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