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. 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.
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. 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-infectedpatients 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.
Authors: Jonathan Grant Peter; Rannakoe Lehloenya; Sipho Dlamini; Kimberly Risma; Katie D White; Katherine C Konvinse; Elizabeth J Phillips Journal: J Allergy Clin Immunol Pract Date: 2017 May - Jun