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A randomized controlled trial of intermittent compared with daily cotrimoxazole preventive therapy in HIV-infected children

Zar, Heather Ja; Workman, Lesleya; le Roux, Stanzi Ma; Jennings, Teresaa; Jele, Nomawethua; Schaaf, Hendrick Simonb; Barclay-Loggie, Anna; Mulligan, Chrisa; le Roux, David Ma; Lombard, Carl Jc; Cotton, Mark Fbthe INH study team

doi: 10.1097/QAD.0b013e32833d4533
Clinical Science

Objective: Cotrimoxazole preventive therapy (CPT) reduces morbidity and mortality in HIV-infected children. The WHO recommends prolonged daily CPT for HIV-infected infants and children. In adults, intermittent CPT has been associated with less adverse events than daily, with increased tolerability and equal efficacy. We investigated the efficacy and tolerability of intermittent CPT compared with daily CPT in HIV-infected children over a 5-year period.

Design: A prospective randomized controlled study.

Methods: HIV-infected children aged at least 8 weeks were randomized to thrice weekly or daily CPT. Outcome measures were mortality, bacterial infections, hospitalizations and adverse events.

Results: Three hundred and twenty-four children (median age 23 months) were followed for 672 child-years; 165 (51%) were randomized to intermittent CPT. Most children (287, 89%) were Centers for Disease Control and Prevention clinical category B or C; 207 (64%) received HAART during the study. Mortality (53 deaths, 16%) was similar in the intermittent CPT compared with the daily CPT group {24 (14%) vs. 29 (18%), hazard ratio 0.75 [95% confidence interval (CI) 0.44–1.29]}. The predominant causes of death in both groups were sepsis (17, 32%), pneumonia (13, 25%) or diarrhoea (8, 15%). Intermittent CPT was associated with more bacteraemias [incidence rate ratio 2.36 (95% CI 1.21–4.86)]. Children receiving intermittent CPT also spent more days in hospital [incidence rate ratio 1.15 (95% CI 1.04–1.28)]. The rate of serious adverse events was similar between groups [incidence rate ratio 1.07 (95% CI 0.58–2.02)].

Conclusion: Intermittent CPT was associated with more invasive bacterial disease than daily CPT, but survival was similar. Both regimens were well tolerated. On balance, daily CPT remains preferable to intermittent therapy for HIV-infected children.

aDepartment of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa

bDepartment of Paediatrics, Tygerberg Children's Hospital, Stellenbosch University, Stellenbosch, South Africa

cBiostatistics Unit, Medical Research Council, Cape Town, South Africa.

Received 26 March, 2010

Revised 7 June, 2010

Accepted 16 June, 2010

Correspondence to Professor Heather Zar, 5th floor ICH Building, Klipfontein Road, Rondebosch, Cape Town 7700, South Africa. Tel: +27 21 658 5318; fax: +27 21 689 1287; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.