1. Changing Epidemiology of Opportunistic Infections in the HAART Era International AIDS Society 2012 Henry Masur MD Chief, Critical Care Medicine Department NIH-Clinical Center Bethesda, Maryland

2. Determinants of Opportunistic Infections Exposure – – Geographic variability – – Occupational/non occupational factors Degree of immunosuppression – – Early vs late detection – – Effectiveness of ART HIV viral load Prophylaxis – – Immunizations – – Chemotherapy

3. Incidence of AIDS-Defining Opportunistic Illnesses HIV Outpatient Study, 1994–2007 High-Frequency Opportunistic Infections Buchacz K et al. AIDS 2010, 24:1549–1559 70 60 50 40 30 Incidence rate (per 1000 PY) CMV PCP Esophageal candidiasis MAC 19992002200320041994200520072006199519961997199820002001 20 10 0 Year

4. Kaposi’s sarcoma Non- Hodgkin’s lymphoma Cervical cancer CNS lymphoma Incidence of AIDS-Defining Opportunistic Illnesses HIV Outpatient Study, 1994–2007 Opportunistic Malignancies Buchacz K et al. AIDS 2010, 24:1549–1559 35 30 25 20 15 19992002200320041994200520072006199519961997199820002001 10 5 0 Year Incidence rate (per 1000 PY)

5. Life Expectancy: NA-Accord n=65,584 with 8105 Deaths, 1996-2006 Life expectancy at age 20 increased Life expectancy at age 20 increased – +27 years (1996-9) vs. +52 years (2006-7) Men and women comparable Men and women comparable – men (+55 yrs) = women (+46 yrs) Other differences in life expectancy (2006-7) Other differences in life expectancy (2006-7) – IDU (+43) < MSM (+59) – AA (+51) <white (+56) or Latino (+61) – CD4 350 (+42) Hogg CROI 2012 #137

6. Status of Opportunistic Infections in United States Two populations – – Access/adherence to early detection and ART – – Poor access resulting in late detection/poor adherence

7. National Hospital Discharge Survey (NHDS) Conducted annually by the National Center for Health Statistics, CDC. Conducted annually by the National Center for Health Statistics, CDC. Three-stage sample of non-Federal, short-stay hospitals in the 50 states Three-stage sample of non-Federal, short-stay hospitals in the 50 states – On average, 451 hospitals participated each year, 1996-2006 Weighted to provide national estimate of hospitalizations Weighted to provide national estimate of hospitalizations

8. Selected HIV–Associated Conditions HOPS Cohort Incidence and NHDS Prevalence 1996 – 2007 19992002200320041994200520072006199519961997199820002001 Year Percent among HIV hospitalizations 1412 10 8 6 4 2 0 HOPSNHDS35 30 25 20 15 10 5 0 Pneumocystis Pneumonia Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M Incidence rate (per 1000 PY)

9. Rates of Select OIs: HOPS Incidence and NHDS Prevalence, 1996-2007 Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M

10. HIV–Associated Hospitalization Rates NHD, 1996 – 2006 19991332932002136766200315300120041367722005124169200616611119961858791997136075199814815220001286312001137257Year N = Rate per 100,000 population 85 75 65 55 45 0 83.8 65.8 60.8 69.1 64.9 57.7 51.9 58.4 55.9 59.1 58.4 Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M

11. HIV Research Network: Length of Stay Mean LOS (SD) in Days Median LOS (IQR) in Days Adjusted Relative Change in LOS vs. ADI Category (95% CI) AIDS-Defining 10.5 (10.6) 7 (5–12) 1.00 (ref) Non–AIDS- Cancer 7.7 (8.3) 5 (3–8) 0.81 (0.71, 0.92) Non–AIDS-Infection 7.3 (7.7) 5 (4–8) 0.74 (0.69, 0.80) All Cause 7.2 (8.1) 5 (3–8) Not compared Berry SA et al. J Acquir Immune Defic Syndr 2012;59:368–375)

