Download - HIV Diagnostic Tests
![Page 1: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/1.jpg)
HIV Diagnostic Tests
Bernard M. Branson, M.D. Associate Director for Laboratory Diagnostics
Division of H IV/AIDS Prevention Centers for Disease Control & Prevention
The views expressed in this presentation are those of the author and do not necessarily represent those of the Centers for Disease Control and Prevention
![Page 2: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/2.jpg)
Generations
![Page 3: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/3.jpg)
1st and 2nd Generation EIA Plasma/serum (1 h/37o C)
Plasma/serum
Color reagent
Antigen 1st - Viral lysate 2nd – Recombinant proteins or synthetic peptides
IgG HIV antibody
enzyme
anti-human IgG
Detects HIV IgG
Enzyme- detection
![Page 4: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/4.jpg)
EIA
Western blot
IFA
![Page 5: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/5.jpg)
3rd Generation “Sandwich” EIA
Antigen: Recombinant proteins or synthetic peptides Enzyme-
detection
Color reagent
Plasma/serum HIV antibody
enzyme
HIV antigen
Detects HIV IgM or IgG
IgG IgM
![Page 6: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/6.jpg)
4th Generation Combo EIA
Color reagent
Enzyme- detection
HIV antigen p24 antibody
Plasma/serum HIV antibodies p24 antigen
HIV antigen
p24 antibody
Detects IgM or IgG
antibody or p24 antigen
i
![Page 7: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/7.jpg)
HIV Infection and Laboratory Markers
HIV RNA (plasma) HIV Antibody
0 10 20 30 40 50 60 70 80 90 100
HIV p24 Ag
22
1st gen
2nd gen
3rd gen
Days
Modified after Busch et al. Am J Med. 1997
Infection
9
4th gen
![Page 8: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/8.jpg)
1985 Abbott
HIV-1 EIA
1987 Vironostika
EIA
1992 Abbott
HIV-1/HIV-2 EIA
2000 Genetic Systems
HIV-1/HIV-2 Peptide EIA
2002 OraQuick
HIV-1/HIV-2 Rapid Test
2003 GS HIV-1
HIV-2 Plus O EIA
2004 Multispot
HIV-1/HIV-2 Rapid Test
2006 Aptima
Qualitative RNA
2006 Advia Centaur
1/O/2 CIA
2008 Ortho Vitros
HIV 1+2 CIA
1991 Cambridge
Western blot
1992 Fluorognost
IFA
1998 Genetic Systems
rLAV (HIV-1)
2003 Unigold Reveal
HIV-1 Rapid Tests
2010 Abbott
Architect Ag/Ab
Combo CIA
2011 Bio-Rad Ag/Ab Combo
EIA
2010 INSTI HIV-1
Rapid Test
2009 Avioq HIV-1
EIA
3rd & 4th gen lab screening tests
2nd gen rapid tests 1st gen confirmatory
![Page 9: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/9.jpg)
Uni-Gold Recombigen 2003
Multispot HIV-1/HIV-2 2004
Reveal G3 2003
OraQuick Advance 2002
Clearview Complete HIV 1/2 2006
Clearview HIV 1/2 Stat Pack 2006
![Page 10: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/10.jpg)
Rapid HIV Test Results without
Rapid Test Kits
![Page 11: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/11.jpg)
On-board Refrigeration of Multiple Different Assays
Random Access Multiplatform analyzers for HIV testing
![Page 12: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/12.jpg)
STAT sample requests without pausing Results in < 60 minutes
Random Access Multiplatform analyzers for HIV testing
![Page 13: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/13.jpg)
ADVIA® Centaur™ H IV 1/O /2 Enhanced (EH IV) Chemiluminescent
immunoassay
3rd generation format - H IV-1: gp41, p24 - H IV-2: gp36 - group O
Time to result < 1 hour
FDA-approved July 2006
![Page 14: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/14.jpg)
