Advances in HIV serology: Implications for clinical care

The detection of both established and acute HIV infection (AHI) is important for reducing HIV transmission. AHI is associated with very high viral loads, and the magnitude of the viral load correlates with the transmission risk

The detection of both established and acute HIV infection (AHI) is important for reducing HIV transmission. AHI is associated with very high viral loads, and the magnitude of the viral load correlates with the transmission risk. Detecting AHI is particularly important because acute infections account for 10% to 50% of transmission events.[1,2] In addition to the use of safe sexual practices, control of HIV transmission requires timely diagnosis, engagement into care, and rapid initiation of antiretroviral therapy to decrease HIV RNA levels to reduce transmission.[3,4]  

Immediately after HIV infection there is an eclipse period, lasting about 10 days, where no HIV markers are detectable in blood.[5] Approximately 10 days after infection, HIV RNA becomes detectable and the viral load increases during the ensuing weeks. HIV p24 antigen and HIV antibodies can be detected about 18 days after infection by fourth-generation immunoassays. These modern HIV p24 antigen/antibody assays, which are used throughout BC for HIV screening, detect infections about 4 to 5 days earlier than the older, third-generation assays that only detected HIV antibodies. Specimens reactive by fourth-generation immunoassays are automatically tested to determine if the HIV infection is acute or established. AHI cases have detectable HIV RNA and negative or indeterminate immunoblot results. 

Since 2009, the BC Centre for Disease Control Public Health Laboratory (BCCDC PHL), which performs most of the HIV screening and confirmatory testing in BC, has also been using pooled HIV RNA nucleic acid testing (NAT) as a strategy to identify AHI in very high-risk populations.[6] The BCCDC PHL also performs a limited number of HIV NAT tests to detect AHI in high-risk seronegative prenatal women and their neonates. In 2015, the BCCDC PHL switched to a fourth-generation immunoassay from third-generation, and in 2016 replaced the traditional HIV-1 specific Western blot with a rapid immuno-blot that differentiates between HIV-1 and -2 antibodies. The BCCDC PHL has demonstrated that use of a fourth-generation immunoassay reduces the test-negative window and improves the sensitivity for AHI detection relative to the older third-generation immunoassays. Pooled and individual NAT identified 37% (19/51) of AHI cases during a 15-month period when third-generation immunoassay screening was used (February 2014 to May 2015), while only 10% (6/61) of AHI cases were identified using NAT during a subsequent 15-month period when fourth-generation immunoassay screening was used (June 2015 to August 2016). Therefore, the utility of NAT for AHI diagnosis is significantly reduced when fourth-generation EIA is used as the primary HIV screening test.

Physicians should only request NAT testing from:
High-risk prenatal women and their neonates.
High-risk men who have sex with men (pooled NAT).
Patients with suspected acute HIV.

—Agatha Jassem, PhD, D(ABMM), FCCM
—Mel Krajden, MD, FRCPC


This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.


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Agatha Jassem, PhD, (D)ABMM, FCCM, Mel Krajden, OBC, MD, FRCPC. Advances in HIV serology: Implications for clinical care. BCMJ, Vol. 59, No. 10, December, 2017, Page(s) 499 - BC Centre for Disease Control.

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