immune response to most vaccines is impaired in people with HIV, according to
the results of a meta-anlaysis published in the online edition of Clinical Infectious Diseases. Comparison
with vaccination outcomes in HIV-negative individuals showed that the effect of
immunisations waned more rapidly in people with HIV.
showed a rapid decrease in seroprotection after immunization in HIV-infected
patients,” comment the authors.
The study has
important implications, showing that vaccine responses needed to be closely
monitored in people living with HIV and revaccination provided when antibody
levels are no longer protective.
It’s already known
that initial immune responses to most vaccines are impaired in people with HIV. However, little is known about the persistence of vaccine-induced
antibodies in the long-term. This is an important gap in knowledge. Recommendations
about booster injections for people with HIV are currently based on data
obtained from HIV-negative individuals.
A team of French
investigators therefore performed a meta-analysis and systematic review of data
from prospective studies reporting on the long-term persistence of antibody
concentrations after vaccination with licensed products.
A total of 59
studies were reviewed and 19 were included in the meta-analysis.
Results of the
meta-analysis showed that less of half of people with HIV who had a primary
response to hepatitis B vaccination still had protective immunity two years after
immunisation (28% in adults; 61% in children), and that only 17% were still
protected after five years. Doubling the vaccine dose did not improve long-term
A slight decrease
over time in the protective immunity provided by hepatitis A vaccination was
also observed. Pooled results showed that 92% of individuals were still
protected two years after vaccination, and 82% after five years.
the measles vaccine was restricted to studies focusing on children who had acquired HIV vertically (through mother-to-baby transmission), immunised between the ages of 6 and 42 months with the MMR vaccine.
Pooled results showed that 68% of initial responders still have protective
antibodies after two years, falling to 40% after five years.
of antibodies to tetanus were present in 74 and 43% of initial responders two
and five years after immunisation, respectively. Few studies reported on the
long-term responses to vaccination against polio, pertussis and diphtheria. However,
all showed that the duration of protection was shorter for children with HIV compared to HIV-negative children.
long-term responses to immunisation against Streptococcus
pneumoniae included studies examining either the PCV or PPSV23 vaccines.
After PPSV23 in adults, rates of decrease in antibody concentrations were
either similar or more rapid than those observed in HIV-negative adults. After
five years, antibody levels were no longer protective. This was more likely to be the case for people with a low CD4 cell count or detectable viral load at the
time of vaccination. Children with HIV who initially responded to Streptococcus pneumoniae immunisation
had a significantly greater decline in antibody levels during follow-up
compared to HIV-negative children.
Rates of long-term
sero-protection among vertically infected children with an initial response to Haemophilus inluenzae b varied between
16% and 78%.
One study looked
at responses to the varicella vaccine, showing that less than 50% of children
still had detectable antibodies one year after immunisation. Response to yellow
fever vaccine was only examined in retrospective studies, their results showing
that antibody levels fell more rapidly in people with HIV compared to HIV-negative
individuals, with only 17 to 23% still having protective antibody levels ten
years post-vaccination. A single study examined the long-term response to
vaccination against Japanese encephalitis among children taking HIV therapy.
Only a handful of initial responders had lost protective immunity after three
years, suggesting the long-term effectiveness of the vaccination in this
seroprotection…is shorter in HIV-infected patients than in otherwise healthy
persons for most licensed vaccines,” comment the authors.
They believe their
results have several implications:
- Hepatitis B: Antibodies should be
measured yearly in adults and every two to five years in children. Closer
monitoring could be considered for people whose initial response to the vaccine
- Hepatitis A: Individuals with an
increased risk of this infection (men who have sex with men, individuals with
chronic liver disease, travellers) should have antibody responses checked every
- Tetanus: A booster every ten years should
- Measles: The initial should ideally be
administered after children have started HIV therapy. If viral load is
undetectable, two doses are recommended. Children who are vaccinated before
they start antiretrovirals, or who have a detectable viral load, should receive
a third dose two to five years after initial vaccination.
- Yellow fever: Immunity wanes more
rapidly in people with HIV. Antibody levels should be assessed in people at risk of this infection and revaccination is recommended for people who lack protective immunity.
- Streptococcus pneumoniae: Data are too preliminary to inform optimal timing of booster
injections for adults.
were concerned that the median number of participants per study was only 40. They
comment: “Data on immunogenicity of vaccines in the immunocompromised host are
scarce and the small samples in each category give little power for comparisons
between age classes or vaccine schemes.”
suggest that the clinical implications of their findings should be explored in
larger prospective studies. They also believe their results have implications
for future vaccine research: “The evaluation of new vaccines that specifically
target persons with impaired immunity…should confront clinical effectiveness
with precise evaluation of both humoral and cellular responses, in an attempt
to establish reliable correlates of protection in these populations.”