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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
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Changing Epidemiology of Opportunistic Infections in the HAART EraInternational AIDS Society2012 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, 1994–2007High-Frequency Opportunistic Infections 70 CMV 60 Incidence rate (per 1000 PY) 50 40 PCP 30 MAC 20 Esophageal candidiasis 10 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year Buchacz K et al. AIDS 2010, 24:1549–1559
Incidence of AIDS-Defining Opportunistic Illnesses HIV Outpatient Study, 1994–2007 Opportunistic Malignancies 35 30 Incidence rate (per 1000 PY) Kaposi’s sarcoma 25 20 15 Non-Hodgkin’s lymphoma 10 Cervical cancer CNS lymphoma 5 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year Buchacz K et al. AIDS 2010, 24:1549–1559
Life Expectancy: NA-Accordn=65,584 with 8105 Deaths, 1996-2006 • Life expectancy at age 20 increased • +27 years (1996-9) vs. +52 years (2006-7) • Men and women comparable • men (+55 yrs) = women (+46 yrs) • Other differences in life expectancy (2006-7) • IDU (+43) < MSM (+59) • AA (+51) <white (+56) or Latino (+61) • CD4 <100 (+19) < 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. • 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
Selected HIV–Associated ConditionsHOPS Cohort Incidence and NHDS Prevalence1996 – 2007 Pneumocystis Pneumonia HOPS NHDS Percent among HIV hospitalizations 35 14 Incidence rate (per 1000 PY) 30 12 25 10 20 8 15 6 10 4 5 2 0 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M
Rates of Select OIs: HOPS Incidence and NHDS Prevalence, 1996-2007 Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M
HIV–Associated Hospitalization RatesNHD, 1996 – 2006 85 Rate per 100,000 population 83.8 75 69.1 65 65.8 64.9 60.8 59.1 55 58.4 58.4 57.7 55.9 51.9 45 0 Year N = 1996 185879 1997 136075 1998 148152 1999 133293 2000 128631 2001 137257 2002 136766 2003 153001 2004 136772 2005 124169 2006 166111 Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M
HIV Research Network: Length of Stay Berry SA et al. J Acquir Immune DeficSyndr 2012;59:368–375)
Leading HIV-Associated Hospital DiagnosesNHDS, 1996 and 2006 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 2007 Hall HI et al. PLoS ONE 5(9): e12756. doi:10.1371/journal.pone.0012756 *Number in millions
Newly Diagnosed HIV Cases, District of Columbia, by Mode of Transmission, 2006-2010 n=799 n=769 n=617 n=575 n=559
Continuum of Care for HIV Cases Diagnosed in the District of Columbia, 2005-2009
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. 5 HCV 4 3 Number affected (millions) 2 1 HIV 0 Population Sulkowski MS, Clin Infect Dis. 2000;30:577-84.
HCV Coinfection is Very Common in HIV Infected Subjects IVDU 100 90% 80 60 Percentage All HIV+ 40 33% 20 0 Population Sulkowski MS, Clin Infect Dis. 2000;30:577-84.
HIV Coinfection Accelerates Liver Fibrosis Progression Rate 4 3 Fibrosis Grades (METAVR scoring system) 2 HIV positive (n=122) Matched controls (n=122) 1 0 30 10 20 40 0 HCV - infection duration (years) Benhamou Y. Hepatology 1999;30:1054
Evolution of Chronic Hepatitis C Treatment Discovery of HCV Protease Inhibitors PEG-IFN-α2b+RBV IFN-α2b+RBV IFN-α2a PEG-IFN-α2a+RBV IFN-αcon IFN-αn1 IFN-α2b 1989 1991 1992 1997 1998 1999 2001 2002 2011
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
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