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

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

Incidence of AIDS-Defining Opportunistic Illnesses HIV Outpatient Study, 1994–2007 High-Frequency Opportunistic Infections Buchacz K et al. AIDS 2010, 24:1549– Incidence rate (per 1000 PY) CMV PCP Esophageal candidiasis MAC Year

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– Year Incidence rate (per 1000 PY)

Life Expectancy: NA-Accord n=65,584 with 8105 Deaths, 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

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

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, Weighted to provide national estimate of hospitalizations Weighted to provide national estimate of hospitalizations

Selected HIV–Associated Conditions HOPS Cohort Incidence and NHDS Prevalence 1996 – Year Percent among HIV hospitalizations HOPSNHDS Pneumocystis Pneumonia Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M Incidence rate (per 1000 PY)

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

HIV–Associated Hospitalization Rates NHD, 1996 – Year N = Rate per 100,000 population Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M

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)

Leading HIV-Associated Hospital Diagnoses NHDS, 1996 and 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

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

50% of People with HIV in the United States Reside in 12 Cities Hall HI et al. PLoS ONE 5(9): e doi: /journal.pone 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*

Newly Diagnosed HIV Cases, District of Columbia, by Mode of Transmission, n=559 n=799 n=769 n=575 n=617

Continuum of Care for HIV Cases Diagnosed in the District of Columbia,

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

Hepatitis C is a Common Public Health Problem in the U.S Population Number affected (millions) HCV HIV Sulkowski MS, Clin Infect Dis. 2000;30:

HCV Coinfection is Very Common in HIV Infected Subjects Population Sulkowski MS, Clin Infect Dis. 2000;30: All HIV Percentage IVDU 90% 33%

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

Evolution of Chronic Hepatitis C Treatment 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

Establishment of Hepatitis Clinics Average Incidence Rate per 100,000 Population – – – – 125.0

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

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