A 5‐year longitudinal follow‐up study of serological responses to 23‐valent pneumococcal polysaccharide vaccination among patients with HIV infection who received highly active antiretroviral therapy^*

Abstract

BackgroundLong-term antibody responses to 23-valent pneumococcal polysaccharide vaccine (PPV) among HIV-infected patients receiving highly active antiretroviral therapy (HAART) are rarely investigated. MethodsAntibody responses to three pneumococcal capsular polysaccharides [Pneumococcal polysaccharide (PPS) 14, 19F and 23F] were assessed among 169 HIV-infected patients who received HAART and 23-valent PPV. Patients were stratified into four groups according to CD4 count at vaccination: group 1, CD4o100 cells/mL (n 5 35); group 2, CD4 100-199 cells/mL (n 5 36); group 3, CD4 200-349 cells/mL (n 5 34); and group 4, CD4 ! 350 cells/mL (n 5 64). The proportion of patients who achieved increases in antibody titres of twofold or greater from baseline values (responders) was compared among the four groups of patients for five consecutive years after vaccination. ResultsThe proportion of responders to the three serotypes was significantly lower among patients in group 1 compared with those in the other three groups during yearly follow-up. Much faster loss of antibody responses was observed in group 1, although the rate of decline varied with the serotypes studied in the four groups. Compared with the nonresponders, more responders had CD4 counts 4100 cells/mL at vaccination and achieved better virological suppression throughout the 5-year period, while the absolute increases of CD4 cell counts after HAART were not statistically significantly different. ConclusionsDespite continued increases in CD4 cell counts after HAART, the proportion of HIV-infected patients who maintained antibody responses to PPV declined significantly over the 5-year follow-up period, especially among those who had CD4 counts o100 cells/mL at vaccination and who failed to achieve virological suppression. DOI: 10.1111/j.1468-1293.2009.00744.x HIV Medicine (2010 r 2009 British HIV Association 54 antiretroviral therapy (HAART) [1]. Although cohort or population-based surveillance studies suggest that the incidence of invasive pneumococcal infections or pneumococcal pneumonia declines among HIV-infected patients with access to HAART and appropriate antimicrobial prophylaxis [2,4,6,7], it remains significantly higher among HIV-infected patients than in the general population, with risk ratios ranging from 35 to 60 [2][3][4]. In observational studies conducted in several developed countries, vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) has been shown to decrease the risk of invasive pneumococcal infections among HIVinfected patients [5,[8][9][10][11][12]. According to U.S. Public Health Service/Infectious Diseases Society of America (USPHS/ IDSA) guidelines, it is recommended that patients with HIV infection who have CD4 lymphocyte counts of 4200 cells/mL should receive 23-valent PPV, and revaccination can be considered for those patients who have initial CD4 counts of o200 cells/mL and whose CD4 counts increase to ! 200 cells/mL after receipt of HAART and for those patients who have undergone pneumococcal polysaccharide v...

Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy

“…[5][6][7] Moreover, the only randomized clinical trial of vaccination with 23-valent PPV among HIV-infected Ugandan adults without receiving cART did not demonstrate clinical benefits in subjects who received 23-valent PPV compared with those who received placebo. 8 The widespread use of pneumococcal conjugate vaccine (PCV) since its licensure has significantly reduced the incidence of invasive pneumococcal disease both in HIV-uninfected and HIV-infected children.…”

Immunization of HIV-infected adult patients — French recommendations

“…32 The loss of the antibodies induced by the nonconjugated polysaccharide vaccine occurs particularly rapidly in the most severely immunocompromised patients or in patients not (Continued on next page) virologically controlled by cART. 33 Conjugated vaccines induce higher immunogenicity and have been tested in HIV-infected patients. A randomized double-blind placebo-controlled clinical trial in HIV-infected adults conducted in Malawi demonstrated the efficacy of 2 doses of the 7-valent conjugate vaccine, which reduced invasive pneumococcal infections by 74% in secondary prophylaxis.…”

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

“…62 Significant decline in immune responses was observed in HIV-infected patients receiving cART 5 y after primary vaccination with PPV23, especially in patients with CD4 <100 cells/ml and uncontrolled HIV replication. 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.…”

“…Despite the limitations by the heterogeneity of study design and execution of these observational studies, the authors concluded that currently available evidence is only moderate to support the routine use of PPV23 in HIV-infected patients and newer or more immunogenic vaccines are needed. 8 With respect to immunogenicity of PPV23, the results of published studies are summarized in Table 1, [31][32][33][34][35][36][37][38][39][40][41] which are much more difficult to interpret than the clinical effectiveness studies because of differences in study design, comparators enrolled, CD4 counts and receipt of antiretroviral therapy, especially cART, of the subjects, pneumococcal serotypes assessed, timing of blood sampling, follow-up duration, methods to assess the response (enzyme-linked immunosorbent assay [ELISA] or opsonophagocytic activity [OPA] assay), definitions used for immune response (fold rise of antibody, antibody concentration, or geometric mean concentration or titer). Despite the renumeration of CD4 counts with cART, several studies have shown that most patients failed to maintain durable antibody response for most serotypes following vaccination with PPV23 over the 5-year follow-up period, especially those who had low CD4 counts at vaccination and uncontrolled HIV replication.…”

“…Despite the renumeration of CD4 counts with cART, several studies have shown that most patients failed to maintain durable antibody response for most serotypes following vaccination with PPV23 over the 5-year follow-up period, especially those who had low CD4 counts at vaccination and uncontrolled HIV replication. 38,42,43 Moreover, in HIV-infected patients receiving long-term cART who had received primary vaccination with PPV23 5 y earlier, revaccination with PPV23 elicited significantly poorer antibody responses than revaccination with one or 2 doses of 7-valent pneumococcal conjugate vaccines (PCV7). 41 Pneumococcal conjugate vaccines (PCVs), wherein conjugation of the capsular polysaccharide to a protein carrier converts the polysaccharide into a T cell-dependent antigen, have been shown to protect against IPD in HIV-infected children 44 and recurrent IPD in HIV-infected Malawian adolescents and adults.…”