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Acute HIV and the North Carolina STAT Project

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Title: Acute HIV and the North Carolina STAT Project


1
Acute HIV and the North Carolina STAT Project
  • Past, Present and Future
  • Peter Leone, MD
  • Associate Professor of Medicine
  • University of North Carolina
  • Medical Director
  • North Carolina HIV/STD Prevention and Care

2
9/10/05 Develops fever, ST, fatigue Local PMD
gives Z-pack
8/15/05-8/30/05 AB Sex 3-4x
10/28/05 Develops fever, ST, oral ulcers,
thrush Antibiotics given Requests HIV test
Partners BC steady Sex 1-2x/wk
8/30/05 A,B,C 3-way
7/28/05 Develops HA, Fever Went to ER, LP,
labs DX RMSF, doxycycline given Symptoms worsen
2 Days later admitted HIV Ab neg Discharge
Aseptic meningitis Possible RMSF
10/15/05 B,C,D have 3-way
9/30/05 Develops fever, LAD,ST Local PMD gives
Z-pack
3
D
11/15/05 HIV (ELISA WB I)
4
12/1/05 HIV
B
11/15/05 HIV (ELISA WB I)
D
C
12/1/05 HIV
5
12/1/05 HIV
B
11/15/05 HIV (ELISA WB I)
D
A
12/20/05 HIV
C
12/1/05 HIV
6
12/1/05 HIV
B
11/15/05 HIV (ELISA WB I)
D
A
12/20/05 HIV
C
12/1/05 HIV
5 infections could have been avoided if acute HIV
infection considered at first presentation
7
Definition of Acute HIV Infection
  • Time period following infection with HIV during
    which HIV virus can be detected in blood but
    antibodies to HIV are not
  • OR
  • Window period when routine HIV antibody tests
    (EIAs) are negative but HIV virus can be detected
    in blood

8
Primary HIV Infection
  • Definition Acute HIV infection recent
    infection with HIV.
  • Recent Infection patients who are positive on
    HIV antibody testing (EIA), but have one of the
    following
  • A recent prior negative HIV test or
  • Results of detuned antibody test suggesting
    recent infection.

9
Couthino et al., Bulletin of Mathematical Biology
2001
10
Detecting Acute HIV Infections
Symptoms p24 Antigen HIV RNA HIV Ab Tests
0 1 2 3 4 5 6 7
8 9 10
Weeks Since Infection
11
PCR Testing of Pooled Sera to Identify Acute HIV
Infection (seronegative, PCR positive)
Source ISSTDR, 2007
12
How do we pick-up Acute HIV infection if routine
antibody tests are negative?
13
Acute Retroviral Syndrome
  • 40-90 of new HIV infections are symptomatic
  • Signs and symptoms typically begin 1-4 weeks
    following the exposure
  • Symptoms can last from days to several weeks, but
    usually lt14 days

Pilcher C et al. N Engl J Med 20053521873-1883 K
ahn JO, Walker BD. N Engl J Med.
199833933-39 Schacker T, et al. Ann Intern Med.
1996125257-264
14
Acute HIV Incubation Periods
31 Patients Average 14
days Range 5-30 days Sources Pilcher, JAMA
2001 Borrow, Nat Med 1997 Schacker AIM 1996
Lindback, AIDS 2001
10
8
6
Frequency
4
2
0
7
28
21
14
Days from Sexual Exposure to Onset of Symptoms
15
Non-specific Mononucleosis-like Signs and Symptoms
  • Fever
  • Rash
  • Oral ulcer
  • Weight loss
  • Loss of appetite
  • Headache
  • Fatigue
  • Adenopathy
  • Sore throat/ pharyngitis
  • Muscle and/or joint pain
  • Diarrhea
  • GI upset/nausea/
  • vomiting

16
Common Signs Symptoms
Study of 160 patients with primary HIV infection
in 3 countries
of patients
Vanhems P et al. AIDS 2000 140375-0381. 
17
Acute HIV and Symptoms
  • Schacker Kinloch-de Loes NC STD
  • Fever 93 87 48
  • Fatigue 93 26 37
  • Pharyngitis 70 48 30
  • Headache 55 39 26
  • Rash
    15
  • GI Symptoms
    37

