Higher risk of false-positive HIV test in those testing positive for COVID-19 infection

Having a positive SARS-CoV-2 polymerase chain reaction (PCR) test was significantly associated with false-positive fourth-generation HIV test results in a recent retrospective study.

Researchers measured false-positive rates of laboratory-based fourth-generation HIV antigen/antibody tests among patients who underwent PCR testing for SARS-CoV-2 within two weeks of HIV testing from March 2020 to January 2022 at one U.S. hospital. The researchers reviewed and categorized HIV assays as false positive, true positive, and presumptive negative. Results were published May 9 by Clinical Infectious Diseases.

A total of 31,910 medical records met the study criteria, with 31,575 patients having a presumptive negative HIV test result, 248 having a true positive, and 87 having a false positive. The rate of positive COVID-19 test results was highest among those with false-positive HIV tests at 19.5%, a significant difference compared to those with presumptive negative results (11.3%; P=0.016) and true-positive results (7.7%; P=0.002). Among false-positive patients with active COVID-19 infection, the mean age was 45.6 years, 52.9% were female, 70.6% were Black, 17.7% were White, and 94.1% were not immunized against SARS-CoV-2.

After adjustment for variables including age, race, ethnicity, gender, pregnancy, and COVID-19 immunization status, a false-positive HIV test was significantly associated with COVID-19 (odds ratio, 4.22 [95% CI, 1.84 to 9.67]; P=0.001). This remained true after excluding pregnant patients (odds ratio, 4.07 [95% CI, 1.76 to 9.42]; P=0.001). A logistic regression analysis to predict a false-positive HIV test found that a false-positive HIV test result was 2.93 times more likely to occur in those with COVID-19 compared with those without (odds ratio, 2.93 [95% CI, 1.44 to 5.94]; P=0.003). The median interval between the 17 positive SARS-CoV-2 PCR and false-positive HIV tests was 0.98 day (range, 0.09 to 13.84 days).

“The exact biochemistry of falsely reactive tests is often unknown and attributed to a ‘general’ inflammatory process, to which COVID-19 is no stranger,” the study authors wrote. “While we were unable to link the degree of inflammation to false HIV positivity, we were able to show that HIV Ag reactivity was a primary trigger for [a false-positive] result on the test used in this study.”

Limitations of the study include its retrospective design and the fact that those with presumptive negative HIV results did not undergo viral load testing unless acute HIV infection was suspected, the authors noted. They added that the results are confined to those with PCR-positive COVID-19 and that only one platform was used for HIV and COVID-19 testing, which limits generalizability. “In conclusion, acute COVID-19 should be considered as a potential etiology for [a false-positive] fourth-generation HIV test,” they wrote.