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Randomized Trial Comparing a 3-Dose Regimen to a Standard 2- Dose Regimen of Hepatitis A Vaccine in HIV-infected Adult Patients with CD4+ T Cells between 200 and 500 per mm3 (HEPAVAC Study)
Odile Launay*1, S Grabar1, E Gordien2, C Desaint1, J Dimet1, D Jegou1, P M Girard3, D Salmon1, S Abad2, D Rey4, and HEPAVAC Study Group
1Hosp Cochin, Paris, France; 2Hosp Avicenne, Bobigny, France; 3Hosp St Antoine, Paris, France; and 4Univ Hosp Strasbourg, France
Background: HIV-infected patients have weak responses to
vaccine and may require revised immunization regimens. The immunogenicity
and safety of 3-dose vs 2-dose hepatitis A vaccine (HAV)
were compared in HIV-infected patients.
Methods: In a prospective open trial, 93 HAV-seronegative HIV-infected patients, 21 to 55 years of age, whose
CD4 T cells ranged between 200 and 500 per mm3 and plasma viral load
≤50,000 copies/mL were randomized to receive
either 3 hepatitis A vaccine doses (1440 ELISA units) at weeks 0, 4, and 24, or
2 vaccine doses 24 weeks apart. Anti-HAV antibody titres were measured 4 weeks
after each vaccination using a quantitative immunoenzymatic
test (Diasorin). Primary endpoint was the percentage
of patients with seroconversion (antibodies titers ≥20 mUI/mL) 4 weeks
after the last vaccine dose (week 28). Univariate and
multivariate analyses were performed to determine predictive factors of
response to vaccine administration.
Results: In an intent-to-treat analysis, the
percentage of seroconversion at
week 28 was 71% in the 3 vaccine doses, and 58% in the 2 vaccine doses (p = 0.2). At week 28, the geometric mean
HAV antibody titre was 290 mUI/mL
in the 3-dose group, and 125 mUI/mL in the 2-dose
group (p = 0.08). A statistically
significant higher seroconversion rate was associated
with 3 doses than with standard 2 doses for patients with CD4+ T-cell counts <350
cells/mm3 (73% vs 39%, p = 0.02). After
the first dose of vaccine, seroconversion was
observed in only 42% of patients. There were no serious adverse events
associated with the vaccine. Multivariate analysis showed no vaccine dose
effect, but indicated that smoking was an independent predictor of non-response
to vaccine (0R = 2.78, 95%CI 1.03 to 7.69, p
= 0.02).
Conclusions: In HIV-infected adults with CD4+ T
cells between 200 and 500 per mm3, immunogenicity
of HAV vaccine is low, with only 58% of seroconversion
in the 2-dose immunization regimen. This is much lower than reported rates of
100% in healthy adults. A third vaccine dose was safe and increased the
antibody titres and the rate of seroconversion in
patients with CD4+ T cell <350/mm3. These results
suggest that anti-HAV antibody titres should be measured after immunization
even in those with CD4 cells >350/mm3 and that an increase in
immunizations may be warranted in this population.
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