Cotrimoxazole prophylaxis for opportunistic infections in adults with HIV: Cochrane systematic review
Assessed as up to date: 2003/03/24
The prevention and early treatment of infections are the mainstay of the medical management of the majority of people with HIV infection, who live in low income countries without access to antiretroviral drugs. Cotrimoxazole is cheap and effective against a wide range of organisms. However, routine prophylactic treatment is difficult to deliver in low-resource settings, and could also lead to increased resistance to the drug.Objectives
To assess the effects of routinely administered cotrimoxazole on death and illness episodes in HIV infected adults.Search methods
We searched the Cochrane HIV/AIDS Group register, the Cochrane Controlled Trials Register, MEDLINE, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and tuberculosis (TB) conferences (search date July 2001). We checked reference lists for trials and other pertinent articles, and contacted pharmaceutical companies and experts in the field.Selection criteria
Randomised or quasi randomised trials comparing routinely administered cotrimoxazole versus placebo or no treatment in adults (age greater than 13 years).Data collection and analysis
Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear trial authors were contacted for further details.Main results
Four trials involving 1476 people were identified. Three trials (1416 people) studied heterosexual men and women in West Africa. A fourth trial was of homosexual men on chemotherapy for Kaposi's sarcoma, in the United States. Meta-analysis of the three African trials showed a significant beneficial effect of cotrimoxazole for death: relative risk 0.69 (95% confidence interval 0.55 to 0.87); for morbid events: 0.76 (0.64 to 0.9); and for hospitalisation: 0.66 (0.48 to 0.92). There was no significantly greater risk of adverse effects: relative risk 1.28 (0.47 to 3.51). Effects were similar in people with early and advanced HIV disease. Insufficient evidence was found on effects in areas with higher bacterial resistance or in people on antiretroviral therapy.Authors' conclusions
In the trials included in the review, cotrimoxazole prophylaxis had a beneficial effect in preventing death and illness episodes in adults with both early and advanced HIV disease. However, the wider applicability of these findings is unclear, in particular to areas with higher background bacterial resistance to cotrimoxazole. Further trials would be required in differing settings to widen applicability.
Grimwade Kate, Swingler George H
A daily low dose of cotrimoxazole for preventing opportunistic infections in adults with HIV
Cotrimoxazole helps to prevent infections in adults who are HIV-infected but may increase resistance to the drug and more trials are needed.
Human immunodeficiency virus (HIV) attacks the immune system, leaving people vulnerable to infections. Such infections often cause death or serious complications. Anti-viral drugs can slow HIV. However, most HIV-infected people live in developing countries without access to these treatments. Preventing infections is therefore the main aim of HIV treatment in developing countries. A daily low dose of cotrimoxazole , an antibiotic (a drug that fights bacterial infections), is used to try to prevent infections and improve survival, but with unknown effectiveness for HIV-infected people. The review found cotrimoxazole improved survival in some areas of Africa and found improvements in other outcomes, but adverse effects and possible drug resistance are unclear. More trials are needed.
Implications for practice
Cotrimoxazole prophylaxis appears to be effective in preventing death and illness episodes in adults with HIV infection. Similar benefit was seen in both early and advanced HIV disease. Insufficient evidence exists of the effect of cotrimoxazole in areas with high bacterial resistance, in people without tuberculosis, and in people on antiretroviral therapy. This lack of evidence should be kept in mind when balancing the beneficial effects of cotrimoxazole against the cost and feasibility of implementation in specific settings and against the potential for the development of bacterial resistance.
Implications for research
Further evidence is needed on the effect of cotrimoxazole prophylaxis in areas of high bacterial resistance, in people without tuberculosis, and in people on antiretroviral therapy. Objections to such trials, on ethical grounds, need to be weighed against the lack of evidence in the above mentioned sub-groups, in which meaningful harmful effects have not been excluded.
Given the limited resources available for any intervention in low income countries, there is also a need to evaluate the cost-effectiveness of this intervention against other potentially cheap interventions in such settings.
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