Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients

Abstract

Context: Induction of protective anti-human immunodeficiency virus (HIV) immune responses is the goal of an HIV vaccine. However, this may cause a reactive result in routine HIV testing in the absence of HIV infection.

Objective: To evaluate the frequency of vaccine-induced seropositivity/reactivity (VISP) in HIV vaccine trial participants.

Design, setting, and participants: Three common US Food and Drug Administration-approved enzyme immunoassay (EIA) HIV antibody kits were used to determine VISP, and a routine diagnostic HIV algorithm was used to evaluate VISP frequency in healthy, HIV-seronegative adults who completed phase 1 (n = 25) and phase 2a (n = 2) vaccine trials conducted from 2000-2010 in the United States, South America, Thailand, and Africa.

Main outcome measure: Vaccine-induced seropositivity/reactivity, defined as reactive on 1 or more EIA tests and either Western blot-negative or Western blot-indeterminate/atypical positive (profile consistent with vaccine product) and HIV-1-negative by nucleic acid testing.

Results: Among 2176 participants free of HIV infection who received a vaccine product, 908 (41.7%; 95% confidence interval [CI], 39.6%-43.8%) had VISP, but the occurrence of VISP varied substantially across different HIV vaccine product types: 399 of 460 (86.7%; 95% CI, 83.3%-89.7%) adenovirus 5 product recipients, 295 of 552 (53.4%; 95% CI, 49.2%-57.7%) recipients of poxvirus alone or as a boost, and 35 of 555 (6.3%; 95% CI, 4.4%-8.7%) of DNA-alone product recipients developed VISP. Overall, the highest proportion of VISP (891/2176 tested [40.9%]) occurred with the HIV 1/2 (rDNA) EIA kit compared with the rLAV EIA (150/700 tested [21.4%]), HIV-1 Plus O Microelisa System (193/1309 tested [14.7%]), and HIV 1/2 Peptide and HIV 1/2 Plus O (189/2150 tested [8.8%]) kits. Only 17 of the 908 participants (1.9%) with VISP tested nonreactive using the HIV 1/2 (rDNA) kit. All recipients of a glycoprotein 140 vaccine (n = 70) had VISP, with 94.3% testing reactive with all 3 EIA kits tested. Among 901 participants with VISP and a Western blot result, 92 (10.2%) had a positive Western blot result (displaying an atypical pattern consistent with vaccine product), and 592 (65.7%) had an indeterminate result. Only 8 participants with VISP received a vaccine not containing an envelope insert.

Conclusions: The induction of VISP in HIV vaccine recipients is common, especially with vaccines containing both the HIV-1 envelope and group-specific core antigen gene proteins. Development and detection of VISP appear to be associated with the immunogenicity of the vaccine and the EIA assay used.

Figure 1

Algorithm for HIV infection and VISP testing Specimens from a participant’s last available study visit were tested for VISP using an algorithm that started with 3 different EIA tests. The algorithm proceeded directly to the Western blot if all three EIA tests were reactive. If 1 or 2 of the EIA tests were initially reactive then the EIAs were repeated in duplicate per manufacturer’s instructions to confirm reactivity before proceeding to the Western blot. Western blots were interpreted according to CDC criteria. Additionally, evaluation of the Western blot required consideration of whether the bands were consistent with a vaccine-induced response or an actual HIV infection. Specimens that were Western blot positive or indeterminate had quantitative RNA PCR testing. Additional HIV nucleic acid tests were performed to aid in a clear interpretation of infection status. If HIV infection was suspected, specimens from participant were re-drawn and the algorithm repeated until a clear interpretation was made.

Figure 2

Flow of Subjects