A Randomized Clinical Trial Comparing Revaccination with Pneumococcal Conjugate Vaccine to Polysaccharide Vaccine among HIV‐Infected Adults

Abstract

Background The risk of pneumococcal disease persists and antibody responses to revaccination with the 23-valent polysaccharide vaccine (PPV) are low among HIV-infected adults. We determined whether revaccination with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these responses. Methods In a randomized clinical trial, we compared the immunogenicity of revaccination with PCV (n=131) or PPV (n=73) among HIV-infected adults (median CD4 count 533 cells/mm3) vaccinated with PPV 3–8 years earlier. HIV-uninfected adults (n=25) without prior pneumococcal vaccination received one dose of PCV. A positive response was defined as a ≥2-fold rise (baseline to day 60) in capsule-specific IgG with a post-vaccination level value ≥1000 ng/ml for at least 2 of the 4 serotypes. Results HIV-infected persons demonstrated a higher frequency of positive antibody responses to PCV vs. PPV (57% vs. 36%, p=0.004) and greater IgG concentration mean changes from baseline to day 60 for serotypes 4, 9V, and 19F (all p<0.05), but not for serotype 14. However by day 180 both outcomes were similar. Responses to PCV were greater in frequency and magnitude for all serotypes in HIV-uninfected compared with those in HIV-infected adults. Conclusions Among persons with HIV infection, revaccination with PCV was only transiently more immunogenic than PPV, and responses were inferior to those in HIV-uninfected subjects with primary vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity are needed for HIV-infected adults.

Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

“…Revaccination with 2 doses of PCV7 resulted in a higher immune response rate to at least 2 of the 4 serotypes assessed compared to revaccination with one dose of PCV7 or PPV23 throughout week 12 to week 48. 41 The conflicting results between the 2 studies may be due to different serotypes assessed and lower baseline antibody levels among patients in the former study, 56 which may decrease the proportion of the participants who could achieve post-vaccination antibody levels to 1 mg/ml.…”

“…Efficacy, immunogenicity and safety of PCVs in the HIVinfected individuals were recently reviewed by Nunes and Madhi 51 and Cordonnier et al 52 Published studies to examine the immunogenicity of PCVs in the HIV-infected adults using different strategies are updated in Table 2 33, 35,36,[39][40][41][39][40][41][53][54][55][56][57][58][59][60][61] Similar to those observed in the immunogenicity studies of PPV23, direct comparisons between these studies and attempts to draw conclusions are confounded by the fact that the studies are heterogeneous in the vaccination schedule adopted (PCV alone or prime-boost vaccination with PCV followed by PPV, vaccine dose and interval between 2 vaccinations), time point of assessing serological response, the definitions used for serological responses ( Table 2). While the correlation between the serological responses and clinical protection against IPD for adults is lacking, the antibody threshold used to define immune response in these studies is either 0.35 mg/ml or 1 mg/ml.…”

“…38 Therefore, several studies have examined the immunogenicity of revaccination with PCV in HIV-infected patients who have received PPV before. 41,54,56 The first study in Uganda by Miiro et al compared the immunogenicity of 2 doses of PCV7 (4 weeks apart) versus placebo in HIV-infected adults who have received PPV23 3.5 to 6.6 y (median 5.2 years) earlier. 54 Significant increases in antibody concentrations to all vaccine serotypes were observed after revaccination with PCV7, but no difference in immune response was found by past vaccination status, suggesting that past receipt of PPV23 did not blunt the immune response to PCV7.…”

“…54 In the randomized trial by Crum-Cianflone et al, vaccination with PCV7 in HIV-infected adults who had previously received PPV23 3 to 8 y earlier (median 4.6 years) temporarily induced a better immune response than PPV23 at 14 and 60 d after vaccination, but this effect did not sustain to 180 d post-vaccination. 56 In another observational study by Lu et al, one or 2 doses of PCV7 (4 weeks apart) or PPV23 were administered in HIV-infected adults previously vaccinated with PPV23 5 y or more earlier. Revaccination with 2 doses of PCV7 resulted in a higher immune response rate to at least 2 of the 4 serotypes assessed compared to revaccination with one dose of PCV7 or PPV23 throughout week 12 to week 48.…”

Association of CMV, HBV, or HCV co-infection with vaccine response in adults with well-controlled HIV infection

“…Although this improves with cART and CD4 count recovery, the vaccine response in HIV-infected adults with CD4 counts in the normal range remains lower than in uninfected individuals. [4][5][6] For example, 80% of HIV-infected adults with CD4 counts >500 cells/mm 3 achieved seroprotection against hepatitis A virus (HAV) after a 2-dose HAV vaccine series, versus >94% of the general population. 7,8 Likewise, 59% of HIV-infected adults with CD4 counts >500 cells/mm 3 responded to the H1N1 vaccine, vs. 80% of uninfected adults.…”