Vaccine-Induced Seroreactivity Impacts the Accuracy of HIV Testing Algorithms in Sub-Saharan Africa: An Exploratory Study

Abstract

The detection of vaccine-induced HIV antibody responses by rapid diagnostic tests (RDTs) may confound the interpretation of HIV testing results. We assessed the impact of vaccine-induced seroreactivity (VISR) on the diagnosis of HIV in sub-Saharan Africa. Samples collected from healthy participants of HIVIS and TaMoVac HIV vaccine trials after the final vaccination were analyzed for VISR using HIV testing algorithms used in Mozambique and Tanzania that employ two sequential RDTs. The samples were also tested for VISR using Enzygnost HIV Integral 4 ELISA and HIV western blot assays. Antibody titers to subtype C gp140 were determined using an in-house enzyme-linked immunosorbent assay (ELISA). The frequency of VISR was 93.4% (128/137) by Enzygnost HIV Integral 4 ELISA, and 66.4% (91/137) by western blot assay (WHO interpretation). The proportion of vaccine recipients that would have been misdiagnosed as HIV-positive in Mozambique was half of that in Tanzania: 26.3% (36/137) and 54.0% (74/137), respectively, p < 0.0001. In conclusion, the HIV RDTs and algorithms assessed here will potentially misclassify a large proportion of the HIV vaccine recipients if no other test is used. Increased efforts are needed to develop differential serological or molecular tools for use at the point of care.

Keywords: HIV diagnostic algorithms; HIV misdiagnosis; vaccine-induced HIV antibodies; vaccine-induced seroreactivity.

Figure 1

Frequency of VISR. Samples collected four weeks after the final vaccination were evaluated for VISR using rapid point-of-care tests and ELISA (A). The highest rates of VISR were seen when using Enzygnost HIV Integral 4 ELISA and SD Bioline HIV-1/2 3.0. HIV misdiagnosis according to western blot interpretation criteria (B). The VISR results were interpreted using the criteria detailed in Table 1 (CDC, CRSS, WHO, and ARC criteria). The majority of the vaccinees would have been misclassified as HIV-infected using the CDC and CRSS interpretation criteria.

Figure 2

Proportion of vaccinees misdiagnosed as HIV-infected. Samples were tested for VISR using HIV testing algorithms used in Mozambique and Tanzania that use two sequential rapid diagnostic tests: Alere Determine^TM HIV-1/2 and Uni-Gold^TM HIV-1/2 in Mozambique, SD Bioline HIV1/2 3.0 and Uni-Gold^TM HIV-1/2 in Tanzania. Patients were considered HIV-negative if the screening assay was negative and HIV-infected if both assays were reactive. Fisher’s exact test was used to compare the frequency of VISR between the two HIV testing algorithms. The proportion of vaccine recipients who would have been misclassified using the Mozambican HIV testing algorithm was half of that misclassified by the Tanzanian algorithm.

Figure 3

Magnitude of antibody responses among vaccinees. Mann-Whitney U test was used to compare the level of antibody responses between vaccine recipients incorrectly identified as HIV-positive and those who were HIV-negative. In both HIV testing algorithms (A,B), significantly higher antibody titers were found in vaccinees who were misclassified as HIV-positive than in those classified as HIV-negative. The red and blue circles represent reactive and non-reactive vaccine recipients, respectively.