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HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes

HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes

Test Summary

HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes

  

Clinical Use

  • Screen for and confirm HIV-1/HIV-2 infection, including acute HIV-1 infection

  • Differentiate HIV-1 from HIV-2 infection

Clinical Background

More than 1.1 million people in the United States were living with HIV infection as of 2014, 15% of whom did not know they were infected.1 Another 37,600 individuals are newly infected each year.1 Identification and treatment of HIV infection can lead to substantial benefits in terms of decreased transmission, morbidity, and death.2 The US Preventive Services Task Force thus recommends voluntary, opt-out, screening for all pregnant women and for individuals 15 to 65 years of age in regions where the prevalence of infection is ≥0.1%. Individual risk assessments determine the need for screening beyond this age range.2 The importance of detecting HIV during the acute phase (before seroconversion) is increasingly recognized; the acute phase is marked by high viral load and appears to contribute disproportionately to transmission.3

The conventional HIV testing algorithm begins with a "third-generation" HIV-1/HIV-2 antibody immunoassay, followed by supplemental testing (eg, Western blot) to confirm repeatedly reactive results. This approach is highly sensitive and specific but has several drawbacks: it cannot detect acute infection; it does not readily differentiate between HIV-1 and HIV-2; and negative or indeterminate results on Western blots during early seroconversion can delay diagnosis. An alternative algorithm proposed by the CDC4 and adopted by the Clinical Laboratory Standards Institute (CLSI)5 is designed to avoid these drawbacks.

The alternative algorithm begins with (preferably) a "fourth-generation" combination assay that detects HIV p24 antigen in addition to HIV antibodies. Because HIV p24 antigen is detectable before seroconversion, fourth-generation assays can detect HIV-1 during acute infection; the inclusion of HIV-1 and HIV-2 antibodies allows detection after seroconversion, when p24 antigen becomes undetectable. Fourth-generation assays have >99.7% sensitivity and >99.3% specificity for HIV infection and can identify most (>80%) acute infections that would otherwise require nucleic acid testing for detection.6,7 In general, they can detect infection 0 to 20 days (median, 5-7 days) before third-generation immunoassays.5,8,9

Repeatedly reactive results on fourth-generation screening tests require confirmation with a supplemental test, such as an HIV-1/HIV-2 antibody differentiation assay. Differentiation between HIV-1 and HIV-2 antibodies can have treatment implications, as HIV-2 does not respond to some antiretroviral agents. Differentiation tests also tend to detect antibodies earlier than Western blots.10 But like Western blots, HIV-1/HIV-2 antibody differentiation tests do not detect acute infection. HIV RNA testing is thus needed to resolve infection status in patients with positive results on the fourth-generation assay but negative results on the antibody differentiation test.

Quest Diagnostics has collaborated with the CDC on key clinical studies supporting the alternative algorithm,6,10-12 which has demonstrated high sensitivity (>99.7%) and specificity (100%).12,13 The HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes assay (Figure) is consistent with this algorithm.

Figure. Reflex Pathway for the HIV-1/2 Antigen and Antibodies, Fourth Generation, with Reflexes Assay (91431)

Individuals Suitable for Testing

  • Pregnant women

  • Adolescents and adults 15 to 65 years of age, and beyond this range for those at increased risk

  • Individuals with recent confirmed or suspected exposure to HIV-1 or HIV-2 infection

  • Children 2 years of age or older with suspected HIV infection

Method

  • Chemiluminescent microparticle immunoassay specific for

   HIV p24 antigen

   HIV-1 (groups M and O) and HIV-2 antibodies

  • Repeatedly reactive screening results are reflexed to the supplemental HIV-1/2 antibody differentiation test; nonreactive or indeterminate HIV-1/2 antibody differentiation results are reflexed to the HIV-1 Qualitative RNA, TMA test. See Figure for reflex pathway and reporting.

Reference Range

Nonreactive

Interpretive Information

Interpretative information for the reflex pathway is depicted in the Figure.

References

  1. Centers for Disease Control and Prevention. HIV/AIDS: Statistics overview. http://www.cdc.gov/hiv/statistics/
    basics/
    . Accessed June 29, 2015.

  2. Moyer VA, U.S. Preventive Services Task Force. Screening for HIV: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159:51-60.

  3. Detection of acute HIV infection in two evaluations of a new HIV diagnostic testing algorithm - United States, 2011-2013. MMWR Morb Mortal Wkly Rep. 2013;62:489-494.

  4. Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory testing for the diagnosis of HIV infection: updated recommendations. http://stacks.cdc.gov/view/cdc/23447. Published June 27, 2014. Accessed October 22, 2015.

  5. CLSI. Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus Infection; Approved Guideline. M53-A ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2011.

  6. Nasrullah M, Wesolowski LG, Meyer WA, III, et al. Performance of a fourth-generation HIV screening assay and an alternative HIV diagnostic testing algorithm. AIDS. 2013;27:731-737.

  7. Chavez P, Wesolowski L, Patel P, et al. Evaluation of the performance of the Abbott ARCHITECT HIV Ag/Ab Combo Assay. J Clin Virol. 2011;52 (suppl 1):S51-S55.

  8. Fiebig EW, Wright DJ, Rawal BD, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS. 2003;17:1871-1879.

  9. ARCHITECT HIV Ag/Ab Combo [package insert]. Wiesbaden, Germany: Abbott Laboratories; 2009.

  10. Wesolowski LG, Delaney KP, Meyer WA, III, et al. Use of rapid HIV assays as supplemental tests in specimens with repeatedly reactive screening immunoassay results not confirmed by HIV-1 Western blot. J Clin Virol. 2013;58:240-244.

  11. Delaney KP, Heffelfinger JD, Wesolowski LG, et al. Performance of an alternative laboratory-based algorithm for HIV diagnosis in a high-risk population. J Clin Virol. 2011;52 (suppl 1):S5-10.

  12. Wesolowski LG, Delaney KP, Hart C, et al. Performance of an alternative laboratory-based algorithm for diagnosis of HIV infection utilizing a third generation immunoassay, a rapid HIV-1/HIV-2 differentiation test and a DNA or RNA-based nucleic acid amplification test in persons with established HIV-1 infection and blood donors. J Clin Virol. 2011;52 (suppl 1):S45-S49.

  13. Masciotra S, McDougal JS, Feldman J, et al. Evaluation of an alternative HIV diagnostic algorithm using specimens from seroconversion panels and persons with established HIV infections. J Clin Virol. 2011;52(suppl 1):S17-S22.
     

Reflex tests are performed at additional cost and are associated with additional CPT code(s).

 Content reviewed 9/2017
 

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