Cotrimoxazole prophylaxis for opportunistic infections in children with HIV infection: Cochrane systematic review

Abstract

Assessed as up to date: 2005/09/25

Background

The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic infections are the mainstay of their medical management. Cotrimoxazole is cheap and effective against a wide range of organisms, including Pneumocystis jiroveci pneumonia (PCP), which is an important cause of death and illness in the first year of life. It is safe with relatively few side effects. Diagnosis of HIV in children is complicated by the presence of maternal antibodies in early life. Providing prophylaxis based initially on maternal status is one possible solution. 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 children with HIV infection, and in infants of HIV-infected mothers.

Search methods

We searched the Cochrane HIV/AIDS registry, MEDLINE, the Cochrane Controlled Trials Register, LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and abstracts from AIDS and TB conferences (search date Feb 2005). We checked reference lists of 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 children (age less than 15 years) with HIV infection, or children less than 18 months with HIV infected mothers.

Data collection and analysis

Two reviewers independently assessed trial eligibility and quality. Where data were incomplete or unclear trial authors were contacted for further details.

Main results

One study was identified that fulfilled the inclusion criteria. It studied 534 children with HIV infection in Lusaka, Zambia. The study was conducted in an area of high bacterial resistance to cotrimoxazole (60-80%). A reduction in mortality of 33% was seen in the cotrimoxazole group as compared to placebo, relative risk 0.67 (95% CI 0.53 - 0.85). There was also a beneficial effect on hospitalisation, relative risk 0.77 (95% CI 0.62 - 0.96). There was no difference in adverse events between groups, and the beneficial effect was seen across all ages and CD4%.

Authors' conclusions

A single trial has shown a beneficial effect from the use of cotrimoxazole prophylaxis in HIV infected children in Zambia. It must be decided whether this can be extrapolated to other resource-poor settings.

Author(s)

Grimwade Kate, Swingler George H

Summary

The majority of children with HIV infection live in low-income countries without access to antiretroviral drugs. The prevention and early treatment of opportunistic infections are the mainstay of their medical management. Cotrimoxazole is cheap and effective against a wide range of organisms, including Pneumocystis jiroveci pneumonia (PCP), which is an important cause of death and illness in the first year of life. It is safe with relatively few side effects.

One study fulfilled the inclusion criteria for this review. This was a well-conducted trial of good methodological quality. It shows a significant reduction in mortality in children between the ages of 1 and 15 years, taking cotrimoxazole in comparison to placebo. Using cotrimoxazole in HIV-infected children waiting for antiretroviral treatment, or not yet requiring it, may increase survival and reduce the number of days spent in hospital.

Reviewer's Conclusions

Implications for practice

Antiretroviral treatment is becoming available in low-income countries but will take time to roll out and there will never be enough drugs for all those infected with HIV. Using cotrimoxazole in HIV-infected children waiting for antiretroviral treatment, or not yet requiring it, may increase survival and reduce the number of days spent in hospital.

Implications for research

Surveillance to evaluate the effects of widespread cotrimoxazole use on bacterial and malarial resistance will be essential to guide future treatment protocols. If it is felt that the findings of this single study cannot be automatically extrapolated to other areas, further work to look at the effect of prophylaxis will be required. It is unlikely following this trial that the use of placebo to investigate the effects of prophylaxis in children would be considered ethical.

As the provision of antiretroviral drugs for the definitive treatment of HIV infection is rolled out across low-income settings, research is needed to identify the appropriate use of cotrimoxazole in this setting, in particular looking at the safety of stopping prophylaxis once immunity has been restored on antiretroviral treatment.

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