1 Managing Acute HIV Infection Nucleic Acid Amplification Testing January 26, 2009 Nick Curry, MD, MPHInfectious Diseases Prevention SectionTexas Department of State Health Services
2 Setting the StageIn 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.
3 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.
4 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 detectedORWindow period when routine HIV antibody tests (EIAs) are negative but HIV can be detected in blood
5 What is the Rationale for Detecting Acute Infection? Interruption of HIV Transmission From Highly Infectious Individuals using NAAT and rapid DIS responseImproved HIV Infection DiagnosisEarlier and Appropriate Clinical Management of Acutely Infected PersonsEnhanced HIV SurveillanceImproved Assessment of Epidemiologic Trends
6 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.
7 Clinical Genetic Amplification for HIV Nucleic Acid Amplified Test (NAAT) ExamplesOnly one FDA approved diagnostic testTranscription Mediated Amplification (TMA) - APTIMA® HIV-1 RNA Qualitative Assay by GenProbe (2006)Specificity and sensitivity 100% in high-risk 100 copies/mlEarliest possible detection of infectionDetects all major groups of HIV-1Turnaround 3-7 days
8 Diagnostic Nucleic Acid Amplification for HIV Transcription Mediated Amplification (TMA) – Uses RNA Polymerase and Reverse Transcriptase; can amplify RNA or DNA targets; isothermal
9 Clinical Sensitivity and Specificity of the APTIMA HIV-1 Assay in a High Risk Population Gen-Probe
10 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.”
11 Intended UseIt 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 infectionsMay 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 antibodiesGen-Probe
12 Established Infection Acute HIVEstablished InfectionRNA NAATp244th gen EIA2nd & 3rd gen EIAWestern BlotLess Sensitive EIAARS*CD4HIV AbsViremiaGenital Shedding271434524*Acute Retroviral SyndromeDaysWeeksAfter Pilcher, 2008
13 Detection Range of HIV Tests ACUTESYMPTOMSHIV-1 RNA NAAT (2006)HIV EIA 1ST (1985) & 2ND ( ) GenerationHIV EIA 3RD (~ ) GenerationWestern Blot (1985)1234567Weeks After Infection
14 NAAT Testing of Pooled Sera to Identify Acute HIV Infection (seronegative, NAAT positive) After Leone, from International Society for Sexually Transmitted Disease Research, 200714
16 Pooling and HIV RNA testing A B C D E F G H I90 individual HIV antibody negative or WB indeterminate specimens9 intermediate pools (10 specimens)1 master pool (90 specimens)
17 North Carolina New NAAT Assay and Pooling Algorithm GenProbe APTIMA HIV-1 RNA NAAT assayHamilton STARlet robotic pipetting instrumentReduced pool size (80 samples/pool)Increased sensitivity for HIV-1 NAATMyra Brinson - North Carolina Laboratory of Public Health, 2008
18 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^Perform both screening and diagnostic assays*Will begin diagnostic assays in 2009**Will request funding to begin diagnostic assay in 2009.@Perform screening assays
19 A sexual network presented by Lisa Hightow at CROI in 2006 A sexual network presented by Lisa Hightow at CROI in This demonstrates the large numbers of sexual partners an acute case may have and the increasing use of the Internet to acquire new sexual partners. Identifying acutely infected individuals, counseling them, enrolling them in medical care, and interrupting disease transmission are key objectives associated with the use of Nucleic Acid Amplification Testing.
20 HIV-1 NAAT SummaryHIV-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.