Transcript Acute HIV Infection: New Frontiers for HIV Prevention

Acute HIV Infection: New
Frontiers for HIV Prevention
Antonio E. Urbina, MD
Medical Director HIV Education and Training
St. Vincent Catholic Medical Center-Manhattan
May 17, 2006
St. Vincent Catholic Medical Center is a
Local Performance Site of the NY/NJ AETC
Lifetime Cost of HIV Care in the
US in the Current Treatment Era
$500,000
B R Schackman, et al Abstract, 3rd IAS Conference
HIV Incidence
Since 1999, HIV infections have
remained steady at 40-45,000/year
CDC HIV/AIDS Surveillance Report
12% of US
population
CDC HIV/AIDS Surveillance Report 2003
Prevention vs. Treatment
• Structure of US health system favors
treatment over prevention
• Access to healthcare is tied to labor market
and not citizenship
• Our for-profit health system favors
treatment over prevention
– More profits are generated when people are ill
as opposed to when they are well
Improve HIV Detection
• Normalize HIV Testing
– outpatient and inpatient settings
• Increase detection of persons in acute HIV
infection (AHI)
• Use pooled plasma viral load testing
(PPLVT) in high risk settings, i.e. STD
clinics
Leone P UNC
Primary HIV-1 Infection
Acute + Recent (4-6 months)
1000
800
+
CD4
Cells
600
Early Opportunistic Infections
Late Opportunistic Infections
400
200
0
1
Infection
2
3
4
5
6
7
8
9
10 11 12 13 14
Time in Years
Leone P UNC
Days from sexual exposure to onset of symptoms in 12 patients who could
identify the exact date and time of the sexual exposure that led to acquisition of
human immunodeficiency virus
Schacker, T. et. al. Ann Intern Med 1996;125:257-264
Detection of HIV by Diagnostic
Tests
Symptoms
p24 Antigen
HIV RNA
HIV EIA*
Western blot
0
1
After Fiebig et al, AIDS 2003;
17(13):1871-9
2
3
4
5
6 7
8
Weeks Since Infection
9
*3rd generation, IgM-sensitive EIA
*2nd generation EIA
*viral lysate EIA
10
Acute HIV Infection
(www.hivguidelines.org)
How effective are we at capturing
AHI?
Acute HIV Infection (AHI)
• Nearly 60 million individuals diagnosed
with HIV, fewer than 1,000 cases have been
diagnosed in AHI [1]
– 1/60,000 detection rate
• In NYC, fewer than 20 cases of AHI have
been diagnosed [2]
[1] Pilcher, et al AIDS 2004
[2] NYC DOH STARHS Program
Why so lax in diagnosing AHI?
• 1. Treatment and diagnosis of HIV
infection has been relegated to specialists
– Lack of education of how to diagnose AHI
– Discomfort related to difficult issues
surrounding HIV
• 2. Clinicians inability to spend the
additional time
Flanigan T, et al Annals of Int Med 2001
AHI
• 1% of patients with negative tests for EBV
had AHI [1]
• 1% of patients with “any viral syndrome” in
a Boston urgent care center had AHI [2]
• In a Malawi STD clinic, 2.8% of all male
clients with acute STD had AHI [3]
[1] Rosenberg, et al N Engl J Med 1999
[2] Pincus, et al Clin Infect Dis 2003
[3] Pilcher, et al AIDS 2004
Clinical Presentation of HIV Seroconversion*
Schacker, T. et. al. Ann Intern Med 1996;125:257-264
How do you diagnose?
