Safety and immunogenicity of yellow fever vaccine in HIV+ patients: ANRS EP46 NOVAA
Background: Yellow fever
vaccine (YFV) uses a live attenuated viral strain and is contra-indicated in
HIV-infected patients with < 200 CD4 cells/mm3. Whether YFV is safe
and efficacious in patients with higher CD4 count remains to be clarified. We
performed a prospective, comparative, non randomized study to assess safety and
immunogenicity of YFV in uninfected (HIV−) and HIV-infected (HIV+) adults with CD4 count >350/mm3.
Methods: 40 YFV-naïve HIV+ adults
under antiretroviral therapy (ART) with CD4 >350/mm3 and plasma HIV RNA < 50
cp/ml for at least 6 months, and 31 HIV− healthy adults received primary vaccination
with YFV 17D strain. Follow-up was performed at day 7, 14, 28, 91, 365. Safety
was assessed by grading clinical and biological adverse events (AEs), detection
of YFV viremia using RT‑PCR, CD4 count and plasma HIV RNA levels. Serologic
response was assessed by neutralizing antibody titers using a reference plaque
reduction neutralizing test (PRNT) and a new pseudotype based neutralization
assay, with protection associated titers >10 and >95% neutralizing
activity, respectively.
Results: At baseline, HIV+ subjects
were mostly male (95%), median age: 44 years, median CD4: 702/mm3 (IQR 553,
840), 23% were CDC stage C. HIV− patients were mostly female (88%), median age:
35 years, median CD4: 902/mm3 (IQR 635, 1247). Adverse events were reported by
42% of HIV− and 30% of HIV+, mostly headaches, asthenia, myalgia and local
reactions of grades 1 or 2. None of the 3 SAE reported, with 1 death, was
related to vaccination.76% of HIV− and 82% of HIV+ subjects had positive YFV
viremia at D7 only. There was a significant decrease in CD4 count in both groups
at D7 which was more pronounced in HIV− than in HIV+ patients (261.5 vs 111.5
cells decrease from baseline, respectively, p=0.0003). There was no HIV
breakthrough during follow-up. All patients (100%) in both arms developed
protective neutralizing antibody levels with both assays since day 28 and for a
year after injection.
Conclusions: In HIV+ patients with CD4
>350/mm3 and suppressed viral replication on ART, YFV was as safe and
immunogenic as in HIV− subjects. Long-term follow-up will tell whether protection
is maintained over time.
N. Colin de Verdière1, V. Meiffrédy2, C. Durier2, O. Launay3, S. Matheron4, S. Mercier-Delarue5, A. Boulay5, J.-M. Molina1, F. Simon5, ANRS EP46 NOVAA Group
1Saint-Louis Hospital , APHP, Infectious Diseases, Paris, France, 2SC10-US019, INSERM, Villejuif, France, 3Cochin Hospital, APHP, CIC de Vaccinologie Cochin Pasteur, Paris, France, 4Bicêtre Hospital, AP-HP, Infectious Diseases, Paris, France, 5Saint-Louis Hospital, APHP, Microbiology, Paris, France