Background
In clinical trials, discordant test results can complicate participant management and study endpoint determination. HIV diagnosis can be challenging when long-acting cabotegravir (CAB-LA) is used for HIV pre-exposure prophylaxis (PrEP) since HIV antigen, antibody, and RNA levels are often low. HIV assays can also revert from reactive/positive to non-reactive/negative in this setting. We evaluated a case where discrepant HIV test results were obtained for a participant receiving CAB-LA in the HIV Prevention Trials Network (HPTN) 083 trial.
Methods
The study site performed HIV rapid testing and antigen/antibody (Ag/Ab) testing; infections were confirmed with antibody and RNA tests. Retrospective testing was performed at the HPTN Laboratory Center using an Ag/Ab test, a discriminatory test, and an HIV RNA test. Plasma cabotegravir (CAB) was quantified via liquid chromatography-tandem mass spectrometry. Serologic ABO and Lewis testing was performed at the Johns Hopkins Hospital Transfusion Medicine Laboratory. Short tandem repeat DNA profiling was performed at the DNA Reference Laboratory using the Promega PowerPlex Fusion System and Promega PowerPlex Y23 System.
Results
The participant had 19 CAB-LA injections and then received 16 months of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) PrEP before enrolling in the open label extension of HPTN 083 (OLE). The participant received one CAB-LA injection in the OLE and then restarted TDF/FTC PrEP after an injection site reaction. All HIV test results, including an HIV RNA test, were negative/non-reactive at the first OLE visit; 26 days later, the HIV rapid test was non-reactive, the Ag/Ab test was reactive, the discriminatory test was positive, and the viral load was 2,588 copies/mL. All results at later visits were non-reactive/negative. Retrospective test results were consistent with the results from the study site. CAB concentrations were as expected based on the timing of injections. ABO groups, anti-A and anti-B titers, and Lewis phenotypes were the same for all samples tested. DNA profiling revealed that plasma from the visit with positive HIV test results was contaminated with DNA from an unrelated individual.
Conclusions
Detailed laboratory investigations may be required to explain unexpected or discrepant test results. In this case, DNA profiling explained the discrepant HIV test results, which helped guide clinical management of the study participant and excluded the case as a primary study endpoint.
Table or Figure