ICD-9 Code for AHI
(exposure to HIV)
VO1.7
AHI and Hyperinfectiousness
• Growing evidence that persons in AHI are
very infectious
– High-titer viremia in plasma and genital fluids
[1,2]
– Absence of immune factors that may neutralize
infectivity [2]
Kahn JO, et al N Engl J Med 1998
Quinn TC, et al N Engl J Med 2000
AHI and Sexual Risk Behavior
MSM seroconverters from HIVNet Vaccine Trial
Colfax, G et al AIDS 2002
Role of AHI in Secondary
Transmissions
• Koopman [1] and Jacquez [2] used population
modeling to argue that the spread of HIV
from patients in AHI could contribute
disproportionately to the epidemic
– suggested that patients in AHI could be up to
1,000 x more infectious than those in chronic
infection
Koopman JS, et al J Acquir Immune Defic Synd Hum Retrovirol 1997
Jacquez JA, et al J Acquir Immune Defic Syndr 1994
Blood viral load in acute HIV (n=171)
log 10 HIV RNA
Average fitted curve, with 95% confidence intervals
8
7
6
5
4
3
2
1
0
8-10 fold increase risk from peak to day 54
0
100
200
300
Days from Infection
Peak: day 23
Pilcher, et al JID 2004
Semen viral load in acute HIV (n=30)
log 10 HIV RNA
7
6
5
4
3
2
1
0
0
10 20 30 40 50 60 70 80 90 100
Days from Infection
Pilcher, et al JID 2004
Rates of HIV-1 Transmission per Coital Act, by
Stage of HIV-1 Infection, in Rakai, Uganda
• Retrospectively identified 235 monogamous, HIVdiscordant couples in Ugandan population-based
cohort from 1994-1999
• Estimated rates of HIV transmission per coital act
in HIV discordant couples by stage of infection in
the index partner
– Recent seroconversion vs. chronic vs. late stage
– HIV transmission within pairs was confirmed by
sequence analysis
Wawer, et al JID, 2005
Wawer, et al JID, 2005
Transmission Of HIV During AHI:
Relationship To Sexual Risk And STI
• 103 individuals with AHI were followed from
1999-2003
• Viruses from 34% were related
• Significant associations with clustering were:
–
–
–
–
–
Young age
High CD4 count
Number of sexual partners
UAI
STIs
Pao P et al AIDS 2005
Clustering: efficient dissemination by
core groups and identification of
networks
“Efficient
disseminator”
Identification of
network
Identification via
PHI
“Acute Case”
Why isn’t individual viral load testing
incorporated into HIV Testing?
• Direct HIV detection methods (RNA testing) are
expensive—5 to10 x more than Ab tests
– Cost range from $60-$290
• Decreased specificity
– False positives
– Typically viral loads <5000 are FP
• Pooling specimens improves specificity and greatly
reduces cost
Pooling schema
Individual
specimens
Pools of 10
Pooling schema
A B C D EF G H I J K
Individual
specimens
N=100
Pools of 10
A B C D E F G H I J K
Pooling schema
A B C D EF G H I J K
Individual
specimens
N=100
Pools of 10
A B C D E F G H I J K
Master pool
Resolution Testing
A
Individual
testing on 10
specimens
Pools of 10
screened
Master pools
screened
A B C D E
Detection of AHI during HIV Testing in
North Carolina
• 12 month observational study to evaluate
this strategy for HIV testing at 110 publicly
funded sites in NC
• Primary objective was to compare the
performance and yield of standard AB
testing with algorithm that included both
standard AB testing and PPVLT
Pilcher, et al NEngl J Med 2005
Performance of Algorithm
• Sensitivity for standard AB testing (sAb)
was 0.962
• Use of PPLVT increased rate of HIV case
identification by 3.9% over that sAB
• Specificity and positive predictive value
(PPV) of combined testing (Ab + PPVLT)
with pooling was 0.999 and 0.997
6%
in
AHI
Interventions Targeting Acute
Infection
• All subjects (n=23) with AHI were notified
(within 72 hours after test results)
– No adverse events were reported (e.g.,
psychological trauma, violence against or from
partners, etc)
– 21/23 subjects with AHI began specialty
medical care, including 1 pregnant woman who
received ARVS (baby was negative)
Pilcher, et al NEngl J Med 2005
Interventions Targeting Acute
Infection
• 48 sexual partners of subjects with AHI received
counseling for risk reduction
– 18 of these (38%) had HIV infection
• 13 (27%) previously recognized
• 5 (10 %) newly diagnosed
• 11 were probably the source of the AHI
– 10 were aware of their status, but only 3 disclosed to
partners
– 3 of possible transmitters had been named in
surveillance records as potential source of infection in 3
other cases suggesting roles as “core transmitters”
Pilcher, et al NEngl J Med 2005
Social Networks and Risk
Association
• Designated case managers collected data on
social networks of acutely infected subjects
• 4 were college students; 2 in one town were
identified within 1 month of each other
– Revealed a new HIV outbreak among young
black MSMs in these colleges
Pilcher, et al NEngl J Med 2005
Costs
• PPLVT added an additional $3.63 per
specimen and $17,515 per additional index
case identified
• Added only 3.3% increase over annual
budget
Pilcher, et al NEngl J Med 2005
Thanks
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•
•
•
Frederick Siegal, MD
Barbara Johnston, MD
Paul Galatowitsch, PhD
All staff at the HIV Center