Pneumococcal Conjugate Vaccine Is Effective in HIV-infected Patients
Abstract and Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.
Synopsis: In this study, 496 adults and adolescents (88% of whom were HIV-infected) who had recovered from invasive pneumococcal disease were administered a seven-valent pneumococcal conjugate vaccine (PCV7) in a double-blind, randomized, placebo-controlled trial. All subsequent episodes of pneumococcal disease occurred in HIV-infected patients. Twenty-four episodes of pneumococcal disease were observed with vaccine serotypes or serotype 6A. Of these, five occurred in the vaccine group and 19 in the placebo group, yielding a vaccine efficacy rate of 74%.
Source: French N, et al. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med. 2010;362: 812-822.
In this study, 496 adults and adolescents in Malawi, with history of recent documented invasive pneumococcal disease, were administered PCV7 or placebo in a randomized, double-blind, controlled trial, and were followed for 798 person-years. Eighty-eight percent of patients were HIV-infected. During follow-up, 67 new episodes of pneumococcal disease were seen in 52 patients, all of whom were HIV-infected. In 24 patients, 19 episodes of disease due to vaccine serotypes and five episodes due to serotype 6A were observed, yielding a vaccine efficacy of 74%. Overall mortality included 73 deaths due to all causes in the placebo group vs. 63 deaths in the vaccine group. PCV7 was well tolerated, with only minor vaccine-associated adverse events seen.
The risk of invasive pneumococcal disease is greatly elevated in HIV-infected patients, and may be as high as 30-100 times as high as in age-matched controls. The 23-valent pneumococcal polysaccharide vaccine has limited efficacy in HIV-infected patients, particularly in those with lower CD4+ lymphocyte counts, and its use is not recommended in Africa. PCV7 has been widely used in children in the developed world since 2000, and has markedly reduced the incidence of invasive pneumococcal disease in children and in adults (the latter presumably related to herd immunity). Since recurrent invasive pneumococcal disease is common in HIV-infected patients, a smaller sample size to demonstrate efficacy was needed when evaluating vaccine efficacy in patients who had already had one episode of invasive pneumococcal disease.
The demonstrated efficacy of PCV7 in HIV-infected patients in this trial is good news. The patients evaluated in this trial had fairly advanced disease, with a median CD4+ count of 212-214/uL. While PCV7 had good efficacy vs. vaccine serotypes (and serotype 6A, since PCV7 was shown in earlier studies to provide cross-protection against this serotype), it had no effect vs. non-vaccine serotypes. Recognition of invasive disease in immunocompetent children due to nonvaccine serotypes has increased over the last few years. A new 13-valent PCV is expected to receive FDA approval shortly, and will provide protection against many of these serotypes, including serotype 19A, which often displays antibiotic resistance.
Parenthetically, Malawi is an interesting place. It is very poor in natural resources. It is not part of the PEPFAR program. However, some NGOs are doing excellent work there treating both TB and HIV. One of the best of these is an organization known as GAIA (Global AIDS Interfaith Alliance, www.thegaia.org), headquartered here in San Francisco, and founded by the Rt. Rev. Bill Rankin, retired Dean of the Episcopal Church Divinity School of the Pacific seminary in Berkeley. In addition to providing antiretroviral therapy and TB treatment, a big part of their work is empowering women in villages in Malawi, including providing microloans so they can start small businesses.