Managing Acute HIV Infection

Nucleic Acid Amplification Testing January 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.

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

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Period of acute infection associated with high viral load.

Setting the Stage

• ~ 6,400 new cases of HIV reported in Texas in 2007.

• 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 APTIMA



of the HIV-1 Assay in a High Risk Population

Gen-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

Acute HIV ARS* Established Infection RNA NAAT p24 4 th gen EIA 2 nd & 3 rd gen EIA Western Blot Less Sensitive EIA 2 7 Days 14 3 4 Weeks 5 24 CD4 HIV Abs Viremia Genital Shedding *Acute Retroviral Syndrome After Pilcher, 2008

Detection Range of HIV Tests

ACUTE SYMPTOMS HIV-1 RNA NAAT (2006) HIV EIA 1 ST (1985) & 2 ND (1997-98) Generation HIV EIA 3 RD (~2002-2003) Generation Western Blot (1985)

1 2 3 4 5 6

Weeks After Infection

7

NAAT Testing of Pooled Sera to Identify Acute HIV Infection (seronegative, NAAT positive) Program

Pooled HIV RNA Testing: Yields New York City

Population

NYC 3 STD Clinics

Prevalence HIV RNA+/EIA Increase in Testing Yield

15% North Carolina All persons tested for HIV via North Carolina DOH 23/109,250 (0.02%) 4% Public-Health Seattle & King County San Francisco Men who have sex with men tested through PHSKC SF STD Clinic Patients 21/5995 (0.35%) 11/2722 (0.40%) 13.5% 10.5% Los Angeles Men tested in 3 STD Clinics 1/1698 (0.06%) 7.1% Maryland (not Baltimore) Atlanta STD clinics 0/15000 0 STD clinics, community testing and drug treatment STD clinic 4/2128 (0.19%) 5% Washington DC 6/1553 (0.39%) 10%

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

May 5, 2005

Pooling and HIV RNA testing

90 individual HIV antibody negative or WB indeterminate specimens 1 2 3 4 5 6 7 8 9 10 A B C D E F G H I 9 intermediate pools (10 specimens) A B C D E F G H I 1 master pool (90 specimens) A B C D E F G H I A B C D E F G H I

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.