Elsevier

The Lancet

Volume 355, Issue 9221, 17 June 2000, Pages 2106-2111
The Lancet

Articles
23–valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial

https://doi.org/10.1016/S0140-6736(00)02377-1Get rights and content

Summary

Background

Infection with Streptococcus pneumoniae is a frequent and serious problem for HIV-immunosuppressed adults. Vaccination is recommended in the USA and Europe, but there are no prospective data that show vaccine efficacy.

Methods

1392 (937 female) HIV-1-infected adults in Entebbe, Uganda, were enrolled. 697 received 23-valent pneumococcal polysaccharide vaccine and 695 received placebo. The primary endpoint was first event invasive pneumococcal disease. Secondary endpoints included vaccine serogroup-specific invasive disease, all (probable and definite) pneumococcal events, all-cause pneumonia, and death.

Findings

First invasive events occurred in 25 individuals (24 bacteraemias, one pyomyositis), 15 in the vaccine arm and ten in the placebo arm (hazard ratio [HR] 1·47; 95% CI 0·7–3·3). 22 isolates (88%) were of vaccine-specific serogroups with 15 events in the vaccine arm compared with seven in the placebo arm (HR 2·10; 0·9–5·2). All pneumococcal events had a similar distribution (20 vs 14; HR 1·41; 0·7–2·8) though all-cause pneumonia was significantly more frequent in the vaccine arm (40 vs 21; HR 1·89; 1·1–3·2). Mortality was unaffected by vaccination.

Interpretation

23-valent pneumococcal polysaccharide vaccination is ineffective in HIV-1-infected Ugandan adults and probably has little, or no, public health value elsewhere in sub-Saharan Africa. Increased rates of pneumococcal disease in vaccine recipients may necessitate a reappraisal of this intervention in other settings.

Introduction

Streptococcus pneumoniae is a frequent and serious infection in HIV-1-infected adults in Africa,1 North America2 and Europe.3 It is the most important potentially vaccine-preventable, HIV-1-associated pathogen. The 23-valent pneumococcal polysaccharide vaccine has been recommended in the USA since 19894 and UK since 19925 on the basis of few immunogenicity data,6 modest cost of the intervention, and assumptions that the vaccine was safe and well tolerated. No efficacy data supported these recommendations.

Immunisation has become standard of care in industrialised countries;7 30–40% of HIV-infected adults in the USA (over 300 000) are estimated to have been immunised.8 Retrospective case-control studies have suggested some benefit,9 and immunogenicity data confirm serological response to the polysaccharides in the vaccine in HIV-infected recipients, but at a lower level than in immunocompetent adults.6, 10, 11 High rates of invasive pneumococcal disease in African countries, and attributable morbidity and mortality,2, 12 make this a prime target for prevention by immunisation. However, because of limited health care resources, widespread immunisation of HIV-infected African adults would be unjustifiable without proof of clinical efficacy of the polyvalent polysaccharide vaccine.13

Studies from Kenya recorded the risk of invasive pneumococcal disease with HIV-related immuno-suppression,1 and showed that pneumococcal polysaccharide was immunogenic.10 Moreover, immunisation had the potential to be an appropriate and cost-effective public health intervention for HIV-infected adults in this region. A pilot study in Entebbe, Uganda, confirmed immunogenicity of the vaccine and verified that an appropriate cohort of HIV-infected adults could be recruited and followed for a clinical efficacy trial.11 Subsequently a randomised, placebo-controlled trial of 23-valent pneumococcal polysaccharide vaccine (PnuImmune, Wyeth-Lederle, Pearl River, New York, USA) was initiated and we now report the results of this work.

Section snippets

Clinical and field methods

The study was done in two community-based HIV care clinics (The AIDS Support Organisation of Uganda, TASO; and the Ministry of Health clinic, Uganda Virus Research Institute) providing HIV testing, counselling and outpatient medical services to HIV-1 infected residents of Entebbe, Uganda.

HIV-1-infected adults (age 15 years or older) in WHO clinical stage 1, 2, or 314 and living within 15 km of the study clinics were invited to take part in a double-blind randomised placebo controlled trial with

Results

Between October, 1995 and June,1998, 1392 adults were enrolled into the trial. 69 individuals were excluded from analysis for protocol violations (figure 1). Randomisation was successful for the remaining 1323 participants with baseline demographic characteristics of the vaccine and placebo recipients well matched (table 1).

The vaccine was well tolerated. In the first 2 weeks after enrolment, deaths occurred in two vaccine and two placebo recipients (0·3% of participants). Review by the

Discussion

Pneumococcal vaccines have been recommended as a standard of care for HIV-infected adults in North America and UK, 4, 5 but are of unknown efficacy. Because invasive pneumococcal disease is particularly prevalent in sub-Saharan Africa, 1, 12 and immunisation has been proposed as a strategy to reduce the burden of HIV-associated disease,13 we did a randomised controlled trial of pneumococcal polysaccharide vaccine in HIV-1-infected adults in Uganda. Our results suggest that immunisation is

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