Viral load is the only factor associated
with a poorer antibody response to the yellow fever vaccine in patients with
HIV, according to a French study published in the online edition of the Journal of Acquired Immune Deficiency
For patients vaccinated after diagnosis
with HIV, an undetectable viral load was the “unique determinant” of the
preservation of protective levels of antibodies.
“This study of a large series provides new
data about the immunogenicity of yellow fever immunisation in HIV patients,”
comment the authors.
The re-emergence of yellow fever in endemic
countries in sub-Saharan Africa and South America is causing great concern. The
fatality rate is as high as 50% for symptomatic patients.
However, a live attenuated vaccine that
provides high levels of protection against this infection is available. Some
99% of patients have antibodies against the infection within 30 days of immunisation,
and protection may persist for 30 years (however, the World Health Organization [WHO] recommends a booster dose
of the vaccine after ten years).
Yellow fever vaccine and booster doses are
recommended for HIV-positive patients with a CD4 cell count above 200 cells/mm3
who live in – or, in some cases, are visiting – endemic countries. As a live
vaccine, there are some concerns about the safety of immunisation for patients
with lower CD4 cell counts.
However, there is limited information on
the efficacy and safety of the vaccine in patients with HIV.
Therefore, investigators in Paris designed
a study with a primary objective of assessing the proportion of HIV-positive
patients vaccinated against yellow fever (primary and booster doses)
who did not develop a sufficient antibody response to protect them against this
The study was conducted between 2007 and
2008 and involved 364 patients.
An insufficient response to the
immunisation was defined as an antibody titre below 1:10.
Overall, 93% of patients had an antibody
titre above 1:10. This included 92% of patients who had received the vaccine
ten years before the sampling in this study.
“Yellow fever immunisation is effective in
HIV patients,” comment the authors. “The proportion of patients with an
antibody titre >1:10 [98%] was especially high within one year following
A total of nine of the 240 patients who
were vaccinated after their diagnosis with HIV had an antibody titre below the
protective level. Viral load in these patients was significantly higher
compared to individuals who had protective antibody tires (p < 0.03). Each
log10 increase in viral load doubled the risk of having a tire below
the crucial 1:10 threshold (OR = 2.1; 95% CI, 1.2-3.78).
Analysis of the 79 patients who received
their initial dose of the vaccine after their diagnosis with HIV found an even
stronger association between viral load and the lack of a protective antibody
titre (OR = 3. 73 per 1010; 95% CI, 1.14-12.28).
“Suppressed plasma viral load at baseline
was the unique determinant for the persistent of levels of antibodies above
1:10,” note the authors.
Shorter duration of HIV suppression below
400 copies/ml was also associated with an antibody titre below 1:10 (OR = 1.05
per year; 95% CI, 1.005-1.09).
At the time of immunisation, 14 patients
had a CD4 cell count below 200 cells/mm3. Furthermore, six of these
individuals also had a viral load above 400 copies/ml. The interval between
administration of the vaccine and measurement of antibody response was a median
of 4.6 years. All the patients had an antibody tire above 1:10.
The investigators believe their results
have implications for the care of HIV-positive patients.
They suggest that “in cases where there is
travel to a yellow fever-endemic country, we suggest that neutralizing antibody
determination be performed prior to departure, whatever the time since a
previous immunisation, especially in patients with non-controlled HIV RNA at
the time of travel or immunisation.”
The authors conclude, “patients with
non-protective neutralising antibodies might be revaccinated earlier than recommended
by current guidelines, whereas revaccination might be avoided in patients with