Stimulating Evidence for Pneumococcal Conjugate Vaccination Among HIV-Infected Adults.

Streptococcus pneumoniae remains a formidable foe—it is the leading cause of bacterial pneumonia and an important cause of invasive disease. Adults infected with human immunodeficiency virus (HIV) are at particular risk for invasive pneumococcal disease (IPD), with an approximate 40-fold risk compared with the general population despite the advent of combination antiretroviral therapy (cART) [1–3]. Furthermore, up to 25% of HIV-infected persons develop recurrent disease, most commonly because of reinfection [4, 5]. The annual IPD incidence of 245 cases per 100 000 among HIVpositive adults in the developed world [2] points to the need for additional modalities to prevent this all too common infection. The burden of pneumococcal disease among adults infected with HIV may be mitigated by several strategies including the use of effective cART, the avoidance of specific modifiable behaviors (eg, smoking, illicit drug use), prophylaxis against Pneumocystis carinii pneumonia (ie, trimethoprim-sulfamethoxazole), and annual influenza vaccination [1, 6, 7]. The most specific intervention to reduce IPD is the use of pneumococcal vaccination [6]. Two types of pneumococcal vaccines currently exist—a pneumococcal polysaccharide vaccine containing 23 serotypes (PPSV23) available since 1983, and pneumococcal conjugate vaccines (PCVs), available since 2000 as a 7-valent (PCV7) and since 2010 as a 13-valent (PCV13) formulation. Given the risk of IPD among HIVinfected persons, vaccine advisory committees have recommended pneumococcal vaccinations since the 1980s [8]. Initially, guidelines advised a single dose of PPSV23 at HIV diagnosis, followed by revaccination at 5 years and then again at age 65 years (assuming ≥5 years had elapsed since last vaccine). Unfortunately, after PPSV23 anti-pneumococcal antibody levels rapidly decline [9], leaving HIV-infected patients at continued substantial risk for IPD [10–12]. More recent guidelines [6, 13–15] have added PCV to the list of recommended vaccines. The recommendation for the use of PCV among HIV-infected adults was supported by data showing that PCV elicits superior immunologic responses [16–21] and convincing results from a randomized, double-blind, placebo-controlled trial of PCV (using the PCV7) among HIV-infected adults in Malawi [22]. The Malawi study found that PCV7 had a 74% efficacy against vaccine-type IPD among HIV-infected adults with a prior history of IPD, with demonstrable efficacy even among those with low CD4 cell counts (<200 cells/mm). Because PCV is an excellent priming vaccine, it is preferably administered as the first pneumococcal vaccine [18, 19, 23], and current guidelines recommend administration of PCV at HIV diagnosis, followed by PPSV23 ≥8 weeks later [6, 13–15]; PPSV23 continues to be recommended given the limited serotype coverage of the currently available conjugate vaccine. Although this may be the ideal sequencing for pneumococcal vaccinations, many HIV-infected adults in care have already received ≥1 dose of PPSV23. Guidelines have suggested that, in this situation, a single dose of PCV13 should be administered ≥1 year after the last PPSV23 [6, 13–15]. However, in immunogenicity studies to date, the value of PCV7 after an initial PPSV23 dose has been mixed [16, 24]. In this issue of the Journal, Glesby et al [25] report a large (n = 329) study of the immunogenicity and safety of PCV13 administered as 3 sequential doses at 6month intervals. The study population consisted of HIV-infected adults who had previously received ≥1 dose of PPSV23 and had a CD4 cell count ≥200 cells/ mm and an HIV RNA level <50 000 copies/mL. Approximately 95% of study Received 6 November 2014; accepted 7 November 2014; electronically published 13 November 2014. Correspondence: Nancy F. Crum-Cianflone, MD, MPH, Scripps Mercy Hospital, 4077 Fifth Ave, San Diego, CA 92103 ([email protected]). The Journal of Infectious Diseases 2015;212:1–4 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jiu632