Safety and immunogenicity of measles vaccine, varicella vaccine and hepatitis-a vaccine in HIV exposed and HIV-unexposed South African children
Date
2020
Authors
Mutsaerts, Eleonora Alexandra Marie Louise
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Abstract
Introduction: Children living with HIV and HIV-exposed uninfected (HEU) children
have increased risk of infectious diseases that may be compounded by modified
immune response to vaccination or faster waning of immunity. We evaluated
persistence of measles antibodies in HEU children and children living with HIV. In
addition, we assessed the immunogenicity and safety of early measles, varicella and
hepatitis-A vaccination in HIV-unexposed and HEU children.
Methods: Durability of measles response at 4.5 years of age was measured
following measles vaccination at 9 and 15-18 months of age in HIV-unexposed
(n=95), HEU (n=84) and HIV-infected children previously randomized to start
antiretroviral therapy (ART) when clinically/immunologically indicated (HIV/Def-ART;
n=62) or to immediate ART, that was interrupted at 12 months (HIV/Immed-ART-12;
n=70) or 24 months (HIV/Immed-ART-24; n=70) of age.
In a prospective cohort, HEU (n=71) and HIV-unexposed (n=212) children received
measles vaccination at 6 and 12 months of age, and one dose of either varicella or
hepatitis-A vaccine at 18 months of age. Vaccine-specific antibody concentrations
were measured before and one month after each vaccine dose.
Results: At 4.5 year of age, in comparison with HIV-unexposed children,
HIV/Immed-ART-12 and HIV/Immed-ART-24 groups had significantly lower
proportions with measles seropositive antibody titers (≥330 mIU/mL), while these
were similar in HEU and HIV/Def-ART children, who initiated ART at median 5.8
months of age.
In the prospective cohort study, after one dose of measles vaccine at 6 months of
age, 42% of HIV-unexposed and 46% of HEU children had seropositive titers (≥330
viii
mIU/mL) at 7 months of age, which increased to 99% in HIV-unexposed and 95% in
HEU one month after receipt of the second dose at 12 months of age.
A single dose of hepatitis-A vaccine induced seropositive titers in 92% of HIV
unexposed and 83% of HEU children (p=0.144). Seroconversion (>50 mIU/mL)
following a single dose of varicella vaccine was modest (44%) and the same in HIV
unexposed and HEU children.
No difference in immune response was observed between HIV-unexposed and HEU
children following measles, varicella and hepatitis-A vaccination.
Conclusions: Children living with HIV who interrupted ART experienced faster
waning of measles humoral immunity compared to HIV-unexposed children,
emphasizing the need for continuous ART treatment. A two-dose measles vaccine
schedule, with the first dose administered at 6 months of age, induced antibody
responses in the majority of HIV-unexposed and HEU children.
Hepatitis-A vaccination resulted in most children achieving seropositive antibody
levels. The modest seroconversion rates after varicella vaccination, which were
lower than expected in both groups, warrant further investigation.
Description
A thesis submitted in fulfilment of the requirements for the degree of
Doctor of Philosophy to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2020