Schacker TW, et al., AIM 1996 125257-64
18
Common Mis-diagnoses
  • Mononucleosis
  • Rocky Mountain Spotted Fever
  • Strep throat
  • Influenza
  • Viral illness
  • Secondary syphilis

19
Primary HIV Infection Pathogenesis
Symptoms
CD4 Cell Count (cells/mm³)
Plasma HIV RNA
CD4 Cell Count
4-8 Weeks
Up to 12 Years
2-3 Years
Primary
HIV Progression
AIDS
20
How do we pick-up Acute HIV infection if patients
dont have symptoms?
21
Our approach to Screening for AHI Specimen
pooling
  • Advantages
  • Seamless (almost) incorporation into HIV
    testing
  • Reduced cost
  • No real change in specificity
  • Universal application
  • Disadvantages
  • Requires large testing volume
  • Small loss in sensitivity
  • Logistics
  • Time to Dx and locating patient

22
STAT Testing Protocol
EIA/ Western Blot
-

HIV RNA testing
HIV Positive

-
F/U Testing (Ab HIV RNA)

-
Acute HIV
HIV Negative
23
Pooling and HIV RNA testing
90 individual HIV antibody negative specimens
9 intermediate pools (10
specimens)
1 master pool (90 specimens)
24
Distribution of Viral Loads in Ab Negative VCT
Specimens NC Testing Data 2002-2005 (n58)
16
14
12
10
n
8
6
4
2
0
2
3
4
5
6
7
8
log HIV RNA cp/ml
25
Low viral load specimens
16
14
12
10
n
8
6
4
2
0
2
3
4
5
6
7
8
log HIV RNA cp/ml
26
STAT Index Case Protocol
EIA/Ab () and WB () or EIA/Ab (-) RNA ()
STAT Case Possible acute HIV Infection
Confirmed Acute HIV STAT Notification
Confirmatory Test HIV Antibody and RNA Testing
EIA or Ab ()
EIA or Ab(-)
False RNA Positive
Repeat Testing
Ab -
STAT Post-Exposure Protocol
Immediate contact Dr. Leone UNC ID on call
Contact lt 72 hrs
  • DIS Interview
  • Referral to Care

STAT Contact Protocol
Contact lt 8 weeks
Contact gt 8 weeks
Routine Partner Notification Protocol
27
Notification of AHI in STAT 02-05
Time to notification improved to 11 days from
the time of testing (est. 39D into 80D
hyper-infectious period)
28
The STAT System
29
Screening and Tracing Active Transmission (STAT)
Program
  • From 2003-2006, 79 cases identified
  • 3 not located
  • 1 refusal for PCRS
  • 269 partners (from 75 AHI patients) identified
    within an 8-week exposure window
  • 174 (65) named
  • 132 (76) located
  • 95 (35) anonymous

30
STAT PCRS Outcomes (2003-2006)
46 (80) Counseled Tested
31
Why focus on Acute HIV Infection?
32
HIV Epidemic in NC
  • 7th leading cause of death for men and women ages
    25-44 in 2004
  • Approximately 10,600 HIV-infected NC residents
    were unaware of their status in 2005
  • HIV incidence in the US and NC is stable or
    increasing
  • NC ranked 2nd in the US for the number of AIDS
    cases from non-metropolitan areas

33
New Patients in the UNC ID Clinic
  • The median CD4 count was 202 cells/mm3 for
    patients initiating HIV care.
  • Majority (68) initiated HIV care within 1 year
    of their first positive HIV test.
  • 75 met guidelines for starting HIV treatment at
    their first visit.

NC DHHS- HIV/STD Prevention Care Branch
34
HIV viremia during early infection
Peak viremia 106-108 gEq/mL
HIV RNA (plasma)
Ramp-up viremia DT 21.5 hrs
HIV Antibody
HIV p24 Ag
p24 Ag EIA -
Viral set-point 102 -105 gEq/mL
HIV MP-NAT -
1st gen
2nd gen
HIV ID-NAT -
3rd gen
blip viremia
11
16
22
35
Primary HIV-1 Infection
1000 800 600 400 200 0
Early Opportunistic Infections
CD4 Cells

Late Opportunistic Infections
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Infection
Time in Years
36
Earlier HIV Diagnosis
  • Allows prompt entry into care
  • Initiation of ART prior to CD4 decline lt200
    improves mortality and morbidity
  • Management of STIs and other illness
  • Short-term behavioral changes can have a large
    impact on HIV spread
  • Improve natural history of disease with treatment
    during acute HIV infection?

37
Public Health Benefit
  • Acute HIV is the most infectious period
  • HIV RNA levels in the genital tract correspond to
    HIV RNA levels in the blood
  • Diagnosis is often missed even when patients are
    symptomatic with acute HIV infection

38
Plasma Viral Load and HIV Transmission Risk
  • Rakai (Uganda)
  • 453 HIV-disc. couples
  • 11.6 TR / year

Quinn 2000, NEJM 342921
39
Wawer, et al, JID 2005, 1911403
40
Viral Loads at Initial Detection Pilcher C et
al. N Engl J Med 20053521873-1883
10
Median Viral Loads
9
8
209,183
7
6
Log HIV RNA cp/ml
29,347
5
4
3
2
1
0
Established HIV (n66)
Acute HIV (n21)
41
HIV transmission prob. per male-female act
fold-change relative to wk 16 (calculated after
Chakraborty H, et al AIDS 2003)
16
14
12
10
Fold-change vs. wk 16
8
6
4
2
0
1
2
4
8
12
16
Weeks from Testing Positive for AHI
42
Risk of Transmission
5
Risk of Transmission Reflects Genital Viral
Burden
(1/30- 1/200)
HIV RNA in Semen (Log10 copies/ml)
4
(1/100- 1/1000)
3
(1/500 - 1/2000)
(1/1000 - 1/10,000)
2
Acute Infection
Asymptomatic Infection
HIV Progression
AIDS
43
Further Evidence That Primary HIV Infection
Accounts for a Large Proportion of HIV
Transmission
Source ISSTDR, 2007
44
Public Health Benefit
  • Identify HIV transmission networks
  • Allows real time prevention with index case and
    partners
  • Awareness of HIV status has been associated with
    decreased sexual risk behaviors

45
Lessons for Public Health
  • Acute HIV infection may be unexpectedly prevalent
    in common clinical scenarios
  • Immediate rather than deferred testing is key
  • HIV ELISA and HIV RNA
  • Sexual partners of acutely HIV infected
    individuals are at a markedly increased per-act
    risk of acquiring HIV

46
Lessons for Public Health
  • Linkage of acute HIV diagnosis with Emergent ID
    Consultation is paramount
  • Interpretation and counseling on test results
  • Extensive counseling of newly diagnosed patient
  • Facilitate linkage to care and services
  • Consideration of ART for interested patients
  • Acutely infected individuals provide public
    health officials with a unique opportunity to
    understand complex sexual networks

47
Screening and Tracing Active Transmission (STAT)
Program
48
November 1, 2002 May 28, 2008
49
STAT Acutes by County (11/1/2002-2/1/2008)
H
H
Case Count
0 1 2 (Burke, Franklin, Pitt,
Henderson, Onslow, Martin) 3 (Buncombe, New
Hanover) 4 (Robeson) 8 (Cumberland) 12
(Forsythe, Guilford) 15 (Wake) 15
(Mecklenburg)
Duke University Hospital
H
UNC Hospitals
H
50
Testing Site November 2002- May 2005
  • Tests Ab AHI
    () of AHI
  • HIV CTS 18,299 400 12
    (2.9) 21
  • STD 117,804 526
    27 (4.9) 48
  • FP 47,476 28
    -- --
  • Prenatal/OB 47,598 39 2
    (4.9) 3
  • Prison/Jail 7,158 57
    4 (6.6) 7
  • Other 37,073 320
    13(3.9) 22

51
The STD/HIV Connection
  • Susceptibility
  • Genital ulcers provide portal of HIV entry
  • Non-ulcerative STDs increase target cells
  • STD treatment has been shown to slow the spread
    of HIV infection (individual community)
  • Infectiousness
  • Presence of another STD increases amount of HIV
    in genital secretions
  • Treating STDs in PWHIV decreases
  • the amount of HIV they shed
  • how often they shed the virus

52
Potential impact of STI co-infection on
detection of AHI
HIV/STI Co-Infection Event
HIV RNA
4th gen. EIA
3rd gen. EIA
week 1
week 3
week 4
week 2
GC
Trichomoniasis
Chlamydia
Syphilis
HSV
ARS Symptoms
McCoy 0-014
53
STI Co-infections
  • 23 clients (30) had a concurrent STI

McCoy 0-014
54
STI Co-infections by Race, Gender, and Risk
Category
p 0.03
STI Co-infection
MSM
Male Hetero
Female
McCoy 0-014
55
Missed Opportunities in STD Clinics
  • HIV testing not offered to all
  • Risk factors for HIV either not obtained or not
    recognized
  • HIV testing not integrated into STD services
  • Primary HIV Syndrome unrecognized by patients and
    clinicians
  • Diagnostic test for Acute HIV Infections is not
    ordered

56
NC HIV Testing in STD Clinics
  • HIV testing to be offered to all STD clients for
    each new visit regardless of when last HIV test
    performed
  • DHHS policy to offer opt-out HIV testing
  • 2005 estimate 52 of NC STD clinic clients
    tested for HIV
  • Wake County ( 2nd largest STD clinic in North
    Carolina) with 80-85 with universal offering
    of HIV testing.
  • Wake County HIV testing increased to 90 with
    opt-out approach

57
Acute HIV and North Carolina STAT
58
Duke-UNC Acute HIV Infection Research Consortium
  • Research opportunities for patients with Acute
    and Recent HIV Infection
  • Treatment of Acute HIV Infection with Once Daily
    Atripla (24 month treatment study which supplies
    Atripla)
  • Longitudinal Assessment of Acute/Recent HIV
    Infection (Adds to limited scientific knowledge
    currently available regarding acute/recent
    infection)

59
Duke-UNC Acute HIV Infection Research Consortium
  • 3) CHAVI 001 Acute HIV-1 Infection Prospective
    Cohort Study
  • Acquire information to develop an HIV vaccine
  • The most relevant information may come from
    people with acute HIV infection and their
    partners

60
CHAVI Index Cases by County of Residence,
6/2007-2/2008 n18
Wake
Guilford
Forsythe
Durham
Halifax
1
2
2
1
D
7
U
1
1
1
2
Randolph
Martin
Pitt
Key
D
Duke University Hospital
U
Cumberland
UNC Hospital
61
CHAVI Partners By County of Residence,
6/2007-2/2008 n58
Wake
Durham
Hertford
Bertie
Forsythe
Guilford
Granville
Northampton
Pasquotank
1
1
1
1
1
3
2
1
D
U
17
1
1
1
1
9
1
Mecklenburg
1
Lee
Harnett
Craven
Martin
Scotland
Key
D
Duke University Hospital
U
Cumberland
UNC Hospitals
Other Partner Locations NC 3 SC 1 GA
2 WA 1 Abroad 2 Unk 6
62
Advatages to Dx and Care of AHI
  • 1.An HIV diagnosis per se results in subsequent
    risk reduction
  • 2. Initiation of HAART to reduce plasma and
    hence genital viral load thus reducing
    transmission potential
  • 3. As we identify more undiagnosed HIV and more
    are successfully placed on HAART, transmission
    will shift even more to AHI
  • 4. As frequency of HIV testing increases, we will
    idenitfy more AHI
  • 5.Opportunity for short term behavior change
    (period of high infectivity of weeks)

63
Conclusion
  • Make HIV testing routine
  • Opt-out HIV Testing for all STD clients
  • Screen all STD clients for AHI
  • Include AHI in the Differential Dx of Acute Viral
    Syndrome in all Sexually Active Adults

64
Conclusion
  • AHI is a true Public Health Emergency!
  • AHI detection and case investigation puts
    identification of HIV at leading edge of
    transmission
  • Opportunity for both early diagnosis and
    prevention
  • Report all AHI cases within 24 hrs

