Safety and immunogenicity of a tetravalent dengue vaccine (CYD-TDV) in HIV-positive adults aged 18-50 years in Brazil: Results from a phase II, randomized, observer-blind, placebo-controlled trial.

Dengue is a common arboviral infection that poses a serious health concern worldwide, including Latin America. Our study assessed the safety and immunogenicity of CYD-TDV, a recombinant, live-attenuated, tetravalent dengue vaccine, among HIV-infected adults in Brazil, with previous exposure to dengue infection, and maintained on antiretroviral therapy. This observer-blind, placebo controlled, phase II study (NCT02741128) enrolled participants aged 18-50 years, randomized 2:1 to receive CYD-TDV or placebo subcutaneously at 0, 6, and 12 months. Serological assessments were performed using plaque reduction neutralization assays at baseline and 28 days following each vaccination. Overall, 133 participants were randomized (CYD-TDV, n = 89; placebo, n = 44). At day 28, post-initial vaccination, participants receiving CYD-TDV reported 3.11- to 6.37-fold increase in neutralizing antibody geometric mean titers compared with those at baseline across dengue virus serotypes 1-4 but were sustained after 3 doses. No notable immune responses were observed to any of the serotypes in the placebo group. The safety profiles were comparable across both study groups. In the CYD-TDV and placebo groups, pain was the most commonly reported injection site reaction post-first injection in 18.4% and 29.5% participants, respectively. There were no reports of Grade 3 solicited injection site reactions post-CYD-TDV administration. No safety signals were detected after CYD-TDV administration, including immediate unsolicited AEs/ARs, SAEs/AESIs, or HIV-related conditions. None of the participants discontinued the study due to an AE, and no deaths were reported. CYD-TDV demonstrated adequate safety and robust immunogenicity against all dengue serotypes in HIV-positive adults receiving prior antiretroviral treatment.