HIV Guideline 2016

Sakchai DettrairatDivision of Clinical Immunology

Department of Medical Technology

Faculty of Associated Medical SciencesChiang Mai University

J Clin Virol, Volume 54, Issue 1, May 2012, p42-47

Appearance of HIV markers in early HIV infection

Objectives• Blood and blood products safety.

• Screening of donors of sperms, organs and tissues.

• Diagnosis of HIV infection in clinically suspected cases.

• Voluntary counseling and testing (VCT).

• Epidemiological surveillance.

• Research and surveys.

Diagnosis of HIV Infection

Diagnostic Tests• Anti-HIV Antibody Test

• HIV p24 Antigen Test

• HIV Nucleic AcidAmplification Tests(NAAT)

Screening Tests

EIA/ELISA or CIAs

Simple/Rapid Tests

Confirmatory or Supplemental Tests

WB

IFA

HIV Testing

Generation Antigens/antibodies Comment/characteristic

First Antigens from HIV lysates Lack of sensitivity and specificity

Second Recombinant proteins and/or synthetic peptides

Improved sensitivity andproduction of combined HIV-1/HIV-2 assays

Third Use labeled antigen asconjugate

Very high sensitivity and able to detect IgM Ab; reduced the window period considerably

Fourth Detection of both HIV antigen (p24) and Ab

Further reducing the window period

Generation of anti-HIV EIAs

rHIV Ag and synthetic peptides

Enzyme conjugated HIV Ag

IgG AbIgM Ab

Substrate Reactive End Product

(color/light)

Env/Core Ags

E E EE

EE

Third generation Double Antigen Sandwich ELISA for detection of HIV Abs

Anti-p24 AbrHIV Ag/ peptide

Enzyme-conjugatedAnti-p24 Ab

p24 Ag

Enzyme conjugated HIV Ag

Anti-HIV Ab

Substrate Reactive End Product

(color/light)

EE

E EE

E

Fourth generation Sandwich ELISAfor detection of both HIV Ag and Abs

Lateral flow strip

• Qualitative test to detect Abs

to HIV-1/2

• Simple or Moderate Complexity

• Serum/Plasma/Whole blood

• Visual Reading in 10-15 min

• Testing formats

– Immunofilteration (flow through)

– Immunochromatography

(lateral flow)

– Dot immunoassay,

– Particle agglutination

Rapid HIV Tests

HIV Immunochromatographic Test (Lateral Flow Strip)

• Tests for screening of blood and blood

products

–Sensitivity 100%

–Specificity > 99.5%

• Tests for individual diagnosis

–Sensitivity > 99.5%

–Specificity > 99%

Sensitivity and Specificity of HIV tests

• Diagnostic Sensitivity

–The ability of the test to identify

correctly those who have the disease

• Diagnostic Specificity

–The ability of the test to identify

correctly those who do not have the disease

Sensitivity & Specificity

Test Parameter

Interpreting HIV Test Results

Assay 1 Assay 2 Assays 1+2 (in sequence)

Sensitivity 99.0% 99.0%

Specificity 99.5% 99.9%

Prevalence PPV PPV PPV

0.2% 28.4% 66.4% 99.75%

2.0% 80.2% 80.2% 99.97%

20.0% 98.0% 99.6% 99.99%

PPV & Prevalence

Sensitivity = 99.5%, Specificity = 99%PPV = 81.59/180.77 = 45.135%

NPV = 9,818.82/9,819.23 = >99.99%

HIV

InfectionNo HIV Infection

Positive results

81.59 99.18 180.77

Negative results

0.41 9,818.82 9,819.23

Prevalence0.82%

82 9,91810,000

(population)

PPV & NPV of HIV Testing

Prevalence(%)

%PPV:

1 test

%PPV:

2 tests

%PPV:

3 tests

%NPV

0.05 4.7415 83.2000 99.7975 99.9997

0.5 33.3333 98.0296 99.9798 99.9975

0.82 45.1347 98.7930 99.9877 99.9958

2.0 67.0034 99.5075 99.9950 99.9897

5.0 83.9662 99.8085 99.9981 99.9734

10.0 91.7051 99.9092 99.9991 99.9439

PPV and NPV of HIV Testing Strategies at Different Prevalence Rates

• UNAIDS and WHO Recommended Alternative HIV

Testing Strategies (1997)

• Thailand HIV Testing Algorithms (2013)

• CDC Laboratory testing for the Diagnosis of HIV

Infection: Updated Recommendation (2014)

• WHO New Guidelines on HIV Testing (2015)

• Thailand Update Guideline for HIV Testing (2016)

HIV Testing Strategies/Algorithms

http://thaiaidssociety.org/index.php?option=com_content&view=article&id=79&Itemid=86

Tests for individual diagnosis

– Sensitivity > 99.5%– Specificity > 99%

Thailand HIV testing algorithm for individual diagnosis (2013)

Anti-HIV negative

A1+ (R)

A2

Repeat A1 and A2

A1+, A2+

A1+, A2+, A3+

Anti-HIV PositiveRetest sample 2

Inconclusive

A1+, A2+, A3-

Retest at 2 weeks and/or 1 month and 3 months

A1

A3

A1-, A2-

A1+, A2- A1+, A2+

A1+, A2-

A1- (NR)

HIV testing Algorithms in Adults and Children >18 M

HIV testing Algorithms in Children <18 M

http://www.cdc.gov/hiv/pdf/HIVtestingAlgorithmRecommendation-Final.pdf

Published June 27, 2014

Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens

• More accurate laboratory diagnosis of acute HIV-1 infection,

• Equally accurate laboratory diagnosis of established HIV-1 infection,

• more accurate laboratory diagnosis of HIV-2 infection,

• fewer indeterminate results, and

• Faster turnaround time for most test results.

The recommended algorithm has several advantages

http://www.who.int/hiv/en/

WHO New Guidelines on HIV Testing (2015)

http://apps.who.int/iris/bitstream/10665/179870/1/9789241508926_eng.pdf?ua=1&ua=1

HIV inconclusive 1. A1+A2-A3+ or2. A1+A2-A3-If A1 is 4th gen assay

Retest in 14 days

Testing strategy for HIV diagnosis in high prevalence settings (≥ 5%)

HIV inconclusive 1. A1+A2+A3- or2. A1+A2-If A1 is 4th gen assay

Retest in 14 days

Testing strategy for HIV diagnosis in low prevalence settings (<5%)

WHO recommends retesting to assure

accurate diagnosis in three instances:

1. retesting people who test HIV-negative but

are at on-going risk for HIV;

2. retesting people with an HIV inconclusive

status after 14 days; and

3. retesting to verify an HIV-positive diagnosis

before enrolling in care and/or starting antiretroviral therapy (ART)

When to retest?

?

Thailand Update Guideline for HIV Testing (2016)

Inconclusive: Retest at 2 weeks and 1 month

HIV testing Algorithms in Adults and Children >24 Months

HIV testing Algorithms in Children <24 Months

No diagnostic test or algorithm can be completely accurate in

all cases of HIV infection.