Managing Acute HIV Infection Nucleic Acid Amplification Testing January 26, 2009 Nick Curry, MD, MPH...

Managing Acute HIV Infection

Nucleic Acid Amplification TestingJanuary 26, 2009

Nick Curry, MD, MPH

Infectious Diseases Prevention Section

Texas Department of State Health Services

Setting the Stage

• In Texas, >25% of those initially diagnosed as HIV-infected, receive a diagnosis of AIDS within one month of the HIV diagnosis.

• Several studies have demonstrated that fifty percent or more of HIV transmission is due to acutely infected sources.

• Period of acute infection associated with high viral load.

Setting the Stage• ~ 4,600 new cases of HIV reported in

Texas in 2006.

• Black females are nineteen times more likely to be diagnosed with HIV when compared to white females today.

• Black males are five times more likely to be diagnosed with HIV when compared to white males.

Definition of Acute HIV Infection

• Time period following infection with HIV during which HIV can be detected in blood but antibodies to HIV are not detected

OR

• Window period when routine HIV antibody tests (EIAs) are negative but HIV can be detected in blood

What is the Rationale for Detecting Acute Infection?

• Interruption of HIV Transmission From Highly Infectious Individuals using NAAT and rapid DIS response

• Improved HIV Infection Diagnosis• Earlier and Appropriate Clinical

Management of Acutely Infected Persons• Enhanced HIV Surveillance• Improved Assessment of Epidemiologic

Trends

What is a nucleic acid amplification test?

• It is a test for the presence of HIV, not antibodies to HIV.

• It detects HIV infection before any antibody test can do so.

• It identifies the presence of HIV RNA, the nucleic acid which caries the HIV genetic information.

• It amplifies the HIV RNA for enhanced detection.• It is highly sensitive and specific.• It requires plasma (or serum) specimens.• It is approved as a diagnostic test, and can thus

replace the Western Blot for confirmation.

Clinical Genetic Amplification for HIV

• Nucleic Acid Amplified Test (NAAT) Examples– Only one FDA approved diagnostic test – Transcription Mediated Amplification (TMA) -

APTIMA® HIV-1 RNA Qualitative Assay by GenProbe (2006)

• Specificity and sensitivity 100% in high-risk populations @ 100 copies/ml

• Earliest possible detection of infection• Detects all major groups of HIV-1• Turnaround 3-7 days

Diagnostic Nucleic Acid Amplification for HIV

• Transcription Mediated Amplification (TMA) – Uses RNA Polymerase and Reverse Transcriptase; can amplify RNA or DNA targets; isothermal

Clinical Sensitivity and Specificity of the

APTIMA HIV-1 Assay in a High Risk Population

Gen-ProbeGen-Probe

Jay Epstein, M.D., Director, Office of Blood Research and Review, Center for

Biologics Evaluation and Research (CBER), FDA

• "This test also can detect infection with HIV-1 earlier than HIV antibody tests when used to detect primary HIV-1 infection.“

• “This test has important implications for medical diagnostic use because it could be a potential alternative to the traditional Western blot test now used for confirmation of HIV-1 infection when screening tests for HIV-1 antibodies are positive.”

Intended Use

• It is intended for use as an aid in the diagnosis of HIV-1 infection, including acute or primary infection. Presence of HIV-1 RNA in plasma of patients without antibodies to HIV-1 is indicative of acute or primary HIV-1 infections

• May also be used as an additional test, when it is reactive, to confirm HIV-1 infection in an individual whose specimen is repeatedly reactive for HIV-1 antibodies

Gen-Probe

2

Acute HIV Acute HIV

3 4 57 14 24

Established InfectionEstablished Infection

RNA NAATp244th gen EIA2nd & 3rd gen EIAWestern BlotLess Sensitive EIA

CD4HIV Abs

Viremia

Genital Shedding

ARS*

Days Weeks

*Acute Retroviral Syndrome

After Pilcher, 2008

Detection Range of HIV Tests

ACUTESYMPTOMS

HIV-1 RNA NAAT (2006)

HIV EIA 1ST (1985) & 2ND (1997-98) Generation

HIV EIA 3RD (~2002-2003) Generation

Western Blot (1985)

1 2 3 4 5 6 7Weeks After Infection

NAAT Testing of Pooled Sera to Identify Acute HIV Infection

(seronegative, NAAT positive)Pooled HIV RNA Testing: Yields

15%NYC 3 STD ClinicsNew York City

10%6/1553 (0.39%)STD clinicWashington DC

5%4/2128 (0.19%)STD clinics, community testing and drug treatment

Atlanta

00/15000STD clinicsMaryland (not Baltimore)

7.1%1/1698 (0.06%)Men tested in 3 STD ClinicsLos Angeles

10.5%11/2722 (0.40%)SF STD Clinic PatientsSan Francisco

13.5%21/5995 (0.35%)Men who have sex with men tested through PHSKC

Public-Health Seattle & King County

4%23/109,250 (0.02%)All persons tested for HIV via North Carolina DOH

North Carolina

Increase in Testing Yield

Prevalence HIV RNA+/EIA-

PopulationProgram

After Leone, from International Society for Sexually Transmitted Disease Research, 2007

May 5, 2005

Pooling and HIV RNA testing

A B C D E F G H I

1 2 3 4 5 6 7 8 9 10

A B C D E F G H I

A B C D E F G H I A B C D E F G H I

90 individual HIV antibody negative or WB indeterminate specimens

9 intermediate pools (10 specimens)

1 master pool (90 specimens)

North Carolina New NAAT Assay and Pooling Algorithm

• GenProbe APTIMA HIV-1 RNA NAAT assay

• Hamilton STARlet robotic pipetting instrument

• Reduced pool size (80 samples/pool)

• Increased sensitivity for HIV-1 NAAT

Myra Brinson - North Carolina Laboratory of Public Health, 2008

Who performs HIV RNA NAAT in Texas?

• Various private reference labs^• Dallas County Department of Health and

Human Services*• Houston Department of Health and Human

Services*• DSHS Laboratory**• Blood banks and organ donation centers@

^Perform both screening and diagnostic assays*Will begin diagnostic assays in 2009**Will request funding to begin diagnostic assay in 2009.@Perform screening assays

HIV-1 NAAT Summary• HIV-1 RNA NAAT can contribute to eliminating the

chain of HIV transmission.• HIV-1 RNA NAAT provides an option for early clinical

management of cases.• HIV-1 RNA NAAT will identify at least 2-3 acute

infections for every 10,000 specimens tested in high prevalence geographic areas.

• HIV-1 RNA NAAT expected to become a standard for HIV diagnosis within the next 2-3 years.

• HIV-1 RNA NAAT can replace the Western Blot as the confirmatory assay.