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New tools for diagnosis and
surveillance
Beth A Skaggs, PhD
Laboratory Advisor, Division of Global HIV/AIDS
CDC-Mozambique
AIDS MEDICINES AND DIAGNOSTICS (AMDS)
ANNUAL STAKEHOLDERS AND PARTNERS MEETING
7 – 8 May 2013
Starling Hotel, Geneva, Switzerland
Dual HIV – Syphilis Rapid Test
Limited Antigen Avidity HIV Incidence Test
Low Cost HIV Drug Resistance Assay
Mr. Javan Esfandiari
Chembio Diagnostic Systems, Medford, NY
2012 HIV Diagnostics Conference, Atlanta, GA
HIV-Syphilis Dual Path Platform
Rapid Diagnostic Test
Dual Path Platform
Addition of a recombinant
treponemal antigen to the
ChemBio HIV1/2 rapid test
Seeking FDA approval
Evaluated in CDC lab with
good performance (B.
Parekh, personal
communication)
Sample
Type N
DPP HIV Syphilis
Assay
Syph Trep EIA Syph RPR Overall
Calculations
Syph
Trep (-)
Syph
Trep (+)
- + - +
Syph Trep
Specificity=
97%
95% CI;
95.7-98%
Blood 330 320 10 ND ND 330 0
Serum 202 195 7 194 8 202 0
Plasma 407 396 11 386 21 407 0
Total 939 911 28 N/A N/A 939 0
Source: Esfandiari J. 2012. Abstract, 2012 HIV Diagnostics Conference, Atlanta, GA
Sample
Type N
DPP HIV Syphilis
Assay
HIV 1/2 EIA DPP test specificity
HIV1/2
(-)
HIV 1/2
(+) - +
HIV
1/2 CI
Blood 330 330 0 330 0 100% 98.9-100%
Serum 202 202 0 202 0 100% 98.2-100%
Plasma 407 407 0 407 0 100% 99.1-100%
Total 939 939 0 939 0 100% 99.6-100%
DPP HIV
Syphilis
Line
N # Positive Sensitivity 95% CI
HIV 398 398 100% 99.1-100%
Syphilis Trep 83 83 100% 95.7-100%
*Compared to ELISA followed by RPR confirmation
Bharat S. Parekh, PhD International Laboratory Branch
Division of Global HIV/AIDS
Centers for Disease Control and Prevention, Atlanta, GA
Development of a Limiting Antigen
Avidity EIA
to Estimate HIV-1 Incidence
Tracking the leading edge of the epidemic
Monitoring impact of prevention efforts
“Acute infection” based on p24 RNA detection
BED-Capture EIA initially developed and commercialized
(Calypte Biomedical Corp, Oregon)
Mean duration of recency 162 days
New and improved assays based on antibody avidity
Mean duration of recency 141 days
2-well avidity assay to calculate Avidity Index (AI)
Singe-well limiting antigen avidity assay (LAg-avidity)
LAg-avidity in lateral flow, rapid test format (preliminary
stages of development)
Specimens include- serum, plasma or finger prick in
case of RT
Use of recombinant gp41 antigen reduces impact of
HIV subtype variation
Cohort
N. of Subjects
(number of
specimens)
HIV-1 Subtypes
Mean Recency
Period (95% CI)
in days
Amsterdam &
Trinidad 32 (170) B 132 (104-157)
Ethiopia 23 (143) C 139 (106-178)
Kenya 34 (80) A, D 143 (103-188)
All 89 (393) A, B, C, and D 141 (119-160)
Source: Parekh BS et al. 2011. AIDS Res Hum Retroviruses 27:265-273.
Frequency of False Recent Classification (%)
Cohort BED-CEIA LAg-Avidity EIA
US, AIDS (n=261) 11 (4.2%) 0 (0%)
Thailand, AIDS + TB
(n=128) 1 (0.8%) 0 (0%)
Cote d’Ivoire, AIDS + TB
(n=99) 2 (2%) 1 (1%)
OVERALL (n=488) 14 (2.9%) 1 (0.2%)
Source: Duong YT et al. 2012. . Plos One 7:1-9.
Chunfu Yang, DVM, PhD
International Laboratory Branch
Division of Global HIV/AIDS
Centers for Disease Control and Prevention, Atlanta, GA
Sensitive for multiple HIV-1 subtypes and
recombinants
Accessible costs
Simple specimen collection methods
No cold chain requirements for sample shipment
ViroSeq™ HIV-1 (Abbott)
TRUGENE® HIV-1 (Siemens)
• approved for HIV-1 subtype B
• instrument specific
• expensive
• specimen: plasma (VL > 1000 copies/ml)
97.1% 98.1%
93.2%
85
90
95
100
N=103, median VL=4.76, range 3.03-6.47 log 10 )
Frozen plasma Frozen DBS DBS at Ambient T 2-wk
P>0.05 P>0.05
Fisher’s exact test
23.83
1.36
37.56
3.77
0.3 1.51
0.45
13.88 1.06 0.6 0.15
0.9 0.45 0.3
2.26 0.15 3.62
7.84
A1 B C D F G
H 01_AE 02_AG 03_AB 06_cpx 07_BC
08_BC 09_cpx 10_CD 13_cpx UC URF
N = 663
Timepoint N Previous
ART
CD4
cells/ml
Baseline
VL
# with
VL>150
copies/ml
#
genotyped
# with any
resistance
mutations
Baseline
603
(57.2%
female)
9* 145 162,181 603
569/575
with VL
results
23 (4%)
12 months
after ART
initiation
503
(436 alive
on ART
and 67
defaulters)
N/A N/A N/A
35/395
with HIV
RNA
determinati
ons
(8.8%)
35/35 with
VL results 24 (6%)
Source: Wadonda-Kabondo et al. 2012. Clin Infect Dis. 53:S362-368
Innovative and accessible HIV diagnostic tools are
making important contributions to our knowledge of the
HIV epidemic
Mulitiplex rapid tests can be useful tools for diagnosis
in RSL and can simplify supply chain, training, quality
assurance and burden on health care workers
HIV Incidence assays appropriate for multiple HIV-1
subtypes can help guide HIV transmission prevention
and control efforts
Affordable approaches to monitoring HIV DR can be
added on to periodic population or sentinel HIV surveys
to provide essential data on drivers of HIV DR
Recommended