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

Courtesy of B. Parekh

Courtesy of B. Parekh

Courtesy of B. Parekh

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)

Source: Zhou et al. PLoS One. 2011; 6(11): e28184

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

24 countries:

14 Africa, 5 Latin America, 3 Asia and 2 North America

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

CDC HIV-dB supports for global HIV

genotyping surveillance

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

Beth Skaggs

Email: Skaggsb@mz.cdc.gov