A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults.
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.)
French
Neil
N
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. neil.french@lshtm.ac.uk
Gordon
Stephen B
SB
Mwalukomo
Thandie
T
White
Sarah A
SA
Mwafulirwa
Gershom
G
Longwe
Herbert
H
Mwaiponya
Martin
M
Zijlstra
Eduard E
EE
Molyneux
Malcolm E
ME
Gilks
Charles F
CF
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications*; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D022242:Pneumococcal Vaccines / Q000009:adverse effects; D011018:Pneumonia, Pneumococcal / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D012307:Risk Factors; D013296:Streptococcus pneumoniae / Q000145:classification; D018074:Vaccines, Conjugate; D055815:Young Adult
D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate