Immunogenicity of pneumococcal vaccination in HIV infected individuals: A systematic review and meta-analysis

Abstract

Background The objective of this systematic review and meta-analysis was to summarise the literature regarding the immunogenicity of pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPSV) in adult people living with HIV (PLWH) in the era of advanced combination antiretroviral therapy (cART). Methods The systematic review protocol was published online (PROSPERO ID: CRD 42020153137). We searched Medline (Ovid), EMBASE (Ovid), and the Global Health Library for publications from 2000 to June 11, 2020. We included all studies in adult PLWH that reported vaccine immunogenicity outcomes. The primary outcome was seroconversion rate (SCR) after PCV, PPSV and PCV/PPSV combined. For random-effects meta-analysis, we included studies defining SCR as a ≥ 2-fold increase in IgG from baseline, and reporting SCR for serotypes 6B, 14, or overall SCR, 1–3 months after vaccination. Findings Our search identified 1597 unique studies, of which 115 were eligible for full-text assessment. Of these, 39 met the inclusion criteria (11 RCTs; 28 cohort studies). A high degree of heterogeneity was observed. Nineteen studies were included in the meta-analysis. Pooled overall SCRs were 42% (95% CI 30–56%), 44% (95% CI 33–55%) and 57% (95% CI 50–63%) for PLWH who received PPSV, PCV or a combination of PCV/PPSV, respectively. Compared to PPSV alone, a combination of PCV/PPSV yielded higher SCRs (OR 2.24 95% CI 1.41- 3.58), whereas we did not observe a significant difference in SCR between PCV and PPSV23 alone. There were no statistically significant differences in geometric mean post-vaccination antibody concentrations between vaccination schedules. Vaccination at higher CD4 cell counts improved immunogenicity in 8/21 studies, especially when PCV was administered. No studies assessed the long-term immunogenicity of PCV followed by PPSV23. Quality of evidence ranged from poor ( n = 19) to good quality ( n = 7). A limited number of pneumococcal serotypes was assessed in the majority of studies. Interpretation We show that the recommended immunisation schedule consisting of a combination of PCV13/PPSV23, is immunogenic in PLWH in the era of advanced cART. However, the durability of this vaccination schedule remains unknown and must be addressed in future research. Vaccination with PCV should be delayed until immunological recovery (CD4>200) in recently diagnosed PLWH for optimal immunogenicity. The evidence gathered here supports wide implementation of the combination of PCV/PPSV23 for all PLWH. We recommend reassessment of this strategy once higher-valent PCVs become available. Funding HMGG is funded by a public research grant of ZonMw (project number 522004005).

Pneumococcal Vaccination in Immunocompromised Hosts: An Update

“…There is an additional increase in recurrent invasive infections post treatment of pneumococcal disease [ 23 ]. This has reduced significantly following the advent of combined ART [ 24 ], however this incidence remains elevated in HIV populations when compared to a general population [ 25 ]. Risk factors for invasive pneumococcal disease within the HIV population include ethnicity, CD 4 count (200–499 cells/mL), intravenous drug and excess alcohol use, a smoking history and chronic liver disease [ 26 , 27 ].…”

“…Although evidence is lacking, the current UK recommendation is for sequential vaccination with PCV13 followed by PPV23 to induce and maintain protective immunity [ 30 ]. There is growing evidence to delay PCV13 vaccination until after recovery of CD4 T cell count (>200 cells/mm 3 ) due to the immunology of T- cell dependent versus T- cell independent vaccines [ 24 ]. As treatment with cART improves longevity in the HIV population, further studies are needed to examine the durability of the immune response against pneumococcal disease.…”

Single-Dose 13-Valent Conjugate Pneumococcal Vaccine in People Living With HIV – Immunological Response and Protection

“…An initial PCV13 is currently recommended for all PLHIV, followed in most guidelines by a PPV23 vaccine at least 2 months later to broaden serotype coverage (7)(8)(9)16). The clinical efficacy of this combined vaccination schedule in PLHIV is unknown (17).…”

“…Data are scarce concerning the immunological response to PCV13 vaccine among PLHIV, leading to a low overall pneumococcal vaccine coverage in this population (17).…”

Pneumococcal vaccination in persons living with HIV: Pneumococcal conjugate, polysaccharide or both?

“…In EClinicalMedicine, the systematic review and meta-analysis by Abraham Goorhuis et al [8] looks into the available literature on immunogenicity of pneumococcal vaccination in PLWH, after combination ART became available in 2000 [9]. It is interesting that out of 1597 study unique studies only 19 could be included for the final meta-analysis.…”