Efficacy 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.

Abstract

BACKGROUND:

There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality.

METHODS:

Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital.

FINDINGS:

Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group.

INTERPRETATION:

In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

• Authors: S Z Wiktor, M Sassan-Morokro, A D Grant, L Abouya, J M Karon, C Maurice, G Djomand, A Ackah, K Domoua, A Kadio, A Yapi, P Combe, O Tossou, T H Roels, E M Lackritz, D Coulibaly, K M De Cock, I M Coulibaly, A E Greenberg
• Journal: Lancet (London, England) (Lancet) Vol. 353 Issue 9163 Pg. 1469-75 (May 01 1999) ISSN: 0140-6736 [Print] England
• PMID: 10232312 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Infective Agents
• Trimethoprim, Sulfamethoxazole Drug Combination

Topics

• AIDS-Related Opportunistic Infections (drug therapy, epidemiology, prevention & control)
• Adolescent
• Adult
• Anti-Infective Agents (therapeutic use)
• CD4 Lymphocyte Count
• Cote d'Ivoire (epidemiology)
• Female
• Follow-Up Studies
• HIV Infections (drug therapy, mortality)
• HIV-1
• HIV-2
• Hospitalization (statistics & numerical data)
• Humans
• Incidence
• Male
• Middle Aged
• Survival Analysis
• Trimethoprim, Sulfamethoxazole Drug Combination (therapeutic use)
• Tuberculosis (drug therapy, epidemiology, mortality)