1. Problems of HIV Infection in the HAART Era Akihiko Suganuma M.D. Tokyo Metropolitan Komagome Hospital Department of Infectious Diseases

2. Tokyo Metropolitan Komagome Hospital Total accumulated HIV patients (1985-2012) : 2292 cases Annual new HIV patients (2012) : 93 cases Annual in-patients with HIV (2012) : 120 cases

3. Outline 1. HIV Trends in Komagome Hospital 2. Malignancies and HIV 3. Metabolic Complications and HIV 4. Caregiving in People Living with HIV

4. HIV Trends in Komagome Hospital

5. HIV Trends in Japan Reported Number of New HIV Cases Composition of Transmission Routes 55% 22% MSM: Men who Have Sex with Men

6. Gender and Transmission Routes - Komagome hospital- Male 1968 Female 261 Heterosexual 93% Hemophilia 0.8% Blood transfusion 0.8% Others 3% Unknown 2% MSM 67% Heterosexual 33% Hemophilia 2.5% Blood transfusion 0.2% Unknown 6.4% Others 1.3%

7. Life Expectancy of HIV Patients Ann Intern Med. 2007; 146: 87-95 HIV Without HCV - Life expectancy of 25-year-old people Non-HIV years

8. Age Mean Age of HIV Patients at Death -Komagome hospital- 1985-1996 1997-2001 2002-20072008-2012

9. Age Distribution -Komagome hospital- （ n=672 ） 132 228 145 40 16 111 296(44%) 9

10. HIV Patient who has Long-Term Survival JAMA. 2013; 309: 1397–1405 Mr. H is a 74-year-old man who was diagnosed with HIV in 1984. He received a total of 7 NRTIs and 6 PIs before starting his current regimen. His current status is CD4 440 cell/μL and undetectable viral load. He has hypertension, hyperlipidemia, osteoporosis, depression, chronic kidney disease, and past anal squamous cell carcinoma.

11. Malignancies and HIV

12. Causes of Death - Komagome hospital- AIDS defining disease Liver disease Non-AIDS defining cancer Bacterial disease unknown

13. Causes of Death in HIV Patients on HAART -Komagome hospital- - Malignant lymphoma 7 - Hepatocelluer carcinoma 5 Total 55 (Male 51) Mean age at death 53.9 yrs. Malignancy 32 (58%) (No., %)

14. HIV/AIDS associated cancer AIDS defining cancer(ADC) Malignant lymphoma Kaposi sarcoma Cervical cancer Non-AIDS defining cancer(NADC) The others AIDS. 2008 ; 22: 489-496 Non-Hodgkin lymphoma/ Primary central nervous system lymphoma

15. HIV related malignant lymphoma -Komagome Hospital- Dead Survived

16. Lung cancer -Komagome Hospital- Thirteen patients, all men Mean age59.0+-10.2 years Mean CD4 cell count332+-159 /μL HIV viral loadsUndetectable 8 patients HistologyAdeno 9, Squamous 3, Small 1 StageIA-IIIA 7, IIB/IV 6 Median survivalAll stage 17 month Advanced stage 14 month Int J Clin Oncol.2012;17:462-9

17. HPV related malignancy Cervical cancer Anal cancer HPV Ann Intern Med. 2008;148:728-736

18. Pathogenesis HIV Associated Cancers Oncology Reports. 2007;17: 1121-1126 :

19. Metabolic Complications and HIV

20. n=148n=228n=145 n=151 15.9% 32.5% 46.9% 58.3% （％） 20 Rate of HIV Patients with DM, HL and HT -Komagome hospital- DM: diabetes mellitus HL: hyperlipidemia HT: hypertension

21. Cardiovascular Disease ART Chronic inflam mation NNRTI vs. PI 1 ） - hyperlipidemia ABC ?/ ddI? 2 ） Treatment vs. observation 3 ） -damage of endothelial cell 1) NEJM. 2007;356: 1723-35. 2) Lancet. 2008; 371: 1417-26. 3) PLoS Med 2008; 5: e203

22. Chronic Kidney Disease ART CD4 HIV-RNA Other risks ART 1) TDF ＋ PIs 2) 1)AIDS. 2009; 23: 2143-9. 2) AIDS. 2009; 23: 1971-5. 3) AIDS. 2008; 22: 481-7. 4) AIDS. 2009; 23: 1219-26 Suppression of VL Increasing CD4 3) DM, hypertension HL, hepatitis C 4)

23. Prevalence of CKD - Komagome hospital- StageNo. of patientsComposition (%) Non-CKD16622.9 1324.4 243960.5 37610.5 450.69 530.41 5D50.69 Stage3-58912.2 GFR<60 ml/min/ 1.73m 2

24. Lifestyle Guidance Blood pressure Body weight Diet Exercise Smoking

25. Smoking Habit - Komagome Hospital-

26. Caregiving in People Living with HIV

27. Accelerated Aging in HIV Patients Chronic inflammation Chronic immune activation Immunosenescence

28. Demographic Trends in Japan -Declining birthrate and aging- -Growth of the nuclear family-

29. HIV Patient who Needs Caregiving -Komagome Hospital- Mr. B, 69-year-old man with HIV infection, chronic kidney disease and diabetes was diagnosed with cerebral infarction. Although he has severe consequence of gait and speech disturbance, he still wants to continue living daily life in his house. - What kind of service does he need ? - What kind of service can we offer ?

30. Collaboration in a Local Area Hospital Clinic Administrative organs Caregiving facilities Family Management of HIV infection Management of common diseases Professional caregiving Caregiving Management of welfare systems

31. Opportunistic infection Complications -Metabolic -Cardiovascular -Malignancies -Others HAART Caregiving - Impaired physical and mental function It is not easy to go up the mountain

32. Conclusion -New Challenges in the HAART era- Improvement of quality of life in HIV patients with - extended life expectancy - complications - impaired physical and cognitive function Sharing information on HIV infection in general population