HIV 1/2 ANTIGEN/ANTIBODY,FOURTH GENERATION W/RFL

"Clinical Use

Screen for and confirm diagnosis of HIV-1/HIV-2 infection, including acute HIV-1 infection
Differentiate HIV-1 from HIV-2 infection

Clinical Background

An estimated 1.1 million people in the United States were living with HIV infection in 2016; about 14%—or 1 in 7—did not know they were infected.1 Another 37,832 people were newly infected in 2018.1 Identification and treatment of patients with 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 HIV screening for all pregnant women and for persons 15 to 65 years of age.2 Individual risk assessments determine the need for screening persons under 15 years of age or older than 65 years of age.2 The importance of detecting HIV infection in patients 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 Centers for Disease Control and Prevention (CDC) recommends an HIV diagnostic testing algorithm that is based on a fourth-generation combination assay.4,5 The Clinical Laboratory Standards Institute (CLSI) has adopted this algorithm to avoid the drawbacks of earlier generations of HIV diagnostic tests.6 The current algorithm begins with 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 1 to 20 days (median, 5-7 days) before third-generation immunoassays.6-8

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. HIV-1/HIV-2 antibody differentiation assays also tend to detect antibodies earlier than previously employed antibody confirmation methods (eg, Western blots).7 But, like Western blots, HIV-1/HIV-2 antibody differentiation assays do not detect acute infection. HIV RNA testing is thus needed to resolve infection status in patients with positive results on the fourth-generation test but negative results on the antibody differentiation assay.7

Quest Diagnostics has collaborated with the CDC on key clinical studies supporting the current algorithm,9-12 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, including those who are in labor or delivery
Adolescents and adults 15 to 65 years of age
Individuals under 15 years of age or older than 65 years of age who are at increased risk of HIV infection
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
Specimens with repeatedly reactive screening results are reflexed to the supplemental HIV-1/2 antibody differentiation test; specimens with 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.

Interpretive Information

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

Includes
If HIV Antigen and Antibody, 4th Generation Screen is Repeatedly Reactive, then HIV-1/2 Antibody Differentiation will be performed at an additional charge (CPT code(s): 86701, 86702).
If HIV-1/2 Antibody Differentiation is Indeterminate or Negative, then HIV-1 RNA, Qualitative Real-Time PCR will be performed at an additional charge (CPT code(s): 87535).

Methodology
Immunoassay (IA)

Reference Range(s)
HIV Ag/Ab, 4th Generation    Non-Reactive

Alternative Name(s)
Fourth Generation HIV,4th Generation HIV