Articles23–valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial
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.
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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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2020, EClinicalMedicineCitation Excerpt :In adults, no studies of good quality have been conducted on clinical efficacy of pneumococcal vaccines in PLWH on cART [69]. The only RCTs available were performed in sub-Sahara Africa in predominantly untreated HIV patients and with poor immunological status [70,71]. To establish scientific proof of clinical vaccine efficacy against pneumococcal disease, large sample sizes are required, which, for PLWH, do not seem realistic to achieve [10].