Failure to Identify HIV-Infected Individuals in a Clinical Trial Using a Single HIV Rapid Test for Screening

Abstract

Background In the HIV Prevention Trials Network (HPTN) 061 study, 8 (2.3%) of 348 HIV-infected participants identified as HIV uninfected at study enrollment using a single HIV rapid test for screening were found to be HIV infected after additional testing. Objectives To evaluate the performance of different HIV assays for detection of HIV infection in HPTN 061 participants with missed infection and individuals with viral suppression. Methods Plasma samples from 8 HPTN 061 participants, 17 elite controllers, and 101 individuals on antiretroviral treatment (ART) were tested for HIV with 3 rapid tests, 2 laboratory-based immunoassays, and a Western blot assay. The HPTN 061 samples were also tested with 2 HIV RNA assays and an antiretroviral drug assay. Results Of the 8 HPTN 061 participants with missed infection, 1 was an elite controller, 1 was taking ART, 2 were missed because of testing or clerical errors, 1 had recent HIV infection (identified using a multi-assay algorithm), and 3 had acute HIV infection. Two (1.7%) of 118 individuals with viral suppression (both taking ART) had at least 1 false-negative test. Conclusions In clinical trials, HIV infections can be missed for a variety of reasons. Using more than one assay to screen for HIV infection may reduce the number of missed infections.

Infrequent HIV Testing and Late HIV Diagnosis Are Common Among a Cohort of Black Men Who Have Sex With Men in 6 US Cities

“…In eight cases, CD4 cell count testing was not performed because the initial HIV rapid test was non-reactive; those men (including three with acute HIV infection) were retrospectively identified as HIV-infected at the HPTN Laboratory Center. 60 The median CD4 cell count for the 84 men was 404 cells/mm 3 (interquartile range [IQR]: 209, 581); 33 (39.3%) had a CD4 cell count <350 cells/mm 3 at enrollment, including 17 (20.2%) who had a CD4 cell count <200 cells/mm 3 . In a univariate analysis of correlates of late testing, only age over 30 years was associated with late diagnosis using the definition of CD4 cell count <350 cells/mm 3 (47.4% vs. 22.2%; p<0.05).…”

Low-Level Viremia Early in HIV Infection

“…In a previous report, we described two other cases from the HPTN 061 study where HIV infection was missed at all three study visits when a single HIV rapid test was used for screening at study sites; one of those men was likely an elite controller, and the other was virally suppressed on ART. 10 In one case, HIV infection was also missed using other HIV rapid tests and the Abbott Combo assay. Taken together, our findings indicate that low-level viremia in early HIV infection should be considered when HIV RNA assays are included in algorithms for HIV diagnosis.…”

“…7 Viral suppression has also been associated with false-negative results using serologic HIV assays. 8-10 In this report, we describe six individuals who acquired HIV infection during a clinical study and had low or undetectable HIV RNA at their first HIV-positive study visit.…”

Determination of HIV Status in African Adults With Discordant HIV Rapid Tests

“…Elite controllers may not be aware of their HIV status and may be incorrectly classified as HIV-uninfected because of false-negative HIV tests. 33 Viral suppression may also complicate identification of newly-infected individuals. We recently described a cohort in the US in which 21% of HIV seroconverters had low or undetectable HIV RNA in the absence of antiretroviral drug use.…”

“…17 In the same study, HIV infection was missed at multiple visits in two virally-suppressed participants using an HIV rapid test; in one case, HIV infection was also missed using a fourth-generation assay. 33 Missed HIV infection may become more common in resource-limited settings that rely on third-generation HIV screening assays and simple HIV testing algorithms, particularly as ART is scaled up for HIV treatment and prevention. 34–36 …”