This review examines strategies to enable the continued use of the antibiotic cotrimoxazole in patients with HIV/AIDS to treat or prevent opportunistic infections in patients who previously experienced hypersensitivity to this drug.

Opportunistic infections are a threat to the lives and health of people living with HIV. Cotrimoxazole, an antibiotic also known as trimethoprim-sulfamethoxazole, is used in the treatment and prevention of several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole can cause more drug-related side effects than in the general population. However, there are not many effective alternatives for this drug, which is also by far the cheapest option available. When a patient with HIV experiences a side effect related to cotrimoxazole, often the drug is continued (treating-through) or reintroduced at a later date, either using increasingly larger doses (desensitization), or immediately starting at the full dose (rechallenge). This systematic review is the first to examine the differences in how patients are able to tolerate these strategies.

Three trials examining the use of cotrimoxazole in preventing opportunistic infections were included in the review. When compared to rechallenge, desensitization appeared to result in fewer treatment stoppages and side effects in HIV-infected adult patients who had a previous mild or moderate reaction to cotrimoxazole. However, more data are needed for these results to be conclusive. It is important to note that reintroduction of cotrimoxazole was usually successful using either desensitization or rechallenge, with 44.4% to 79.4% of patients still on cotrimoxazole after six months in the three studies. Furthermore, in the studies reviewed, no strategy resulted in severe hypersensitivity reactions. Severe limitations of this review included the absence of data in paediatric populations and the minimal data from resource-poor populations.

Authors' conclusions: 

In the small trials included in this review, when compared to cotrimoxazole rechallenge for prophylaxis of opportunistic infections, cotrimoxazole desensitization resulted in fewer treatment discontinuations and overall adverse reactions in HIV-infected patients with a previous history of mild or moderate hypersensitivity to cotrimoxazole. Paediatric data and trials in resource-poor settings are urgently required. Further randomised controlled trials are also needed for the treatment of opportunistic infections, treating-through, adjunctive medications, and different desensitization-dosing schedules.

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Background: 

Opportunistic infections continue to cause a significant amount of morbidity and mortality worldwide in patients infected with HIV. Trimethoprim-sulfamethoxazole (cotrimoxazole) is used in the treatment and prophylaxis of several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole use can cause a higher rate of adverse drug reactions than in the general population. Given the cost-effectiveness of cotrimoxazole, the management of these adverse reactions has included continuing the drug (treating-through) and reintroducing the drug at a later date, either using dose-escalation (desensitization), or rechallenge at full dose. This systematic review is the first to examine the differences in patient outcomes between these strategies.

Objectives: 

To compare the rate of discontinuation of cotrimoxazole and adverse reactions among the three strategies of treating-through, desensitization, and rechallenge in patients living with HIV who previously had an adverse reaction to cotrimoxazole.

Search strategy: 

We searched MEDLINE, EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, The National Institutes of Health Clinical Trials Registry, and CenterWatch (search date May 2006).

Selection criteria: 

Randomised trials comparing treating-through, rechallenge, or desensitization of cotrimoxazole treatment or prophylaxis in adults (age 18 years or over) and/or children (age 17 years or under).

Data collection and analysis: 

Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, a third reviewer resolved conflicts and/or trial authors were contacted for further details.

Main results: 

Three trials that examined cotrimoxazole prophylaxis and involving 268 adults were included. Meta-analysis of these studies found a beneficial effect of using a desensitization protocol over a rechallenge protocol at six months of follow-up for preventing discontinuation of cotrimoxazole (number needed to treat (NNT) 7.14, 95% confidence interval (CI) 4.0-33.0), and for lower incidence of overall hypersensitivity (NNT 4.55, 95% CI 3.03-9.09). No severe hypersensitivity reactions occurred for either protocol in the three studies.

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