Diagnosing HIV using rapid screening test may not be reliable in HIV-1 controllers, a rare group of individuals living with HIV who maintain HIV viremia at extremely low or even undetectable levels in the absence of antiretroviral treatment, according to a brief report published in Clinical Infectious Diseases.

Researchers used data of 85 patients who were identified as HIV controllers and were enrolled in the ongoing ANRS CODEX (Agence Nationale de Recherches sur le SIDA et les hépatites virales CO21 Cohorte des Extrêmes) from 2009 to 2017 to evaluate the risk for false-negative results contributing to HIV misdiagnoses. Researchers investigated anti-HIV humoral antibody detection and its evolution in this cohort, all of whom had HIV RNA plasma loads <100 copies/mL for longer than 5 years except during the diagnosis.

A highly sensitive and specific HIV rapid screening test, 2 fourth-generation HIV enzyme immunoassays, and an HIV-1 Western blot confirmation assay were performed on the first frozen plasma samples available at the time of inclusion in the study cohort and, if sufficient plasma was available, these tests were also performed on the last sample collected in the cohort with an undetectable viral load.

HIV RNA was quantified in a large volume of frozen plasma every 12 months by ultrasensitive quantitative reverse-transcription polymerase chain reaction. HIV DNA was quantified in frozen peripheral blood mononuclear cells by ultrasensitive polymerase chain reaction.

The median and range of the number of ultrasensitive HIV RNA tests performed during the observation period were 5. Only 1 participant who was categorized as an HIV controller had HIV RNA consistently <100 copies/mL but never undetectable, with the highest HIV RNA at 33 copies/mL.

The rapid screening test was negative in 4% cases. The 2 fourth-generation HIV enzyme immunoassays tests (bioMérieux and Abbott assay) were positive in the first serum sample of all tested participants with results that were sometimes near the positivity cutoff threshold. Overall, Western blots were positive in 94% of cases and indeterminate in 6% of cases.

To investigate a possible decline in HIV antibodies associated with viral load control, researchers examined the variation over time for 65 participants who were HIV controllers who had available plasma at a second collection time point and who had a median follow-up of 3.2 years after inclusion in the cohort. Rapid screening test results were stably positive for 61 of 64 participants who were HIV controllers. The HIV enzyme immunoassays remained positive for all participants who were HIV controllers. While 92% of HIV controllers (60/65) had no change in the Western blot pattern, 3 participants lost HIV-1 antibodies, and 2 participants had 1 additional detectable antibody.

Combining the results of 2 points of analysis, 6% of participants who were HIV controllers had a negative rapid screening test and 7% had an indeterminate Western blot.

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“Our results show that the [rapid screening test] may not be reliable in the context of natural control and very low immune stimulation over a period of several years,” noted the researchers. “HIV diagnosis in [HIV controllers] can be difficult, and quantification of HIV DNA with ultrasensitive assays is sometimes needed to definitively confirm infection,” they concluded.

Disclosure: Olivier Lambotte and Véronique Avettand-Fenoel declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of their disclosures.

Reference

Hage-Sleiman M, Tremeaux P, Fillion M, et al; CODEX ANRS Cohort Study Group. False-negative results of human immunodeficiency virus (HIV) rapid testing in HIV controllers [published online September 21, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz734