Paper # 623 
A Randomized Controlled Trial Comparing the Efficacy and Safety of 4 Intramuscular Double Doses or 4 Intradermal Low Doses with 3 Intramuscular Standard Doses of HBV in HIV-infected Adults: Results of the ANRS HB03 VIHVAC-B Trial
Odile Launay*1, D van der Vliet1, A Rosenberg1, M-L Michel2, O Lortholary3, N Colin de Verdičre4, L Slama5, L Piroth6, D Rey7, F Carrat8, and ANRS HB03 Trial Group
1Univ Paris Descartes, Hosp Cochin, France; 2Inst Pasteur, Paris, France; 3Univ Paris Descartes, Hosp Necker, France; 4Hosp Saint Louis, Paris, France; 5Hosp Tenon, Paris, France; 6Hosp Haut Bocage, Dijon, France; 7Hosp Univ, Strasbourg, France; and 8Univ Pierre and Marie Curie, Hosp Saint Antoine, Paris, France
Background: HIV+ persons are hypo-responsive to hepatitis B virus
(HBV) vaccination. Because HBV infection is more frequent but also more severe
in HIV+ patients, alternative schedules conferring a higher immune
response than standard regimen are needed.
Methods: In
a prospective, multicenter, randomized controlled trial, stratified
according to CD4 cell count (200 to 349, >350
cells/µL) and viral load (HIV-RNA <50, >50 copies/mL), 437 HBV-seronegative HIV+ adults were
randomized to receive 3 intramuscular (IM) standard doses (20 μg) of recombinant hepatitis B vaccine at weeks 0, 4, and 24 (group
1, n = 145), 4 IM double doses (40 μg) (group 2, n = 148) or 4 intradermal (ID) low doses (4 μg) (group 3, n = 144), the latter 2 at weeks 0, 4, 8, and
24. Sera were collected after each vaccine dose and centralized for
quantification of hepatitis B surface antibody (anti-HB) titres with a
standardized assay. Subjects with anti-HBs >10 mIU/mL and >
100 mIU/mL at week 28 (4 weeks after the last injection) were defined as responders
(main endpoint) and high responders, respectively.
Results: The
median age was 42.8 years (interquartile range (IQR), 36
to 49); 67% were male; 83% were on HAART; 78% had HIV-RNA <50 copies/mL and the median CD4-cell count was 503 cells/µL (IQR, 394 to 645). In an intent-to-treat analysis (missing = failure), the
percentage of responders and high responders were 65% and 40%
respectively in group 1, 82% and 72% in group 2, and 77% and 53% in group 3 (P =0.002
and P <0.0001, respectively). At week 28, the geometric mean
anti-HB titres were 57 (95% Confidence Interval (95%CI) 32 to 105), 1352 (95%CI
821 to 2209) and 111 (95%CI 69 to 178) mIU/mL in group 1, 2 and 3 respectively
(P<0.0001). At week 8, after the 2 first doses of vaccine, responder’s
rates were 22%, 46% and 27% in group 1, 2 and 3, respectively (P<0.0001).
There were no serious adverse events associated with the vaccine. Local inflammatory reactions were more frequent after ID
immunization. Vaccination arm (IM standard doses
regimen), male gender, increased age, active smoking and HIV-RNA > 50 copies/mL were all
independently associated with lower response to vaccination.
Conclusions: Both the 4 IM double doses and the 4 ID low doses regimen improved
serological response comparing with standard regimen of HBV vaccine. The well
tolerated 4 IM double doses schedule achieving more rapid protection and higher
anti-HB titres should become the standard of care in this setting.
|
