HIV Diagnostics and Acute HIV

Sonya Heath, MD

University of Alabama @ Birmingham

2017

Objectives

• Changes in HIV testing algorithms

– Review the 2006 CDC Testing Recommendations

– 4th generation HIV tests

– Changes in confirmatory testing- Geenius

• Acute HIV Infection

– Test of choice

– Understanding of the window period

2006 CDC HIV Testing Recommendation

• Routine, voluntary HIV screening for all

persons 13-64 in health care setting, NOT

BASED ON RISK

• Repeat screening with persons of known risk

annually

• OPT out screening with opportunity to ask

questions and option to decline

• No separate consent

HIV Testing Immunology Basics

• Antigen- viral particles or proteins that elicit an immune

response.

– HIV Ag- p24

– HIV RNA (viral load)

– Present at the time of infection

• Antibody- immune response that recognizes foreign material

– IgM

– IgG

– Generated by the host-

– delayed several weeks after infection

HIV Tests

Generation Antibody Antigen

First IgG

Second IgG

Third IgM + IgG

Fourth IgM+ IgG p24

MedMira Reveal G3

OraQuick

AdvanceClearview Complete

Clearview Stat PakINSTI

Multispot

HIV-1/HIV-2

Modified from B. Branson CDC

2nd Generation

Chembio DPP HIV

½ Assay

Courtesy B. Branson CDC

3rd Generation “Sandwich” Immunoassay

Antigen:

Recombinant proteins or

synthetic peptidesEnzyme-

detection

Color

reagent

Plasma/serumHIV antibody

enzyme

HIV antigen

Detects HIV

IgM or IgG

IgG IgM

Abbott Architect Ag/Ab Combo Bio-Rad Ag/Ab Combo

AntibodyAntigenControl

Determine Combo Ag/Ab Rapid Test

4th Generation: Combined Ag/ Ab HIV Assay

20112010

2013

4th Generation Combo Immunoassay

Color

reagent

Enzyme-

detection

HIV antigen

p24 antibody

Plasma/serumHIV antibodies

p24 antigen

HIV antigen

p24 antibody

Detects IgM

or IgG

antibody or

p24 antigen

Courtesy B. Branson CDC

Detection Range of HIV Tests

ACUTE

SYMPTOMS

HIV-1 RNA NAAT (2006)

HIV EIA 4th Generation

(Ag/Ab)

HIV EIA 3rd Generation

HIV EIA 1ST (1985) &

2ND Generation

Western Blot

1 2 3 4 5 6 7Weeks After Infection

Confirmatory Testing: Geenius

HIV-1/2 Combination Ag/Ab immunoassay

Geenius HIV-1/HIV-2 antibody assay

(-)(+)

HIV-1 (+)

HIV-2 (-)

HIV-1 antibodies

detected

HIV-1 (-)

HIV-2 (+)

HIV-2 antibodies

detected

HIV-1 (-) or indeterminate

HIV-2 (-)

NAT

NAT (+) Acute HIV-1 infection

NAT (-)Negative for HIV-1

Negative for HIV-1 and HIV-2

antibodies and p24 Ag

HIV-1 (+)

HIV-2 (+)

HIV antibodies

detected

CDC/APHL Proposed New HIV

Testing Algorithm

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 4th

gen

Acute HIV Infection

HIV Infection and Laboratory Markers

Primary HIV Infection: Signs &

Symptoms

• 40-90% of patients will be symptomatic

• A mononucleosis-like illness of non-specific signs and symptoms

• Signs and symptoms typically begin 1-4 weeks post-exposure

• No specific constellation of signs or symptoms can differentiate acute HIV from other illnesses

• High index of suspicion is criticalKahn JO, Walker BD. N Engl J Med. 1998;339:33-39.

Schacker T, et al. Ann Intern Med. 1996;125:257-264.

Acute Retroviral SyndromeSymptoms All Patients Acute HIV Early HIV p value

n=55* n=25 n=30

Systemic- no. (%) 48 (87) 25 (100) 23 (77) 0.010

Fever 37 (67) 23 (92) 14 (47) 0.000

Chills 21 (38) 16 (64) 5 (17) 0.000

Fatigue 26 (47) 17 (68) 9 (30) 0.005

Rash 19 (35) 10 (40) 9 (30) 0.437

Lymphadenopathy 25 (45) 13 (52) 12 (40) 0.373

Respiratory- no. (%) 30 (55) 18 (72) 12 (40) 0.018

Sore throat 22 (40) 13 (52) 9 (30) 0.097

Cough 12 (22) 9 (36) 3 (10) 0.026

Gastrointestinal- no. (%) 23 (42) 17 (68) 6 (20) 0.000

Vomiting 13 (24) 10 (40) 3 (10) 0.012

Diarrhea 13 (24) 10 (40) 3 (10) 0.012

CNS- no. (%) 20 (36) 15 (60) 5 (17) 0.002

Headache 17 (31) 12 (48) 5 (17) 0.019

Dizziness 6 (11) 5 (20) 1 (3) 0.082

*Missing data n = 3

Primary HIV Infection

Rash Mucosal Lesions

Trunk and face > limbs

Small pink macules

Oral ulcers, thrush

(Kahn, NEJM, 1998)

Oral Ulcers in Acute HIV Infection

From: Walker, B. 40th IDSA, Chicago 2002.

HIV

RN

A in S

em

en

(Log

10

copie

s/m

l)

2

3

4

5

1/1000 -

1/10,000

1/500 -

1/2000

1/100-

1/1000

1/30-

1/200

Acute Infection: Increased Risk of Sexual

Transmission of HIV

Cohen & Pilcher, J Infect Dis. 2005

Virus 75-750 times more

infectious

Ma, J Virol 2009

Routine Testing Insufficient for

Diagnosing Acute HIV

106

105

104

103

102

101

+

_

HIV

RN

AH

IV-1

An

tibo

die

s

Exposure

0 20 30 40 50

Symptoms

Days

HIV RNA

Ab

10

Window Period

Acute HIV Summary

If you suspect acute HIV, the correct test

to order is a viral load or 4th Gen Ag/Ab

The opportunity for diagnosis is brief

Symptoms which prompt healthcare visits

Self limited

Often unrecognized or attributed to other

illnesses

Acute HIV is highly infectious due to

exceedingly high viral loads

Notify the Health department for rapid

partner notification

HIV Diagnostics Summary

• The new testing algorithm no longer recommends

western blot or Multi-spot as the confirmatory HIV

test

• The Geenius test, which is a point of care, rapid test

is now recommended for confirmation of HIV and

replaced Multi-spot for the confirmatory test Where

available, 4th Generation combination Ag/Ab tests

are recommend as the first line test

• ALL DISCORDANT RESULTS SHOULD

REFLEXIVELY RESULT IN HIV VIRAL LOAD

TESTING TO RULE OUT ACUTE HIV

Acknowledgements:Bernie Branson CDC

James Galbraith

Suzanne McCluskey

Sonya Heath

slheath@uabmc.edu

205-996-2371