Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial

[Guest guest]

JAMA. 2011 Apr 13;305(14):1432-40.

Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low

doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized

controlled trial.

Launay O, van der Vliet D, Rosenberg AR, Michel ML, Piroth L, Rey D, Colin de

Verdi¨¨re N, Slama L, K, Lortholary O, Carrat F; ANRS HB03 VIHVAC-B

Trial.

Collaborators (71)

Paris Descartes University, France. odile.launay@...

Abstract

CONTEXT: Alternative schedules more immunogenic than the standard hepatitis B

vaccine regimen are needed in patients with human immunodeficiency virus 1

(HIV-1) infection.

OBJECTIVE: To compare the safety and immunogenicity of 4 intramuscular

double-dose and 4 intradermal low-dose regimens vs the standard hepatitis B

vaccine regimen.

DESIGN, SETTING, AND PARTICIPANTS: An open-label, multicenter, 1:1:1

parallel-group, randomized trial conducted between June 28, 2007, and October

23, 2008 (date of last patient visit, July 3, 2009) at 33 centers in France with

patients enrolled in French National Agency for Research on AIDS and Viral

Hepatitis trials in adults with HIV-1 infection who were hepatitis B virus (HBV)

seronegative and having CD4 cell counts of more than 200 cells/¦ÌL.

INTERVENTION: Patients were randomly assigned to receive 3 intramuscular

injections of the standard dose (20 ¦Ìg) of recombinant HBV vaccine at weeks 0,

4, and 24 (IM20 ¡Á 3 group, n = 145); 4 intramuscular double doses (40 ¦Ìg [2

injections of 20 ¦Ìg]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (IM40

¡Á 4 group, n = 148); or 4 intradermal injections of low doses (4 ¦Ìg [1/5 of 20

¦Ìg]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (ID4 ¡Á 4 group, n =

144).

MAIN OUTCOME MEASURES: Percentage of responders at week 28, defined as patients

with hepatitis B surface antibody (anti-HBs) of at least 10 mIU/mL in patients

who received at least 1 dose of vaccine. Patients with missing anti-HBs titer

measurement at the final follow-up visit at week 28 were considered as

nonresponders in the primary (efficacy) analysis.

RESULTS: A total of 437 patients were randomized to the 3 study groups, of whom

11 did not receive any vaccine. Of these, 396 had available anti-HBs titers at

week 28. The percentage of responders at week 28 was 65% (95% confidence

interval [CI], 56%-72%) in the IM20 ¡Á 3 group (n = 91), 82% (95% CI, 77%-88%)

in the IM40 ¡Á 4 group (n = 119) (P < .001 vs IM20 ¡Á 3 group), and 77% (95% CI,

69%-84%) in the ID4 ¡Á 4 group (n = 108) (P = .02 vs IM20 ¡Á 3 group). No safety

signal and no effect on CD4 cell count or viral load were observed.

CONCLUSION: In adults with HIV-1, both the 4 intramuscular double-dose regimen

and the 4 intradermal low-dose regimen improved serological response compared

with the standard HBV vaccine regimen.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00480792.

PMID: 21486976 [PubMed - in process]

[Guest guest]

JAMA. 2011 Apr 13;305(14):1432-40.

Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low

doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized

controlled trial.

Launay O, van der Vliet D, Rosenberg AR, Michel ML, Piroth L, Rey D, Colin de

Verdi¨¨re N, Slama L, K, Lortholary O, Carrat F; ANRS HB03 VIHVAC-B

Trial.

Collaborators (71)

Paris Descartes University, France. odile.launay@...

Abstract

CONTEXT: Alternative schedules more immunogenic than the standard hepatitis B

vaccine regimen are needed in patients with human immunodeficiency virus 1

(HIV-1) infection.

OBJECTIVE: To compare the safety and immunogenicity of 4 intramuscular

double-dose and 4 intradermal low-dose regimens vs the standard hepatitis B

vaccine regimen.

DESIGN, SETTING, AND PARTICIPANTS: An open-label, multicenter, 1:1:1

parallel-group, randomized trial conducted between June 28, 2007, and October

23, 2008 (date of last patient visit, July 3, 2009) at 33 centers in France with

patients enrolled in French National Agency for Research on AIDS and Viral

Hepatitis trials in adults with HIV-1 infection who were hepatitis B virus (HBV)

seronegative and having CD4 cell counts of more than 200 cells/¦ÌL.

INTERVENTION: Patients were randomly assigned to receive 3 intramuscular

injections of the standard dose (20 ¦Ìg) of recombinant HBV vaccine at weeks 0,

4, and 24 (IM20 ¡Á 3 group, n = 145); 4 intramuscular double doses (40 ¦Ìg [2

injections of 20 ¦Ìg]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (IM40

¡Á 4 group, n = 148); or 4 intradermal injections of low doses (4 ¦Ìg [1/5 of 20

¦Ìg]) of recombinant HBV vaccine at weeks 0, 4, 8, and 24 (ID4 ¡Á 4 group, n =

144).

MAIN OUTCOME MEASURES: Percentage of responders at week 28, defined as patients

with hepatitis B surface antibody (anti-HBs) of at least 10 mIU/mL in patients

who received at least 1 dose of vaccine. Patients with missing anti-HBs titer

measurement at the final follow-up visit at week 28 were considered as

nonresponders in the primary (efficacy) analysis.

RESULTS: A total of 437 patients were randomized to the 3 study groups, of whom

11 did not receive any vaccine. Of these, 396 had available anti-HBs titers at

week 28. The percentage of responders at week 28 was 65% (95% confidence

interval [CI], 56%-72%) in the IM20 ¡Á 3 group (n = 91), 82% (95% CI, 77%-88%)

in the IM40 ¡Á 4 group (n = 119) (P < .001 vs IM20 ¡Á 3 group), and 77% (95% CI,

69%-84%) in the ID4 ¡Á 4 group (n = 108) (P = .02 vs IM20 ¡Á 3 group). No safety

signal and no effect on CD4 cell count or viral load were observed.

CONCLUSION: In adults with HIV-1, both the 4 intramuscular double-dose regimen

and the 4 intradermal low-dose regimen improved serological response compared

with the standard HBV vaccine regimen.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00480792.

PMID: 21486976 [PubMed - in process]