65
laboratory
66
Given this VL distribution Analytical vs.
Clinical Sensitivity
67
Requirement for Analytical Sensitivity is Less
Stringent than for VL Monitoring
  • To be recommended as part of (all) general HIV
    testing, a NAAT would likely need 95 detection
    at viral loads the equivalent of 5,000 to 10,000
    HIV RNA copies per mL
  • Better sensitivity required for effective
    analysis of pooled specimens

68
Detection of Acute HIV
  • Acute HIV infections (first 2-3 months) are
    estimated to account for as much as half of all
    HIV transmission (Wawer at al JID 2005)
  • They represent 0-10 of detectable infections
    presenting for HIV testing
  • Real-time recognition of acute infections creates
    opportunities for highly targeted treatment,
    prevention and surveillance activities

69
Detection of Acute HIV
  • Detuned assays can identify recent
    seroconversion, but with a 1-2 month delay from
    infection. These also do not identify additional
    cases over routine antibody tests.
  • Real-time diagnosis of acute HIV depends on the
    identification of HIV antigens (e.g., p24) or
    nucleic acids (NAAT) in the absence of HIV
    antibodies.

70
The Gold Standard for Acute Screening is RNA
Group Testing of Ab - Specimens
Ab screen
-

-
Ab confirm

NAAT screen
-

HIV Negative
Established HIV Positive
Possible Acute HIV
Pilcher, CD et al. JAMA 2002288216-221
71
Testing to Identify Acute HIV
  • NAAT is highly sensitive and with pooling, may be
    made specific.
  • However, even pooled NAAT may be inefficient in
    high prevalence areas (gt5) and is technically
    demanding.
  • Fourth generation HIV ELISAs detect both
    antigen and antibody simultaneously
  • Easy to perform
  • Equipment available in most HIV laboratories

72
Window Periods for HIV Tests
Stekler J. et al CID 2007
73
Commercial Assays Comparative Timing of Detection
of Acute HIV Infection
Source HPA -UK
74
  • Reducing time to case identification

75
Summary Pooling vs. Individual NAAT
  • Pooled screening (even with minipools) makes
    testing possible by reducing costs and improving
    predictive value
  • More complex but more efficient for through put
    and cost
  • Single specimen NAAT screening should be reserved
    for situations where the pre-test likelihood of
    acute HIV infection is gt/ 1 (e.g., suspected
    AHI, ?ED/urgent care screening)

76
Opportunities for New Technologies and
Approaches
  • Need to reduce time to identification of AHI
  • NC median time to identification is 9D
  • Fast Track can reduce time to 2-4 days
  • Current POC HIV tests only test for Ab
  • 4th generation EIA can reduce time to Dx and
    reduce cost
  • Strategy may need to combine individual NAAT or
    discrepant POC 3rd generation EIA to identify AHI

77
Rapid Antibody Testing
  • The Good
  • Makes testing feasible in non-traditional
    settings
  • Highly effective for outreach situations (needle
    exchange, bathhouse testing,
    street-corner outreach)
  • Increases receipt of positive HIV test results
  • Where HIV results notification (PCRS) not in
    place
  • May increase requests for HIV testing
  • The Not So Good
  • Confidentiality
  • Cost 2-3x ELISA Ab tests
  • May defer resource allocation/personal to HIV
    negatives
  • May miss AHI
  • Requires Confirmation

78
Alternative Approaches
  • North Carolina AHI referral network
  • Educate community providers about AHI
  • Educate high risk community about AHI
  • Linkage of ED testing to ID clinic and local
    health departments…… strongly encourage
    partnerships . EDs will test if burden for
    referral to care is met.
  • Raise awareness of 3rd generation EIA / WB I as
    possible AHI

79
Cost-effectiveness of the STAT Program Decision
Tree Analysis
  • The expected savings from averting new HIV cases
    offset 22 of the testing costs
  • Overall cost per QALY of 4,345
  • Conclusion the program appears to be well below
    the cost effectiveness threshold of 50,000 which
    is often used as an indicator of good public
    health investment opportunities in the US.
  • Still, cost a barrier for new programs

80
Targeting NAAT Screening by Site
  • Over 2 years, at 135 public testing sites in NC,
    325 acute and recent infections were identified
    among 224,124 testing clients (66 females, 4
    MSM)
  • Only 1/3 acute clients had HIV symptoms at
    testing
  • There were no cases in 48 of 100 counties
  • Targeted Screening
  • If NAAT used only in HIV CT, STD, prison, and
    field visit sites in counties with ? 1 case,
    95.4 of acute cases identified testing only
    54.0 of the population with NAAT
  • Testing only in STD clinics identified 40.1 of
    cases while testing 41.4 of the population.