12. Leading HIV-Associated Hospital Diagnoses NHDS, 1996 and 2006 1996 Diagnoses 2006 Diagnoses 1.Thrush 2.Anemia 3.Volume depletion 4.Pneumocystosis, PCP 5.Pneumonia, unknown type 6.Cytomegaloviral disease, CMV 7.Wasting/cachexia 8.Hyposmolality 9.Aplastic anemia 10.Convulsions 1.Thrush 2.Pneumonia, unknown type 3.Dehydration 4.Hypertension 5.Tobacco use disorder 6.Acute renal failure 7.Pneumocystosis 8.Congestive heart failure 9.Hepatitis C 10.End stage renal disease Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M

13. Early Morbidity/Mortality after ART Initiation 40% US Patients Diagnosed with CD4<200 Considerable Morbidity Immediately Post ART New opportunistic diseases Medication toxicities Non-infectious IRIS Months

14. 50% of People with HIV in the United States Reside in 12 Cities Hall HI et al. PLoS ONE 5(9): e12756. doi:10.1371/journal.pone.0012756 2007 Atlanta Metropolitan Area Living with HIV 19,871 New HIV Cases per 100,000 1,730 Population Size 4.2*Houston Metropolitan Area Living with HIV 19,534 New HIV Cases per 100,000 1,360 Population Size 4.4*Miami Metropolitan Area Living with HIV 46,0307 New HIV Cases per 100,000 3,500 Population Size 4.5* New York Metropolitan Area Living with HIV 127,084 New HIV Cases per 100,000 5,815 Population Size 15.8* Philadelphia Metropolitan Area Living with HIV 25,098 New HIV Cases per 100,000 1,750 Population Size 4.8* Chicago Metropolitan Area Living with HIV 26,222 New HIV Cases per 100,000 1,768 Population Size 7.7* San Francisco Metropolitan Area Living with HIV 22,155 New HIV Cases per 100,000 1,082 Population Size 3.6* Baltimore Metropolitan Area Living with HIV 17,251 New HIV Cases per 100,000 1,423 Population Size 2.2* *Number in millions Los Angeles Metropolitan Area Living with HIV 41,650 New HIV Cases per 100,000 2,700 Population Size 10.4* Washington DC Metropolitan Area Living with HIV 27,992 New HIV Cases per 100,000 2,652 Metropolitan Population Size 4.4* DC Population Size 2.2*

15. Newly Diagnosed HIV Cases, District of Columbia, by Mode of Transmission, 2006-2010 n=559 n=799 n=769 n=575 n=617

16. Continuum of Care for HIV Cases Diagnosed in the District of Columbia, 2005-2009

17. Proportion of HIV Cases Diagnosed with a Co-infection, District of Columbia, 2010

18. Hepatitis C is a Common Public Health Problem in the U.S. 0 1 2 3 4 5 Population Number affected (millions) HCV HIV Sulkowski MS, Clin Infect Dis. 2000;30:577-84.

19. HCV Coinfection is Very Common in HIV Infected Subjects Population Sulkowski MS, Clin Infect Dis. 2000;30:577-84. All HIV+ 0 20 40 60 80 100 Percentage IVDU 90% 33%

20. HIV Coinfection Accelerates Liver Fibrosis Progression Rate Fibrosis Grades (METAVR scoring system) HIV positive (n=122) Matched controls (n=122) HCV - infection duration (years) 4 3 2 1 0 0 1020 30 40 Benhamou Y. Hepatology 1999;30:1054

21. Evolution of Chronic Hepatitis C Treatment 19891991199219971998199920012002 Discovery of HCV Protease Inhibitors 2011 IFN- α 2b +RBV IFN-α2b IFN- α 2a IFN- α con IFN- α n1 PEG-IFN- α 2b +RBV PEG-IFN- α 2a +RBV

22. Establishment of Hepatitis Clinics Average Incidence Rate per 100,000 Population 0 - 25.0 25.1 – 50.0 50.1 – 75.0 75.1 – 100.0 100.1 – 125.0

23. Create An Urban Model for Reducing Impact of HIV Create Urban Model for Reducing Impact of HCV

24. Challenges for Opportunistic Infections 2012-US Opportunistic Infections are still common – – Late detection in regions, especially urban – – Occurrence pre-ART and post ART – – TB continues to be uncommon but... Expertise in management may be waning Early initiation of ART is the best preventive intervention – – US cities have far to go New challenges for well controlled patients – – HCV, HPV, and accelerated inflammation – – New generation of therapies esp for HCV