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

Abstract

Context Induction of protective anti-HIV immune responses is the goal of an HIV vaccine. However, this may cause a reactive result by routine HIV testing in the absence of HIV infection. Objective This study evaluated the frequency of vaccine-induced seropositivity/reactivity (VISP) in HIV vaccine trial participants. Design, Setting, and Participants A routine diagnostic HIV algorithm was used for participants who completed 25 phase 1 and two phase 2 vaccine trials from 2000–2010 conducted in the United States, South America, Thailand, and Africa. Main Outcome Measures Three common FDA-approved enzyme immunoassay (EIA) HIV antibody kits were used to determine VISP. VISP was defined as being reactive on ≥ 1 EIA test, HIV-1 negative by nucleic acid testing, and Western blot negative, indeterminate, or atypical positive (profile consistent with vaccine product). Results Among 2176 HIV uninfected participants 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 (40.9%; 891 of 2176 tested) occurred with the HIV 1/2 (rDNA) EIA compared to the rLAV EIA (21.4%; 150 of 700 tested), HIV-1 Plus O Microelisa System (14.7%; 193 of 1309 tested), and HIV 1/2 Peptide and HIV 1/2 Plus O (8.8%; 189 of 2150 tested) kits. Only 17 (1.9%) of the 908 participants with VISP tested nonreactive using the HIV 1/2 (rDNA) kit. All recipients of a gp140 vaccine (n= 70) had VISP, with 94.3% tested reactive to all three EIA kits tested. Among 901 participants with VISP and a Western blot result, 92 (10.2%) had a positive Western blot (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 env insert. Conclusions The induction of VISP in HIV vaccine recipients is common especially with vaccines containing both the HIV-1 envelope and gag proteins. Development and detection of VISP appear to be associated with the immunogenicity of the vaccine and the EIA assay used.

Malaria Diagnostics in Clinical Trials

“…18 In persons with vaccineinduced seropositivity, serial testing or multi-test algorithms are required to maintain the specificity of true infection endpoints for the trial data and for the participants. 19 Thus, the first step toward obtaining accurate malaria diagnostics is to ensure that the appropriate assay is selected. The appropriate assay will depend on trial-specific research/ clinical question(s) and the epidemiologic environment at the study site(s).…”

Vaccine-induced HIV seropositivity: A problem on the rise

“…1 Vaccine-induced seropositivity (VISP) is a common outcome of HIV vaccine trials, 2 mostly associated with vaccines containing envelope inserts. [2][3][4][5][6] Current HIV screening policy relies on highly sensitive enzyme immunoassays detecting antibodies against different proteins, most often p24, HIV-1 gp41 and HIV-2 gp36. Although 4th generation tests reduce the size of the diagnostic window by combining HIV antibody and p24 antigen detection, 7-10 many clinical laboratories still use 3rd generation assays.…”

Performance of a Redesigned HIV Selectest Enzyme-Linked Immunosorbent Assay Optimized To Minimize Vaccine-Induced Seropositivity in HIV Vaccine Trial Participants

“…Overall, 41.7% of HIV vaccine recipients in 27 HIV Vaccine Trials Network (HVTN)-sponsored HIV vaccine trials of 25 different vaccine products, conducted between 2000 and 2010, were found to exhibit VISP at the trial exit date when VISP was surveyed across multiple serological kits (9). VISP frequencies ranging from 6% to as high as 80% to 100% have been associated with vaccination protocols employing adenovirus (9,10) and modified vaccinia virus Ankara (MVA) (32), depending on which serological kits were used. In contrast, low levels of VISP were observed in RV144 vaccine recipients tested with the Vironostika HIV-1 kit, although the same kit yielded divergent results in other trials (8,9) (HVTN, unpublished data).…”

“…VISP frequencies ranging from 6% to as high as 80% to 100% have been associated with vaccination protocols employing adenovirus (9,10) and modified vaccinia virus Ankara (MVA) (32), depending on which serological kits were used. In contrast, low levels of VISP were observed in RV144 vaccine recipients tested with the Vironostika HIV-1 kit, although the same kit yielded divergent results in other trials (8,9) (HVTN, unpublished data). VISP peaked 6 months following the final vaccination, at which time seroreactivity was detected by the Vironostika kit in 28 (0.4%) of 7,015 tested vaccine recipients, compared to 4 (0.06%) of 7,099 tested placebo recipients (33).…”

“…VISP peaked 6 months following the final vaccination, at which time seroreactivity was detected by the Vironostika kit in 28 (0.4%) of 7,015 tested vaccine recipients, compared to 4 (0.06%) of 7,099 tested placebo recipients (33). VISP frequency is also highly dependent on the specific assay system used, with frequencies ranging from 6% to 92% for the same group of serum samples tested with different kits in one extreme example (9). VISP can be a long-term problem; it has been shown to re-main for up to 15 years after vaccination, during which time the link to an individual's vaccination history may be lost (3,9,34).…”