Acute HIV and the North Carolina STAT
Project
Index
• 20 yo white male
• July 29 Headache, fever
• Aug. 2 – Local ED
Underwent LP
Placed on Doxycycline … …possible Lyme
• Aug. 4th presented to another Local ED and admitted
Headache, fever, nausea, vomiting
labs: WBC 4.4; Plt 115;
RMSF Ab, TRUST, HIV ELISA Ab- neg.
Discharge Dx: Post- LP H/A
Possible viral ( aseptic) meningitis
Transmission
• Index symptoms resolve
• Aug.15th-30th
Index has sex with Partner A: 21 W male
They have unprotected sex 3-4x
Partner B : 22 W male joins for 3-way
• Aug.30-Sept.9th
Partner A&B have sex 1-2x/week
AHI Partners A&B
• Sept.10th
Partner A develops fever (104) x 7-10D
fatigue, sore throat
sees PMD given Z-pack and Vicodin
• Sept.30th
Partner B fever (101),sore throat,+/- rash
Sees PMD given Z-pack
Transmission
• Oct. 15th-20th
Partners A&B have three way Partner C
• Oct.28th – 30th
Partner C Sore Throat, oral ulcers, thrush, fever
• Oct.31st
Partner C visits LMD requests STI W/U ; antib./ no HIV test
• Nov.3rd
Partner C Dx Lymphoma and requests HIV test
• Nov. 15th
HIV ELISA + WB Indet.
Transmission
Index with AHI
Transmission to A
B
Transmission to C
C Dx AHI; And B come in for rapid testing on
World AIDS Day
Acute HIV
• The window period between:
- Appearance of HIV in blood
- Host Antibody response
• Seroconversion defined as “confirmed” by
+ WB
• Time period may narrow with newer
generation ELISAs
Couthino et al., Bulletin of Mathematical Biology 2001
Calculated transmission probabilities
based on semen HIV viral load at
peak (d23), set point (d120)
Rank
log spVL Prob/act Odds
Prob*/120d
75th %ile
5.58
.038
1:26
.126
50th %ile
4.79
.009
1:107
.032
25th %ile
3.88
.0018
1:556
.006
•Assumes 8 coital acts per month
Pilcher CD, et al., XIVth Int AIDS Conf, 2002
Transmission of HIV/coital act
Raki
Wawer et al, JID 2005
Diagnostic Testing Timeline
Symptoms
p24 Antigen
HIV RNA
HIV ELISA
0
1
2
3
4
5
6
7
8
9
10
Weeks Since Infection
Recombinant peptide ELISA
Viral lysate ELISA
Fiebig et al, AIDS
2003;17(13):1871-9
Two-Fold Benefit of Detecting AHI
1.
Individual Perspective
–
–
2.
Improve prognosis with acute treatment????
Entry into care and treatment
Public Health
–
–
Recognized previously missed infections
Avoid transmission to partners with risk reduction and ART
•
•
10-100 fold increased transmission risk x 5 months
May be responsible for ½ all transmission of HIV
- ID Transmission networks and geographic focus
transmission networks
partners at high risk
targeted interventions
identify high risk transmiitter
Pitfalls in AHI
• Diagnosis rarely pursued/rare event
• 30-40% of patients may be asymptomatic
• Signs and symptoms non-specific
– few clues
• Laboratory testing must be directed
The acute retroviral syndrome
• 49-89% symptomatic (Schacker TW, et al., AIM
1996 125:257-64)
• Symptoms
Fever
Fatigue
Pharyngitis
Weight loss
Myalgias
Headache 55
Schacker
93%
93
70
70
60
39
Kinloch-de Loes
87%
26
48
13
42
Primary (Acute) HIV:
PE abnormalities
•
•
•
•
•
•
•
Erythematous non-specific rash
Lymphadenopathy
Mucocutaneous ulcerations (oral/vaginal/esophageal)
Pharyngitis
Neurologic abnormalities (including encephalitis)
Oral manifestations
Serious OI’s rare
Laboratory abnormalities
•
•
•
•
•
Lymphocytopenia
Other -cytopenias
Atypical lymphocytosis rare early
Elevated transaminases
Lymphocytic pleocytosis and elevated
protein in CSF
Dx AHI
• How
• Considerations for which test
- sensitivity
-specificity
- positive and negative predictive value
- through put
- cost
Ways to reduce transmission
• Identify AHI
• Behavior change….. Abstain during hyperinfectious period (8 wks)
• HAART- to lower viral load ASAP
• Screen for STI
• Urgently trace partner network
Acute HIV and the North Carolina STAT
Project
North Carolina’s Perfect Storm
•
•
•
•
•
•
•
Named reporting
PCRS
Central Lab
Moderate prevalence
Integrated surveillance and field service
Integrated STD and HIV Branch
Close relationship UNC ID and UNC SPH
Our Approach to detection of AHI
• Screening of all HIV Ab negative or WB
indeterminate Blood from public clinics for
HIV RNA
• Review of all community cases
- Ab neg., HIV RNA +
- Ab.+ with Hx neg. HIV Ab within 3 mo
- Ab + but with recent acute symptoms
False Positive Rates Problem with
Individual Screening
• p24 Antigen
• HIV RNA PCR
0.2%
1-7%*
*False positives <10,000 copies/ml HIV RNA
How to make AHI Screening Possible:
Specimen pooling
• Advantages
Cost (Quinn, et al. AIDS 2000;14:2751-2757 )
Specificity
Improved positive predictive value
• Disadvantages
Requires large testing volume
Reduced sensitivity
Logistics
• STAT has provided proof of concept:
Screening for AHI IS feasible in a routine testing
population using ultrasensitive RT-PCR
Pooling and resolution testing
90 individual
specimens
9 intermediate
pools
(10 specimens)
1 master pool
(90 specimens)
A B C D E F G H I
A B C D E F G H I
1
2
3
4
5
6
7
8
9
10
A B C D E F G H I
A B C D E F G H I
Clinical Reporting (2)
+
EIA/WB
Long Term HIV Positive
NAAT
-
+
F/U Testing
(Ab+NAAT)
HIV Negative
+
Acute HIV
Nov. 02- March 23 2006
Yr 1
Yr 2
Yr 3
Yr4
# True +
69
22
20
21
6
# False
RNA +
# False
EIA neg.
#Comm.
5
2
2
1
0
2
1
1
0
0
80
11
23
21
25
2/3 of AHI cases Dx from STD clinics 2002-2003
Antibody-negative HIV Infections
as a Proportion of All Detected Cases
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
1%
6%
6%
6%
4%
The Future
• Expand AHI screening in ERs, Urgent Care, and
inpatient settings
• Remove barriers for HIV testing in the above
settings
• Remove need for written informed consent
( not required by law)
• Remove requirement for pre-test counseling
• Limit post-test requirement to positives only
• Develop predictive models for AHI screening and
testing
Who is joining the party
•
•
•
•
•
•
•
•
Colorado
Baltimore STD clinics
FLA demonstration project
LA STD clinics
New York City
New York State – Rochester
San Francisco STD clinics
Seattle MSM and SEP
NC STD clinics and AHI
• Entry point for high risk individuals
• Overlap of incubation periods of classic
STIs and HIV
• Already drawing blood for syphilis
• Opt out approach for HIV testing
• Integration of HIV and STD programs
Rapid Testing “Plus”:
Specimens
• Fingerstick or oral fluid testing makes effective
HIV antibody testing possible in non-traditional
settings
– most HIV testing is in traditional settings
• Venous blood is routinely obtained for diagnostic
tests at most HIV testing sites (STD clinics,
prenatal clinics, SEP activities, etc)
– Patients prefer non-venipuncture rapid tests…but
“preference” does not mean mutually exclusive choices
nor does it justify missing AHI
Conclusions
• Continued exclusive use of HIV antibody tests
will miss 4-10% of truly HIV+ individuals, at the
precise moment of their maximum transmission
potential
• With emergent results notification and PCRS,
acute HIV screening is direct HIV prevention
• STAT has immediate impact on vertical HIV
transmission
• STAT is cost effective
• Acute screening can be used to “back up” rapid
tests
HCV Risk Factors
Parenteral
Sexual
Perinatal
IVDU
Nasal cocaine
Transfusions
Transplant
Occupational exposure
Tattoos/Body piercing
Manicures
Household items
Multiple partners
Traumatic
HIV (+)
High viral load
HIV (+)
Toothbrush, razor
HIV (+), positive for human immunodeficiency virus; IVDU, intravenous drug use.
NIH Consensus Development Conference Statement. June 10-12, 2002;
Bethesda, Md.
SEXUAL TRANSMISSION:
RECOMMENDATIONS
• Inform HCV carriers of risks
• Test partner for HCV
• No modification of long-standing monogamous
relationships
• Safer sex for promiscuous behavior
• Some concern that genital ulcerative diseases
( LGV,HSV) may facilitate HCV tranmsission.
Factors Associated With
Disease Progression
• Alcohol consumption
– 30 g/day in men
– 20 g/day in women
•
•
•
•
Disease acquisition at >40 years
Male
HIV coinfection
Hepatitis B virus coinfection
NIH Consensus Development Conference Statement. June 10-12, 2002;
Bethesda, Md.
Poynard et al. Lancet. 1997;349:825-832.
The co-infection dilemma
• High co-infection rate of HCV in HIV infected
• Few dually infected receive HCV therapy
•
•
•
•
•
•
Why?
Administration of therapy
Historically poor response rates
Coverage of therapy cost
Dual and triple diagnosis
Liver Bx
Lack of experienced care providers
What to do
• Raise awareness of the HCV epidemic
• Cross train HIV providers in HCV management
• Provide free screening for at risk populations
- currently only 1 health department offers
free HCV screening
• Surveillance – both chronic and acute HCV
- develop acute HCV screening
( variation of pooling mech.)
- increase free screening
• Expand coverage for HCV therapy
• Vaccinate at risk populations for HAV and HBV
• GET PROVIDERS to TREAT!
What to do is not solely
dependent on therapy
• Vaccinate for HAV and HBV
• Council on reducing ETOH
• Risk reduction for transmission