Browsing by Author "Ayles, Helen M."

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    Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis
    (Massachusetts Medical Society, 2018-10-25) Van der Meeren, Olivier; Hatherill, Mark; Nduba, Videlis; Wilkinson, Robert J.; Muyoyeta, Monde; Van Brakel, Elana; Ayles, Helen M.; Henostroza, German; Thienemann, Friedrich; Scriba, Thomas J.; Diacon, Andreas; Blatner, Gretta L.; Demoitie, Marie-Ange; Tameris, Michele; Malahleha, Mookho; Innes, James C.; Hellstrom, Elizabeth; Martinson, Neil; Singh, Tina; Akite, Elaine J.; Khatoon Azam, Aisha; Bollaerts, Anne; Ginsberg, Ann M.; Evans, Thomas G.; Gillard, Paul; Tait, Dereck R.
    BACKGROUND: A vaccine to interrupt the transmission of tuberculosis is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)–negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette–Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both. RESULTS: We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS: M72/AS01E provided 54.0% protection for M. tuberculosis–infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598. opens in new tab.)
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    ZAMSTAR, The Zambia South Africa TB and HIV Reduction study : design of a 2x2 factorial community randomized trial
    (BioMed Central, 2008-11) Ayles, Helen M.; Sismanidis, Charalambos; Beyers, Nulda; Hayes, Richard J.; Godfrey-Faussett, Peter
    Background: TB and HIV form a deadly synergy in much of the developing world, especially Africa. Interventions to reduce the impact of these diseases at community level are urgently needed. This paper presents the design of a community randomised trial to evaluate the impact of two complex interventions on the prevalence of tuberculosis (TB) in high HIV prevalence settings in Zambia and South Africa. Methods: The interaction between TB and HIV is reviewed and possible interventions that could reduce the prevalence of TB in HIV-endemic populations are discussed. Two of these interventions are described in detail and the design of a 2 × 2 factorial community randomised trial to test these interventions is presented. The limitations and challenges of the design are identified and discussed. Conclusion: There is an urgent need to reduce the prevalence of TB in communities highly affected by HIV. Potential interventions are complex and require innovative trial designs to provide the rigorous evidence needed to inform health policy makers and to ensure that resources are used optimally. Trial Registration Number: ISRCTN36729271