81
Targeting is necessary but be wary of
preconceptions
  • It is possible to construct a targeting algorithm
    for NAAT testing based on knowledge of local
    incidence, prevalence and individual risk factors
    associated with having recent infection
  • Detuned test results can be used to develop
    NAAT targeting criteria
  • A priori assumptions about who to test with NAAT
    are likely to be incorrect (i.e., limiting
    testing to only high risk clinics, or to
    symptomatic clients would be counterproductive)

82
Opportunities for New Approaches
  • Need to reduce time to identification of AHI
  • NC median time to identification is 9D
  • Fast Track can reduce time to 2-4 days
  • We are implementing Fast track to all STD clinics
    based on symptoms and requiring STAT clinician
    approval

83
Fast Track Targeted AHI Testing
  • Screen all clients for HIV Ab
  • Target
  • Problem Which symptoms (fever?)
  • What time period (2-4
    wks)?
  • What duration ( gt2
    days)?
  • Symptoms at best will
    detect 40
  • - Targeted testing
  • Risk based ( i.e. MSM, anal/vaginal
    sex in past 2 weeks,etc )
  • Symptoms based (Fever for gt2 days
    within past 4 weeks)
  • Site based ( prevalence 0.5 or
    type STD,CTS, etc.)
  • 3. Need for further research to define
    symptom screen and develop predictive models for
    targeted AHI testing

84
Opportunities for New Technology
  • Current POC HIV tests only test for Ab
  • 4th generation EIA can reduce time to Dx and
    reduce cost
  • Plan to do real time side by side comparison of
    NAAT pooling with 4th generation assay
  • May need to combine individual NAAT or discrepant
    POC 3rd generation EIA to identify AHI

85
Biology
86
Determining the Genetic Linkage of HIV-1 Subtype
B Transmission Pairs Analyses of Viral env
Sequences From Donor and Recipient
  • Jeffrey A. Anderson, MD-PhD
  • University of North Carolina

87
Background
  • A genetic bottleneck occurs during mucosal
    transmission, resulting in a subset of viruses
    responsible for transmission of HIV.

DONOR
RECIPIENT
88
Background
  • Determining the genetic composition of the
    transmitted virus is critical to developing
    insight into disease progression, HIV
    pathogenesis, and candidate vaccines.
  • Key questions
  • From the donor quasispecies, what are the
    properties of the specific variant(s) being
    transmitted?
  • Are genital tract secretions a separate
    compartment from blood plasma?

89
3 MSM Transmission pairs from CHAVI 001 Donor
vs. Recipient
of env amplicons blood
of env amplicons semen
Sampling Time Weeks Post-infection
ELISA
WB
Stage
174 D1 150 R1
148 D2 40 R2
135 D3 81 R3
269
86
90
Experimental design
Identify patients with acute HIV-1 infection, and
sexual partners through contact tracing
After informed consent, obtain blood plasma and
semen/cervicovaginal lavage
Isolate HIV-1 viral RNA from blood/semen/CVL fluid
Generate a copy of the viral DNA and amplify by
PCR
Direct DNA sequence analysis to determine
characteristics of HIV
91
Chromatograms from a single DNA sequence
92
Donor env blood plasma populations are
heterogeneous
D1
D2
D3
93
Recipient env blood plasma populations are
homogeneous
22 identical sequences
33 identical sequences
3
2
3
10
2
3
R1
R2
R3
94
Phylogenetic analysis of D1/R1
  • Blood and semen populations are well-mixed

95
Phylogenetic analysis of D1/R1
  • Blood and semen populations are well-mixed
  • However, a subset of duplicated semen
  • amplicons suggests selective outgrowth







