HIV Testing Past, Present and Future Mohammad Al-Ghoul, PhD, Technical Director Center for Disease Detection 03/31/2011
Objectives Advantages of using the fourth generation HIV assay Difference between the current and proposed testing algorithms Challenges with implementation of the fourth generation HIV assay
Percent of People that Reported Ever Being Tested for HIV 40% newly diagnosed HIV infected persons develop AIDS within one year of testing 50% of new sexually transmitted HIV infections are due to infected persons lack of awareness of infection. http://www.cdc.gov/vitalsigns/hivtesting/risk.html
Percent of People that Reported Ever Being Tested for HIV Percent CDC: Estimated 1.1 million people are living with HIV in the US and as many as 1 in 5 don t know they are infected http://www.cdc.gov/vitalsigns/hivtesting/risk.html
Screening everyone 13-64 years of age Screening everyone 13-64 years of age Elimination of written consent for HIV testing Annual testing of people with high risk factors Screening pregnant women in third trimester
National HIV/AIDS Plan Reduce infection HIV Better care Health Disparities Early detection of HIV infection
4 th Generation HIV Assay FDA-approved in June 2010 The first diagnostic assay: Detects HIV antibodies and HIV-1 p24 antigen Children 2 years May eliminate the need for WB testing Testing algorithm Ability to Detect HIV Infection Earlier
Testing Algorithim CDC/APHL -1989 : sequential two-test algorithm for diagnosis of HIV-1 infection Screening EIA Western Blot Immunofluorescence Assay (IFA)
Screening Assay s Sensitivity Compared to WB -20-15 -10-5 0 Days before western blot tests positive Some screening assays are more sensitive than WB
HIV Immunoassays Generation Mechanism window period First generation Viral lysate used to bind patient HIV Ab. Detects IgG antibody to HIV viral protein 4-12 weeks Second generation Same mechanism as first gen., but Use purified antigen or recombinant virus 4-12 weeks Third generation Same mechanism as gen. 1 and 2, but adds IgM detection 3-4 weeks Fourth generation Same mechanism as third gen, but in addition uses antibodies to detect p24 Ag in the patient serum 2 weeks Modified from Marqueez etal, MLO, 2008.
4 th Generation HIV Assay, Detect Infection in Acute Phase Acute retroviral symptoms HIV RNA HIV Abs 0-11 days, Infection Undetectable: No tests to close the gap 4 th generation improvement 11-22 days HIV p24 Ag 11 16 22 0 10 20 30 40 168 Viral Load by HIV RNA or other NAAT 50% of new HIV infections acquired from persons with AHI Modified from Patel et al, Arch Intern Med. 2010 4 th generation (p24 Ag+AbCombination) EIA HIV Antibody 3 rd gen HIV Antibody WB HIV Antibody 1 st and 2 nd gen
4 th Generation Assay vs. RNA Testing Study conducted by CDC RNA testing : 27 People with AHI 4 th gen: 23 People tested positive (85%) 4 People tested negative Patel et al, Arch Intern Med. 2010
Advantages of 4th Gen. Assay Detects HIV-1/-2 antibody and HIV-1 p24 antigen simultaneously Identifies HIV infection 2-20 days earlier than HIV antibody tests alone Detects acute, as well as latent infections using a time and cost-saving strategy.
Limitations of Current Algorithm CDC: Antibody tests do not detect infection in ~10% of infected persons at highest risk of transmission Early infection: Western blot is less sensitive than many widely used screening tests T-A-T reduce the effective sensitivity
Characteristics of an Ideal HIV Diagnostic Algorithm Detects HIV acute and latent infections Differentiates HIV-1 from HIV-2 Eliminates indeterminate results, and Reduces the diagnostic window
Proposed Testing Algorithm
Proposed Diagnostic Algorithm A1: 4 th generation HIV-1/2 immunoassay A1+ Repeat in duplicate A1(-) Negative for HIV-1 and HIV- 2 antibodies and p24 Ag A2: HIV-1/HIV-2 differentiation immunoassay HIV-1 + HIV-1 antibodies detected Initiate care (and viral load) Proposed in March 2010 CDC APHL HIV Diagnostic conference HIV-2 + HIV-2 antibodies detected Initiate care HIV-1&2 (-) RNA RNA+ RNA (-) Acute HIV-1 Negative for HIV-1 infection Initiate care
HIV-1/HIV-2 Discriminatory Test HIV-1 Reactive Preliminary Positive for HIV-1 antibodies Control HIV-2 Reactive: Preliminary Positive for HIV-2 antibodies HIV Reactive (Undifferentiated) the specimen may be tested by additional methods which allow for differentiation between HIV-1 and HIV-2 FDA: Result as presumptive positive http://www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/premarketapprovalspmas/ucm091384.pdf
Proposed Algorithm: Issues Validation is not complete Advancing the presumptive positive interpretation to a definitive positive Elimination of Western Blot Available resources Cost
Conclusion 4 th Gen assay : earlier detection of infection Proposed algorithm May eliminate WB May reduce indeterminate results Faster turn around of patient results If the new algorithm is recommended will you implement it in your laboratory?
Challenges with the Implementation of the 4 th Gen. Evidence Laboratory resources Clinician education
Thank You CDD: HIV Testing Team