A Trial of a 7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults

N Engl J of Medicine March 4, 2010  V.362  N.9  p.812-822

Neil French, Ph.D., F.R.C.P., Stephen B. Gordon, M.D., F.R.C.P., Thandie Mwalukomo, M.B., B.S., Sarah A. White, Ph.D., Gershom Mwafulirwa, Dip.Med.Sci., Herbert Longwe, M.Phil., Martin Mwaiponya, M.B., B.S., Eduard E. Zijlstra, M.D., Ph.D., Malcolm E. Molyneux, M.D., F.R.C.P., and Charles F. Gilks, D.Phil., F.R.C.P.

ABSTRACT

Background

Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed.

Methods

In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A.

Results

From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P=0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P=0.003).

Conclusions

The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731 [controlled-trials.com] .)

abstract

http://content.nejm.org/cgi/content/short/362/9/812?query=TOC

PDF

http://content.nejm.org/cgi/reprint/362/9/812.pdf