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.

The Future of HIV Vaccine Development, Learned Lessons from COVID-19 Pandemic

“…To improve the accuracy of HIV diagnostic algorithms, two to three RDTs are used in series or in parallel as screening, confirmatory, or tiebreaker tests. Considering the emotional trauma and social harms caused by HIV misdiagnosis, it is imperative that the RDT-based diagnostic strategies are able to discriminate HIV antibodies elicited by vaccination from those generated in response to an infection [34].…”

Proceedings of the Online Conference “Vaccines and Vaccination during and Post COVID Pandemics” (7–9 December 2022)

“…The results revealed that the Tanzanian diagnostic algorithm would have misdiagnosed as HIV-1 infected 54%, and the Mozambican—26% of the vaccinated healthy volunteers. However, the number of misdiagnoses decreased over time, and three years after vaccination, none of the 20 serum samples collected at that time tested HIV-1 positive using rapid diagnostic tests [ 59 ]. The reported results suggested that the HIV diagnostic algorithms used in these countries would have misclassified the healthy vaccine recipients as HIV-positive.…”