Real-world performance of HIV low viral load values in diagnosing acute HIV infection in a tertiary care hospital in Beijing, China – BMC Infectious Diseases

In this study, we analyzed the viral load and confirmatory antibody results at Beijing Youan Hospital from 2019 to 2022. We found that of 2434 patients had both confirmatory antibody results and viral load results, 140 individuals (5.8%) had viral load values ranging from 40 copies/mL to 5000 copies/mL before positive confirmatory antibody results, and of these 140 patients, the sample receipt time for the viral load test of 96(66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, the viral loads of 34 patients (1.4%) ranged from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody results were obtained.

Abbott RealTime HIV-1 Assay are recommended for HIV-1 RNA monitoring and are not intended for diagnosis of infection. HIV-1 RNA qualitative assays are recommended for diagnosis of infection, but they are not used in the clinical setting in China. HIV-1 RNA quantification diagnostics, such as Abbott RealTime HIV-1 Assay, are being widely used in clinical setting in China. Society of Infectious Diseases Chinese Medical Association and Chinese Center for Disease Control and Prevention has established guidelines for the use of existing quantitative HIV-1 RNA diagnostics for the diagnosis of HIV-1 infection, the proposed threshold is 5,000 copies/mL. According to the US Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, in the presence of compatible symptoms or exposure history, a low HIV RNA concentration is consistent with acute HIV infection, the previously proposed threshold is 3,000 copies/ mL [7]. According to the 2021 European guideline on HIV testing in genito-urinary medicine settings, low HIV RNA concentrations (8]. The incorporation of nucleic acid amplification testing into HIV testing is beneficial for diagnosing acute HIV infection and decreasing HIV transmission [9]. In this study, 140 individuals (5.8%) had viral loads raging from 40 copies/mL to 5000 copies/mL before positive confirmatory antibody results, which indicated a risk of missed diagnosis if a threshold of 5000 copies/mL was used for the diagnosis of HIV infection in China. Our findings provide valuable information for the early diagnosis of HIV infection.

HIV RNA and the p24 antigen can be detected approximately 11 to 12 days and 14 to 15 days after infection respectively, and HIV specific antibodies can be detected three to eight weeks after infection [10]. Because HIV specific antibodies appear later than HIV RNA in the blood after infection, one or more HIV viral load tests were done before a positive confirmatory antibody result for high-risk groups. In this study, the viral load values ranging from 40 copies/mL to 5,000 copies/mL of 96 (66.7%) individuals were detected 1 to 6 days earlier than a positive confirmatory antibody result. To diagnose acute HIV-1 infection earlier, more HIV viral load tests should be considered before a positive confirmatory antibody result for the time interval between HIV RNA and HIV specific antibodies appearance. Of the 795 outpatients with HIV-seronegative/HIV-serodiscordant results, 30 patients (3.8%) were diagnosed with acute or early HIV infection after undergoing diagnostic testing with the quantitative Xpert HIV-1 viral load assay [11]. Compared with the fourth-generation HIV antigen/antibody test, the number of acute infected patients increased from 81 to 112 after the addition of pooled nucleic acid testing [12]. A total of 467 HIV antibody-negative samples were tested by HIV pooled nucleic acid testing (Roche Molecular Systems), four (0.9%) of which were HIV-1 RNA positive [13]. In the present study, individuals with low viral loads were identified before positive antibody confirmatory results were obtained.

To investigate the impact of low HIV viral load on HIV diagnosis, contamination during HIV viral load testing must be eliminated. The increased automation of HIV viral load testing reduces cross-contamination and biosafety risks. Pilcher et al. reported two false positive results from nucleic acid amplification tests, these two patients had positive nucleic acid test results at initial testing, but negative results from both nucleic acid amplification and antibody testing at follow-up [14]. As a supplementary HIV testing strategy, the sensitivity and specificity of the reagent should be improved to avoid or reduce the occurrence of false-positive results [15]. Following CAR-T cell therapy, several false positive HIV nucleic acid tests have been reported, and there are cross reactions between lentiviral vectors and HIV genomes targeted in the HIV viral load assays; these false positive results may be related to the use of lentiviral vector [16, 17]. Low HIV RNA concentrations (e.g.,

In this study, a retrospective analysis was conducted of patients who underwent HIV confirmatory antibody tests and HIV viral load tests at Beijing Youan Hospital from 2019 to 2022. This was a cross-sectional study, and only a few patients had two or more follow-up results. To investigate the impact of low HIV viral load on HIV diagnosis, it is better to establish a prospective cohort and conduct routine follow-up of enrolled patients [18].

In conclusion, the confirmatory antibody results and viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis, and 140 patients (5.8%) had viral load values ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody results. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.