mmol/L HDL-chol 3.6 mmol/L glucose 11.9 mmol/L HbA1c 8.1% stopped Pravastatin due to severe headache

第 22 回日本ｴｲｽﾞ学会教育セッション How would you manage his dyslipidaemia now? 1) stop oral hypoglycaemics and continue fibrate only 2) stop oral hypoglycaemics and add potent statin to fibrate 3) keep oral hypoglycaemics and fibrate and add potent statin 4) change to insulin and continue fibrate 5) give metformin and rosuvastatin Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション How would you manage his dyslipidaemia now? 1) stop oral hypoglycaemics and continue fibrate only 2) stop oral hypoglycaemics and add potent statin to fibrate 3) keep oral hypoglycaemics and fibrate and add potent statin 4) change to insulin and continue fibrate 5) give metformin and rosuvastatin Case 4- RVB

第 22 回日本ｴｲｽﾞ学会教育セッション insulin restarted in June 2008 ACE inhibitor and aspirin added Case 4- RVB insulin October 2008 triglycerides 4.7 mmol/L cholesterol 5.7 mmol/L HDL-chol 0.9 mmol/L glucose 5.1 mmol/L HbA1c 6.3 mmol/L