Fast track — ArticlesEfficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial
Introduction
Before the introduction of effective antiretroviral therapy in more-developed countries, survival in HIV-1-infected patients had been improved mainly by prevention of opportunistic infections with antibiotic prophylaxis.1 In Africa, HIV-1-infected patients have not benefitted from such therapies; antiretroviral therapy remains too costly and complex, and antibiotic prophylaxis regimens available in more-developed countries are not directly applicable to African patients because of a different spectrum of opportunistic infections.2 Although Pneumocystis carinii pneumonia is a leading cause of AIDS-related death in more-developed countries, tuberculosis, toxoplasmosis, and bacterial infections are the causes of most deaths and admissions to hospital related to HIV-1 in Côte d'Ivoire.3, 4, 5, 6 Effective regimens exist to prevent tuberculosis,7, 8, 9, 10, 11 but no antibiotic prophylaxis regimens have been assessed for prevention of other opportunistic infections in Africa.
HIV-1-infected patients with tuberculosis represent a large group of patients who might benefit from such regimens. 20–70% of patients with active tuberculosis in Africa are coinfected with HIV-1,12 and mortality among these patients is high, even after tuberculosis is cured.13, 14, 15, 16, 17 In Abidjan, Côte d'Ivoire, for example, the mortality per 100 person-years among patients with tuberculosis and HIV-1 infection was 20·3 compared with 2·2 for patients with tuberculosis alone.18 The reasons for the raised mortality among HIV-1-infected patients with tuberculosis remain unclear, but the low rate of tuberculosis recurrence in some studies and necropsy data suggest that this increased mortality may be due largely to other opportunistic infections rather than to a recurrence of tuberculosis.19
In addition to these considerations, data from Abidjan suggest that, after tuberculosis, the most common opportunistic infections—salmonellosis, isosporiasis, cerebral toxoplasmosis, and bacterial pneumonia3, 4, 5—might be prevented by administration of trimethoprim-sulphamethoxazole (co-trimoxazole), and that most of the pathogens that cause fatal sepsis are sensitive to co-trimoxazole.20 We did a randomised placebo-controlled trial to assess whether daily co-trimoxazole prophylaxis could prevent opportunistic infections and thereby decrease morbidity and mortality among HIV-1-infected patients with tuberculosis in Abidjan.
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Patients and methods
The study was approved by the institutional review board of the Centers for Disease Control and Prevention in Atlanta, Georgia, USA, and the ethics committees of the Côte d'Ivoire Ministry of Health and the London School of Hygiene and Tropical Medicine, London, UK.
Results
Enrolment began in October, 1995, and ended on April 8, 1998, after the results of an independent co-trimoxazole prophylaxis trial were released.27 On April 14, 1998, based on a review of the available results, and since it was thought no longer ethical to continue to enrol new patients, the data and safety monitoring board recommended suspension of enrolment. After discussions with the Côte d'Ivoire Ministry of Health, enrolment was stopped and all study patients received open-label
Discussion
We have shown that the daily administration of co-trimoxazole can lower by almost half the rates of death and admission to hospital among HIV-1-infected tuberculosis patients in Abidjan. Analysis of the causes of admission show that the co-trimoxazole regimen prevented enteritis and septicaemia and was possibly effective against urinary-tract infections and cerebral toxoplasmosis. Given the large number of HIV-1-infected patients with tuberculosis throughout Africa and the high mortality they
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