Changing Epidemiology of Opportunistic Infections in the HAART

Era

International AIDS Society2012

Henry Masur MDChief, Critical Care Medicine Department

NIH-Clinical CenterBethesda, 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, 24:1549–1559

70

60

50

40

30

Inci

denc

e ra

te (p

er 1

000

PY)

CMV

PCP

Esophageal candidiasis

MAC

1999 2002 2003 20041994 2005 200720061995 1996 1997 1998 2000 2001

20

10

0

Year

Kaposi’s sarcoma

Non-Hodgkin’s lymphoma

Cervical cancerCNS

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

1999 2002 2003 20041994 2005 200720061995 1996 1997 1998 2000 2001

10

5

0

Year

Inci

denc

e ra

te (p

er 1

000

PY)

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 Prevalence

1996 – 2007

1999 2002 2003 20041994 2005 200720061995 1996 1997 1998 2000 2001

Year

Perc

ent a

mon

g H

IV h

ospi

taliz

atio

ns14

12

10

8

6

4

2

0

HOPS NHDS35

30

25

20

15

10

5

0

Pneumocystis Pneumonia

Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M

Inci

denc

e ra

te (p

er 1

000

PY)

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

1999133293

2002136766

2003153001

2004136772

2005124169

2006166111

1996185879

1997136075

1998148152

2000128631

2001137257

YearN =

Rat

e pe

r 100

,000

pop

ulat

ion 85

75

65

55

45

0

83.8

65.8

60.8

69.1

64.9

57.7

51.9

58.455.9

59.1 58.4

Kamimoto et al., National HIV Prevention Conference 2011, Atlanta GA, poster #085M

HIV Research Network: Length of Stay

MeanLOS (SD)in Days

MedianLOS (IQR)

in Days

Adjusted RelativeChange 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 DiagnosesNHDS, 1996 and 2006

1996 Diagnoses 2006 Diagnoses1. Thrush2. Anemia3. Volume depletion4. Pneumocystosis, PCP5. Pneumonia, unknown type6. Cytomegaloviral disease, CMV7. Wasting/cachexia8. Hyposmolality9. Aplastic anemia10.Convulsions

1. Thrush2. Pneumonia, unknown type3. Dehydration4. Hypertension5. Tobacco use disorder6. Acute renal failure7. Pneumocystosis8. Congestive heart failure9. Hepatitis C10.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): e12756. doi:10.1371/journal.pone.0012756

2007

AtlantaMetropolitan Area

Living with HIV 19,871New HIV Cases per 100,000 1,730Population Size 4.2*

HoustonMetropolitan Area

Living with HIV 19,534New HIV Cases per 100,000 1,360Population Size 4.4*

MiamiMetropolitan Area

Living with HIV 46,0307New HIV Cases per 100,000 3,500Population Size 4.5*

New YorkMetropolitan Area

Living with HIV 127,084New HIV Cases per 100,000 5,815Population Size 15.8*

PhiladelphiaMetropolitan Area

Living with HIV 25,098New HIV Cases per 100,000 1,750Population Size 4.8*

ChicagoMetropolitan Area

Living with HIV 26,222New HIV Cases per 100,000 1,768Population Size 7.7*

San FranciscoMetropolitan Area

Living with HIV 22,155New HIV Cases per 100,000 1,082Population Size 3.6*

BaltimoreMetropolitan Area

Living with HIV 17,251New HIV Cases per 100,000 1,423Population Size 2.2*

*Number in millions

Los Angeles Metropolitan Area

Living with HIV 41,650New HIV Cases per 100,000 2,700Population Size 10.4*

Washington DCMetropolitan Area

Living with HIV 27,992New HIV Cases per 100,000 2,652Metropolitan Population Size 4.4*DC Population Size 2.2*

Newly Diagnosed HIV Cases, District of Columbia, by Mode of Transmission, 2006-2010

0tan25a566525 0tan26a566526 0tan27a566527 0tan28a566528 0tan29a5665290tan28a566028

0tan10a566010

0tan21a566021

0tan3a56613

0tan14a566114

0tan25a566125

0tan7a56617

0tan19a566219

0tan1a56621

0tan13a566213

42.0%

43.2% 39.3%37.4% 39.7%

11.8%

9.8%9.1%

7.7%5.2%

2.1%

2.1%2.9%

1.6%1.9%

30.1%

32.0%

27.4%

32.0%33.5%

14.0%

12.9%

21.3%

21.4%19.6%

MSM IDU MSM/IDU Heterosexual contact RNI/Unknown

Num

ber o

f HIV

Cas

es

n=559

n=799n=769

n=575n=617

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

HIVn=845

Syphilis1.1%

Chlamydia3.3%

Gonorrhea2.1%

HCV7.3%

HBV3.7%

TB

Hepatitis C is a Common Public Health Problem in the U.S.

0

1

2

3

4

5

Population

Num

ber a

ffect

ed (m

illio

ns) HCV

HIV

Sulkowski MS, Clin Infect Dis. 2000;30:577-84.

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

Perc

enta

ge

IVDU90%

33%

HIV Coinfection Accelerates Liver Fibrosis Progression Rate

Fibr

osis

Gra

des

(MET

AVR

sco

ring

syst

em)

HIV positive (n=122)Matched controls (n=122)

HCV - infection duration (years)

4

3

2

1

0 0 10 20 30 40

Benhamou Y. Hepatology 1999;30:1054

Evolution of Chronic Hepatitis C Treatment

1989 1991 1992 1997 1998 1999 2001 2002

Discovery of HCV Protease

Inhibitors

2011

IFN-α2b+RBV

IFN-α2b

IFN-α2a

IFN-αcon IFN-αn1

PEG-IFN-α2b+RBV

PEG-IFN-α2a+RBV

Establishment of Hepatitis Clinics

Average Incidence Rateper 100,000 Population

0 - 25.025.1 – 50.050.1 – 75.075.1 – 100.0100.1 – 125.0

HCV/HIV

HCV

HIV/HBV

HBV

HIV/HCV/HBV

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