96
Phylogenetic analysis of D1/R1
  • Blood and semen populations are well-mixed
  • However, a subset of duplicated semen
  • amplicons suggests selective outgrowth
  • No blood amplicons were duplicated




Unique
Duplicate

Blood
Semen

P lt 0.0001

97
Phylogenetic analysis of D1/R1
  • Blood and semen populations are well-mixed
  • However, a subset of duplicated semen
  • amplicons suggests selective outgrowth
  • No blood amplicons were duplicated




Unique
Duplicate

Blood
Semen

P lt 0.0001
4. R1 is clearly genetically linked to D1
semen (99 nt identity), and did not
arise from a duplicated semen sequence

98
Summary
  • Genetic linkage of 3 subtype B transmission pairs
    was confirmed by SGA and DNA sequence analysis.
  • All donor (D1-D3) populations had heterogeneous
    env populations, although D1 had low
    heterogeneity.
  • A single variant was transmitted to each
    recipient (R1-R3).
  • Semen populations were well-dispersed among blood
    populations.
  • Clusters of duplicated sequences in semen of D1
    and D3 suggest outgrowth of specific variants.
  • These data suggest that semen sequences, in
    general, represent sequences present in blood
    however, semen populations can be disrupted by
    selective outgrowth.
  • Analyses of additional transmission pairs are
    ongoing and will lead to a greater knowledge of
  • compartmentalization of viral sequences within
    semen vs. blood
  • the specific viral variant(s) transmitted from
    donor to recipient
  • viral sequences important for HIV-1 vaccine
    design

99
Acknowledgments
  • Ron Swanstrom and lab members
  • Beatrice Hahn
  • Brandon Keele
  • Jesus Salazar
  • Susan Fiscus and lab
  • Julie Nelson
  • Myron Cohen
  • Lihua Ping
  • Kristen Dang and Christina Burch
  • CHAVI 001 Clinical Core
  • NC Dept. of Health and Human Services
  • DIS Training Program and Officers

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North Carolina may have lower attribution of AHI
on Transmission
27 individuals (12) were in closely
related (lt1 divergence) clusters Still, a
4-6 week period accounts for 10-15 of
Transmission
Frost s et al. CROI 2007
102
Network Analysis Project SNAP
  • Acutely/Recently infected MSM and high risk
    HIV-negative men recruited for in-depth ACASI
    interview and qualitative interview
  • Respondent driven sampling to derive sexual and
    social network (2 generations)
  • Better understanding of network formation,
    HIV/STD transmission, sex partner selection and
    Internet use among NC MSM

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If you have an STD, Get Tested for HIV. Early
Detection is Best! Learn to Recognize IT. Tell a
Friend. Acute HIV is Easily Misdiagnosed. IT CAN
BE MISTAKEN FOR COMMON ILLNESSES
Common Symptoms of Acute HIV High Fever
Rash Fatigue Swollen Glands Sore Throat
Nausea/Vomiting Night Sweats Symptoms usually
appear about 2 weeks after exposure What Puts You
At Risk? Unprotected Sex Sharing Needles The
Acute HIV Program 919-966-8533
  • If you suspect you may have Acute HIV, get tested
    at your Local Health Department or at your
    doctors office.
  • FREE Screening for acute HIV is done on all HIV
    tests done through the NC Health Departments
  • Screening for acute HIV can be done at your
    doctors office ask for an HIV RNA test in
    addition to the standard HIV antibody test.
  • SPREAD THE WORD - NOT HIV

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Conclusions
  • HIV antibody screening is a necessary first step
    in targeting prevention activities
  • Assays able to detect antibody-negative
    infections should be incorporated into current
    HIV screening/testing
  • NAAT may not be reasonable for low-risk routine
    screening in well patients and low prevalence
    populations
  • Models for establishing criteria for targeting
    NAAT are need
  • 4th generation EIAs may present an alternative
    for diagnosis of acute HIV infection and merit
    urgent large-scale clinical evaluations

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Window Periods for HIV Tests
Stekler J. et al CID 2007
109
Tests to DX HIV
  • Antibody ELISA 47
  • Western Blot 212
  • p24 Antigen 38
  • Individual HIV RNA PCR 218
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