Acute HIV in North Carolina STD Clinics
The North Carolina STAT Project
Peter A. Leone, MD
Associate Professor of Medicine
University of North Carolina
Medical Director,
NC HIV/STD Prevention and Care, NCDHHS
Acute HIV
• The window period between:
- Appearance of HIV in blood
- Host Antibody response
• Seroconversion defined as “confirmed” by
+ WB
• Time period (4-8 weeks) may narrow with
newer generation ELISAs
Couthino et al., Bulletin of Mathematical Biology 2001
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
Rationale for Acute HIV Diagnosis
• Most Infectious period and Dx often missed
• Individual Perspective
– Improve prognosis with acute treatment????
– Early entry into care
• Public Health
– Recognized previously missed infections
– Avoid transmission to partners with risk reduction
• 10-100 fold increased transmission risk x 4-6 months
• May be responsible for 30-50% of all transmission of HIV
- Identify Transmission networks for intervention
Pitfalls in AHI
• Diagnosis rarely pursued/rare event
• Majority of patients may be asymptomatic
• Signs and symptoms non-specific
– few clues
• Laboratory testing must be directed
• Linkage to surveillance and PCRS in real
time
Kahn JO, Walker BD, N Engl J Med1998;339: 33-39.
The North Carolina STAT Project
NC Approach to detection of AHI
• Screening of all HIV Ab negative or WB
indeterminate Blood from public clinics for
HIV RNA ( ~120,000 tests/year)
• Review of all community cases
- Ab neg., HIV RNA +
- Ab.+ with Hx neg. HIV Ab within 3 mo
- Ab + but with recent acute symptoms
Our approach to Screening for AHI
Specimen pooling
• Advantages
Reduced cost
No change in specificity
Universal screening
• Disadvantages
Requires large testing volume
Trade off in sensitivity
Logistics
Time to locating patient
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
NC STAT
All Testing Sites
Nov.1, 2002- May 1,2005
• Number screened: 287,760
• Number of Ab+:
1,379
• Number of AHI:
58
• AHI represents ~4.0% of all HIV infected
Testing Site Type
#Tests
Ab+ AHI (%)
18,299
117,804
47,476
47,598
7,158
37,073
400
526
28
39
57
320
Distribution of
Total AHI
(%)
HIV CTS
STD
FP
Prenatal/OB
Prison/Jail
Other
12 (2.9)
27 (4.9)
-2 (4.9)
4 (6.6)
13(3.9)
21%
48%
-3%
7%
22%
Demographic Comparisons
Factor
Sex
Male
Female
Age (years)
Race
White, non-Hispanic
Black, non-Hispanic
Hispanic
Asian/Pacific Islander
Am Indian/AK Native
Other
Undetermined
AHI in STD Clinics
(n=27)
Testing population
(n=287,760 )
HIV+ population*
(n=1,377)
No.
%
No.
%
No.
%
19
8
70.4
29.6
95,593
188,391
33.7
66.3
930
427
68.5
31.5
Median: 25
(Range:18-52)
3
21
2
0
1
0
0
11.1
77.8
7.4
0
3.7
0
0
P<0.001
P=0.84
Median: 25
(Range:0-99)
Median: 33
(Range:0-68)
103,809
129,378
45,709
2,052
2,802
1,571
80
36.4
45.3
16.0
0.7
1.0
0.6
0.03
245
974
123
4
11
8
1
17.9
71.3
9.0
0.3
0.8
0.6
0.07
NC STD Clinic AHI
Reason for Visit
• STD related visit
Yes 22% (6)
No 78% (21)
• STD Dx
Yes 44% (12) *
No
56% (15)
* 6/12 STD with GC
AHI and Symptoms
• 49-89% symptomatic (Schacker TW, et al.,
AIM 1996 125:257-64)
• Symptoms
Fever
Fatigue
Pharyngitis
Headache
Rash
GI Symptoms
Schacker
93%
93
70
55
Kinloch-de Loes
87%
26
48
39
NCSTD
48%
37
30
26
15
37
AHI with Retroviral Symptoms
STD Sites
Factor
Total (N=27)
Any symptoms at any time
No.
