To interrupt or not to interrupt Are we SMART enough?

Transcription

1 SMART To interrupt or not to interrupt Are we SMART enough? highly active antiretroviral therapy

2 metabolism 50 copies/ml lipodystrophy [fat redistribution syndrome] lactic acidosis osteonecrosis ; avascular necrosis 25% metabolic syndrome National Cholesterol Education Program

3 SMART ; NCEP ATP-III 900 1,000 / ,000 / 6 7 The Strategies for Management of Antiretroviral Therapy SMART Study myocardial infarction

4 250 cells/ SMART L SMART 350 cells/ L 15% National Institute of Allergy and Infectious Diseases double blind primary end point 350 cells/ L secondary end point Viral suppression [VS] group Drug conservation [DC] group

5 SMART 400 copies/ml [high-density lipoprotein cholesterol; HDL-C] [protease 6, inhibitor] % Data Safety and Monitoring Board 24% ,472 2,752 2, % 5,

6 8.6% 1.8% 87 cells/ L 400 copies/ml 28.8% 72.3% 209 cells/ L copies/ml 71.8% 6.0% % copies/ml cells/ L 39.2% 33.4% esophageal candidiasis 20.0% Pneumocystis jirovecii pneumonia 93.7% 350 cells/ L 57.4% 14.9% 67.9% 92.7% 250 cells/ L

7 SMART % copies/ml ml 400 copies/ 8% 0.8 per 100 person-years 2.6 per 100 PY 3.2 per 100 PY 3.1 per 100 PY % latest, updated % % copies/ml copies/ml copies/ml

8 500 cells/ L 400 copies/ml 29% 66% % 400 copies/ml 140 cells/ L cells/ L 95%

9 SMART B lamivudine 3TC B cytokine C- highly sensitive C-reactive protein; hscrp [95%

10 1.5] % 5, % active smoking 3.0 per 1,000 PY; 0.5 per 1, % non-hodgkin, s lymphoma 3.0 Streptococcus pneumoniae 000 PY Kaposi, s sarcoma (communityacquired pneumonia) Staphylococcus aureus Haemophilus influenzae

11 SMART 31% 400 copies/ml 36% 34% % 883 gonorrhea 58% 2 Chlamydia syphilis 18% 15.4% 1,500 copies/ml % 55% 14% 47% 45

12 ,500 copies/ml Item Survey 1,225 Short-Form

13 SMART didanosine ddi abacavir ABC 1.Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced immunodeficiency virus infection. N Engl J Med 1998;338: Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet 1998;352: Mocroft A, Ledergerber B, Katlama C, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 2003;362: Hung CC, Hsiao CF, Chen MY, et al. Improved survival of persons with human immunodeficiency virus type 1 infection in the era of highly active antiretroviral therapy in Taiwan. Jpn J Infect Dis 2006 ; 59: Yang CH, Huang YF, Hsiao CF, et al. Trends of mortality and causes of deaths among HIV-infected patients in Taiwan, HIV Med 2008;9: Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000;356: Brown TT, Cole SR, Li X,et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med 2005 ;165: Ledergerber B, Furrer H, Rickenbach M, et al. Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss Cohort Study. Clin Infect Dis 2007;45: Lo YC, Chen MY, Sheng WH, et al. Risk factors of incident diabetes mellitus among HIV-Infected individuals receiving combination antiretroviral therapy in Taiwan: a case-control study. HIV Med ( revised) 10.Friis-M?ller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007;356: The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. + count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355: The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. Inferior clinical outcome of the + cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of + cell counts and HIV RNA levels during follow-up. J Infect Dis 2008;197: The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. Major clinical outcomes in antiretroviral therapy (ART)-na?ve participants and in those not receiving ART at baseline in the SMART study. J Infect Dis 2008;197: The SMART Study Group. Risk for opportunistic disease and death after 47

14 reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy. A randomized trial. Ann Intern Med 2008;149: Strategies for Management of Antiretroviral Therapy/INSIGHT/DAD Study Group. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS 2008;22:F17-24.Carr A, Grund B, Neuhaus J, et al. Asymptomatic myocardial ischaemia in HIV-infected adults. AIDS 2008;22: Phillips AN, Carr A, Neuhaus J, et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther 2008;13: Gordin EM, Roediger MP, Girard PM, et al. Pneumonia in HIV-infected persons. Increased risk with cigarette smoking and treatment interruption. Am J Resp Crit Care Med 2008;178: Silverberg MJ, Neuhaus J, Bower M, et al. Risk of cancers during interrupted antiretroviral therapy in the SMART study. AIDS 2007;21; Burman W, Grund B, Neuhaus J, et al. Episodic antiretroviral therapy increases HIV transmission risk compared with continuous therapy: results of a randomized controlled trial. J Acquir Immune Defic Syndr 2008;Sep Burman WJ, Grund B, Roediger MP, et al. The impact of episodic cell countguided antiretroviral therapy on quality of life. J Acquir Immune Defic Syndr 2008 ;47: