Elsevier

The Lancet

Volume 353, Issue 9163, 1 May 1999, Pages 1463-1468
The Lancet

Articles
Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial

https://doi.org/10.1016/S0140-6736(98)07399-1Get rights and content

Summary

Background

In sub-Saharan Africa, various bacterial diseases occur before pneumocystosis or toxoplasmosis in the course of HIV-1 infection, and are major causes of morbidity and mortality. We did a randomised, double blind, placebo-controlled clinical trial at community-health centres in Abidjan, Côte d'Ivoire, to assess the efficacy of trimethoprim-sulphamethoxazole (co-trimoxazole) chemoprophylaxis at early stages of HIV-1 infection.

Methods

843 HIV-infected patients were screened and 545 enrolled in the study. Eligible adults (with HIV-1 or HIV-1 and HIV-2 dual seropositivity at stages 2 or 3 of the WHO staging system) received co-trimoxazole chemoprophylaxis (trimethoprim 160 mg, sulphamethoxazole 800 mg) daily or a matching placebo. The primary outcome was the occurrence of severe clinical events, defined as death or hospital admission irrespective of the cause. Analyses were by intention to treat.

Findings

Four of the randomised patients were excluded (positive for HIV-2 only). 120 severe events occurred among 271 patients in the co-trimoxazole group and 198 among 270 in the placebo group. Significantly fewer patients in the co-trimoxazole group than in the placebo group had at least one severe event (84 vs 124); the probability of remaining free of severe events was 63·7% versus 45·8% (hazard ratio 0·57 [95% CI 0·43–0·75], p=0·0001) and the benefit was apparent in all subgroups of initial CD4-cell count. Survival did not differ between the groups (41 vs 46 deaths, p=0·51). Co-trimoxazole was generally well tolerated though moderate neutropenia occurred in 62 patients (vs 26 in the placebo group).

Interpretation

Patients who might benefit from co-trimoxazole could be recruited on clinical criteria in community clinics without knowing the patients CD4-cell count. This affordable measure will enable quick public-health intervention, while monitoring bacterial susceptibility and haematological tolerance.

Introduction

By the end of 1997, the United Nations' AIDS programme and the WHO estimated that 20·8 million adults were infected with HIV in sub-Saharan Africa.1 In Abidjan, Côte d'Ivoire, AIDS is the leading cause of adult death.2 In this large urban centre of West Africa, the prevalence of HIV infection has been estimated at 20% in adults attending outpatient services of community health centres,3 and more than 50% in many hospital departments.4 In Abidjan, where both HIV-1 and HIV-2 are present, more than 90% of HIV-infected people are infected with HIV-1, with or without HIV-2 coinfection.4 Public-health measures aim to improve the quality of life of HIV-1-infected patients, and to decrease the number of patients presenting with opportunistic infections.

Prevention of opportunistic infections could provide both individual and public-health benefits. However, international guidelines on HIV are difficult to tailor to the African environment, because of: the limited resources of HIV-1-infected people and health-care infrastructures; the different range of disease associated with HIV-1, including the overwhelming burden of tuberculosis as the primary cause of mortality and the low prevalence of Pneumocystis carinii infection;5, 6, 7 and the difficulty in basing chemoprophylaxis recommendations on a threshold of CD4-cell count when cell counting is not routinely available.8

Various bacterial and parasitic pathogens (other than Pneumocystis carinii) such as salmonella other than Salmonella typhi, Streptococcus pneumoniae, Toxoplasma gondii, and Isospora belli, are major nontuberculous causes of HIV-1-related morbidity in Africa.5, 9, 10, 11, 12 Trimethoprim-sulphamethoxazole (co-trimoxazole) prevents toxoplasmosis13 and isosporiasis,14 and might protect against HIV-1-related bacterial diseases,15, 16, 17, 18 which have a higher incidence in Africa than in industrialised countries,6 and occur at an earlier stage of HIV-1 immunosuppression than pneumocystis or toxoplasma infections.16, 19

We assessed the efficacy of co-trimoxazole prophylaxis in decreasing the occurrence of severe clinical events in African adults seropositive for HIV-1 at early stages of HIV-1 infection.

Section snippets

Patients

Our study was a randomised, placebo-controlled clinical trial, based on patients attending five community clinics in Yopougon, a district area of Abidjan, Côte d'Ivoire. The study protocol was approved by the ethics committees of both the national ivoirian programme on AIDS and the Bordeaux University Hospital in France, and the institutional review board of the French Agency of Research on AIDS (ANRS).

Between April 23, 1996, and March 17, 1998, HIV-infected adults aged 18 years and over, were

Results

843 HIV-infected patients were screened at the trial centre, and 545 were enrolled in the trial and randomly assigned to treatment (figure 1). The remaining 298 patients were not eligible: 12 were positive for HIV-2 only; eight were pregnant or lactating; 119 did not return; 29 lived outside Abidjan; six had a history of intolerance to sulphonamide; one had renal failure; two had haemoglobin less than 7 g/dL; 31 were WHO stage 1; and 90 were WHO stage 4. Among the 90 stage 4 patients, the two

Discussion

We found that the rate of severe events leading to death or hospital admission in African adults at clinical stage 2 and 3 of the WHO staging system20 was 43% lower with co-trimoxazole than with placebo. The occurrence of death or hospital admission was chosen as a primary outcome because: co-trimoxazole is likely to prevent many infectious diseases, thus, its efficacy had to be assessed on broad criteria; and hospital admission and death reflect the burden of opportunistic infections on both

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