20
%
74%
Any symptoms at testing
11
40.7
Any symptoms after testing
11
40.7
STD or symptoms at testing
21
77.8
Specific Symptoms at Time of
Testing in STD Clinics
Symptoms
Total (%)
Fever
Fatigue
GI Symptoms
Pharyngitis
Headache
Rash
Lymphadenopathy
6 (22%)
5 (18)
5 (18)
3 (11)
3 (11)
1 (4)
1(4)
Why Pursue AHI
in STD Clinic Populations
• Entry point for high risk individuals
• High % of AHI in public health setting
• Overlap of incubation periods of classic
STIs and HIV
• Already drawing blood for syphilis
• Opt out approach for HIV testing
Incorporating AHI Screening in STD
clinics:
1.
Screen all
2.
Rapid Test “Plus”
-Rapid HIV tests can be offered with symptom screen
Problem: Which symptoms (fever?) over what time period (2-4 wks)?
Symptoms at best will detect 40%
- Targeted screening
based on risk ( i.e. MSM, anal/vaginal sex in past 2 weeks,etc )
based on site prevalence or type
3. Bottom line- rapid testing and AHI screening are not mutually exclusive
-Need for further research to define symptom screen and develop predictive
models for AHI screening
Women with AHI
Case
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Age
36
34
44
29
35
41
21
48
16
28
25
18
21
22
41
32
Race
Black
Amind
Black
White
Black
Black
Black
Hispanic
Black
Black
Black
Black
Black
Hispanic
White
Black
Testing Site
Nontraditional
STD Clinic
STD Clinic
Prison
STD Clinic
STD Clinic
STD Clinic
Nontraditional
Prenatal/OB
STD Clinic
HIV CTS
STD Clinic
STD Clinic
Prenatal/OB
Other
HIV CTS
Risk Factor
Injection Drug Use
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Heterosexual
Injection Drug Use
Heterosexual
5/16 AHI women were pregnant at the time of testing. All were initiated on ART, received AZT at
delivery, as did their infants. None of the infants were infected.
During this same frame, there were 6 HIV+ infants born in NC. 3/6 infants were born to
women who retrospectively were found to have seroconverted after having undergone
routine HIV testing earlier in pregnancy. This supports the use of a repeat testing strategy in
pregnant women.
Pregnancy Conclusion
• STAT was effective in identifying 5 AHI pregnant women, resulting in
prompt initiation of ART and, ultimately, preventing transmission of
HIV to these at risk infants.
• Three of the 6 women who delivered HIV-infected infants during this
same period seroconverted after undergoing HIV testing early in
pregnancy. The strategy of AHI screening or repeat HIV testing is most
likely highly cost effective due to the high risk and rate of vertical
transmission in acutely infected pregnant women. A formal cost
effectiveness analysis is in progress.
• Despite our overall low numbers of perinatal transmission, NC’s
universal enhanced screening strategy has had an impact on the
residual transmission of MTCT in our state.
Recommendations
• The residual cases of perinatal transmission may be reduced further if
the following strategy were to be implemented domestically:
• Universal HIV testing of all pregnant women early in pregnancy. For
all Ab(-) women, reflex testing with HIV RNA.
• For women who do have reflex RNA testing and are negative, repeat
HIV Ab testing in the third trimester.
• All women who were Ab(-) RNA (-) early in pregnancy and did not
have repeat testing in the third trimester, rapid testing with reflex HIV
RNA at the time of delivery should be performed.
• All Ab(+) or Ab(-)RNA(+) pregnant women should be initiated on
ART as soon as possible.
Acknowledgements
NC DHHS
Evelyn Foust
J. Todd McPherson
Lou Turner
Leslie Wolf
Todd Vanhoy
Rhonda Ashby
Del Williams
Steve Beagle
UNC-Chapel Hill
Christopher Pilcher
Susan A. Fiscus
Joseph J. Eron, Jr
JoAnn Kuruc
Myron S. Cohen
Kris Patterson
William C. Miller
Trang Q. Nguyen
Sandi McCoy
North Carolina DIS
NIMH , NIDDK, HPTN, UNC Fogarty Center, UNC STD
CRC, UNC CFAR