Vaccine-Induced HIV Seropositivity/Reactivity in Noninfected HIV Vaccine Recipients

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. JAMA. 2010;304(3):275-283 www.jama.com