Ortho VITROS ECi/ECiQ Chemiluminescent
immunoassay
3rd generation format - H IV-1: gp41, gp120, p24 - H IV-2: gp36 - group O
Time to result < 1 hour
Repeat only borderline results
FDA-approved March 2008
![Page 15: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/15.jpg)
Chemiluminescent immunoassay
Detects p24 antigen and H IV antibody
Time to result: 29 minutes
FDA-approved
June 22, 2010
Abbott Architect 4th Generation Ag/Ab Combo Assay
![Page 16: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/16.jpg)
APTIMA Qualitative HIV-1 RNA Assay Aid to H IV-1 diagnosis
Diagnosis of acute H IV-1
infection in antibody-negative persons
Confirmation of H IV-1 infection in antibody-positive persons when it is reactive
FDA-approved July 2006
![Page 17: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/17.jpg)
Bio-Rad GS HIV Combo Ag/Ab EIA
Microwell plate EIA
3rd generation format: - HIV-1: gp160 - HIV-2: gp36 - Group O
p24 antigen
FDA-approved July 25, 2011
![Page 18: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/18.jpg)
Relative Seroconversion Sensitivity
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
-50 -40 -30 -20 -10 0 10 20 30
Genprobe
Architect 4th
BioRad 4th
Advia 3rd
Vitros 3rd
Abbott 3rd
BioRad 3rd
Insti
Multispot
Reveal
Statpak
Complete
Unigold
Oraq Adv
Cum
ulat
ive
frequ
ency
of p
ositi
ve te
sts
days to WB positive
26 seroconverters were analyzed with 14 tests 17 seroconverters with WB positive used for cumulative frequency analysis
![Page 19: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/19.jpg)
Sequence of Test Positivity Relative to WB 166 specimens, 17 Seroconverters - 50 % Positive Cumulative Frequency
Modified from Masciotra et al, J Clin Virol 2011
Days before WB positive
WB
posi
tive
APT
IMA
(-26)
GS
1/2+
O (
-12)
Mul
ti-Sp
ot (
-7)
Reve
al G
3,
(-6)
Viro
nost
ka (+
2)
Ora
Qui
ck (-
1)
Uni
gold
(-2)
25
20
10
5 0 15
Arch
itect
Ag/
Ab C
ombo
(-2
0)
COM
PLET
E H
IV-1
/2 (
-5)
HIV
-1/2
STA
T-PA
K (-
5)
Advi
a (-
14)
Vitr
os (
-13)
INST
I (-9
)
Bio-
Rad
Ag/
Ab C
ombo
(-1
9)
and Owen et al, J Clin Micro 2008
Avio
q
Det
erm
ine
Ag/A
b Co
mbo
(-1
5)
![Page 20: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/20.jpg)
Acute Infections in MSM detected by RNA only
0.3% of 14,005 frequently tested MSM in Seattle STD clinic; 20% of all HIV infections detected
26 (74%) of 35 AHI cases detected in LA at MSM clinic; 25% of all HIV infections detected
0.08% of 21,425 STD clinic patients in New York City; 9% of all HIV infections detected; 94% were MSM
- Stekler et al, Clin Infect Dis 2009
- Shepard et al, MMWR 2009
- Patel et al, Archives Int Med 2010
![Page 21: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/21.jpg)
RNA vs. 4th Generation Ag/Ab Assay
RNA+ / 3rd gen-negative specimens detected by 4th generation EIA: 38 of 46 (83%) – Australia* 10 of 14 (71%) – CDC AHI study** 51 of 61 (84%) – CDC panel***
4 days after RNA – 9 seroconversion panels***
* Cunningham P, HIV Diagnostics Conf 2007 ** Patel P, CROI 2009 *** Owen M, CROI 2009
![Page 22: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/22.jpg)
On the Horizon…
![Page 23: HIV Diagnostic Tests](https://reader033.vdocuments.net/reader033/viewer/2022051204/6278349f71865b19ec2b7bfe/html5/thumbnails/23.jpg)
Ag/Ab Rapid Test
Point-of-careHIV-1/2 antibody differentiation assay with
automated reader
Point-of-care finger-stick viral load and CD4
analyzer