Immunogenicity and reactogenicity of yellow fever vaccine in people with HIV

Abstract

Objective: To evaluate immunogenicity and reactogenicity of Yellow Fever (YF) vaccine in people living with HIV (PLWH) compared to HIV-uninfected controls. Design: In this longitudinal interventional trial (NCT03132311), PLWH with CD4 ≥200 cells/μL and controls, aged 18–59, without a previous history of YF vaccination received a single standard dose of YF vaccine (17DD) and were followed at Days 5, 30 and Year 1. Methods: YF-neutralization titers were measured at Days 0, 30 and Year 1 and geometric mean titers (GMT) were calculated. Adverse events (AE) and YF virus detection were measured at Days 5 and 30. Linear regression evaluated factors associated with YF-neutralization titers. Results: 218 PLWH and 82 controls were included. At baseline, all PLWH were using antiretroviral therapy; 92.6% had undetectable HIV viral load (VL) and median CD4 was 630 cells/μL (IQR 463–888). YF vaccine was safe and there were no serious AEs. At Day 30, seroconversion was observed in 98.6% of PLWH (95%CI: 95.6–99.6) and in 100% of controls (95%CI: 93.9–100); at Year 1, 94.0% of PLWH (95% CI: 89.6–96.7) and 98.4% of controls (95%CI 90.3–99.9) were seropositive. PLWH had lower GMTs than controls at Day 30 and Year 1. Baseline VL >1,000 copies/mL, low CD4 counts and low CD4/CD8 ratio were associated with lower YF-neutralization titers. Conclusions: YF vaccine is safe in PLWH with CD4 ≥ 200 cells/μL. YF vaccine immunogenicity is impaired in PLWH, particularly among those with high VL, low CD4 counts and low CD4/CD8 ratio at vaccination and YF-neutralization titers decays over time.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics

“…We showed recently that the 17DD vaccine was safe and well tolerated in PLWH. 20 However, we found that 17DD viremia was associated with adverse events in PLWH and HIV-uninfected controls (HIV(-) controls). 20 In this study, we aimed to further explore factors associated with the occurrence of 17DD viremia in PLWH and HIV(-) controls.…”

“… 20 However, we found that 17DD viremia was associated with adverse events in PLWH and HIV-uninfected controls (HIV(-) controls). 20 In this study, we aimed to further explore factors associated with the occurrence of 17DD viremia in PLWH and HIV(-) controls. In addition, we describe the kinetics of hematological and liver laboratorial parameters and assess whether 17DD viremia and HIV status were associated with the occurrence of laboratorial abnormalities.…”

“…This study is a secondary analysis of a prospective cohort study that enrolled PLWH and HIV(-) controls to receive a standard dose of 17DD vaccine at Instituto Nacional de Infectologia Evandro Chagas (INI/Fiocruz) from 2017 to 2018. 20 Participants aged 18 and 59 years with no history of YF previous illness or vaccination were eligible for the study. Additional eligibility criteria were not presenting known contraindications to the vaccine, such as immune disorders (i.e., PLWH with CD4 < 200 cells/µL, primary immunodeficiency, malignancy, immunosuppressive or immune response modifying drugs using, thymic dysfunction, having received blood products or immunoglobulins in the last three months), pregnancy or breastfeeding, having received a live attenuated virus vaccine in the last month, current symptoms of severe acute illness or fever ≥ 38 °C.…”

Impact of HIV-Related Immune Impairment of Yellow Fever Vaccine Immunogenicity in People Living with HIV—ANRS 12403

“…For PLWH, safety and immunogenicity reports are mostly limited to small observational studies and case reports [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ], except for a few cohort studies [ 16 , 17 , 18 , 19 , 20 , 21 ], and indicate that markers of HIV disease progression are associated with a lower level and shorter persistence of YF neutralization antibody (NAb) titers [ 11 , 17 , 18 , 20 ]. To address this, a longitudinal prospective non-randomized interventional trial with 280 PLWH was conducted and confirmed the safety of the YF vaccine in PLWH with CD4 + cell count ≥200 cells/mm 3 [ 22 ]. However, immunogenicity was impaired in PLWH, particularly in those with a high viral load, low CD4 + T cell count, and low CD4/CD8 ratio at vaccination.…”

“…To further investigate the mechanisms that could impair YF vaccine immunogenicity in PLWH, our study evaluated the pre-vaccination frequencies of several cellular subsets and inflammation markers that are affected by HIV infection in a longitudinal interventional trial that evaluated the immunogenicity and reactogenicity of the YF vaccine in PLWH and HIV-negative controls [ 22 ].…”