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.