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A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa.
Bwakura-Dangarembizi, Mutsawashe; Kendall, Lindsay; Bakeera-Kitaka, Sabrina; Nahirya-Ntege, Patricia; Keishanyu, Rosette; Nathoo, Kusum; Spyer, Moira J; Kekitiinwa, Adeodata; Lutaakome, Joseph; Mhute, Tawanda; Kasirye, Philip; Munderi, Paula; Musiime, Victor; Gibb, Diana M; Walker, A Sarah; Prendergast, Andrew J.
Affiliation
  • Bwakura-Dangarembizi M; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Kendall L; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Bakeera-Kitaka S; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Nahirya-Ntege P; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Keishanyu R; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Nathoo K; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Spyer MJ; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Kekitiinwa A; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Lutaakome J; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Mhute T; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Kasirye P; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Munderi P; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Musiime V; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Gibb DM; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Walker AS; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
  • Prendergast AJ; University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; an
N Engl J Med ; 370(1): 41-53, 2014 Jan 02.
Article in En | MEDLINE | ID: mdl-24382064
ABSTRACT

BACKGROUND:

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole.

METHODS:

We conducted a randomized, noninferiority trial of stopping versus continuing daily open-label co-trimoxazole in children and adolescents in Uganda and Zimbabwe. Eligible participants were older than 3 years of age, had been receiving ART for more than 96 weeks, were using insecticide-treated bed nets (in malaria-endemic areas), and had not had Pneumocystis jirovecii pneumonia. Coprimary end points were hospitalization or death and adverse events of grade 3 or 4.

RESULTS:

A total of 758 participants were randomly assigned to stop or continue co-trimoxazole (382 and 376 participants, respectively), after receiving ART for a median of 2.1 years (interquartile range, 1.8 to 2.3). The median age was 7.9 years (interquartile range, 4.6 to 11.1), and the median CD4 T-cell percentage was 33% (interquartile range, 26 to 39). Participants who stopped co-trimoxazole had higher rates of hospitalization or death than those who continued (72 participants [19%] vs. 48 [13%]; hazard ratio, 1.64; 95% confidence interval [CI], 1.14 to 2.37; P = 0.007; noninferiority not shown). There was no evidence of variation across ages (P=0.93 for interaction). A total of 2 participants in the prophylaxis-stopped group (1%) died, as did 3 in the prophylaxis-continued group (1%). Most hospitalizations in the prophylaxis-stopped group were for malaria (49 events, vs. 21 in the prophylaxis-continued group) or infections other than malaria (53 vs. 25), particularly pneumonia, sepsis, and meningitis. Rates of adverse events of grade 3 or 4 were similar in the two groups (hazard ratio, 1.20; 95% CI, 0.83 to 1.72; P=0.33), but more grade 4 adverse events occurred in the prophylaxis-stopped group (hazard ratio, 2.04; 95% CI, 0.99 to 4.22; P=0.05), with anemia accounting for the largest number of events (12, vs. 2 with continued prophylaxis).

CONCLUSIONS:

Continuing co-trimoxazole prophylaxis after 96 weeks of ART was beneficial, as compared with stopping prophylaxis, with fewer hospitalizations for both malaria and infection not related to malaria. (Funded by the United Kingdom Medical Research Council and others; ARROW Current Controlled Trials number, ISRCTN24791884.).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / Trimethoprim, Sulfamethoxazole Drug Combination / Anti-Retroviral Agents / Malaria / Anti-Infective Agents Type of study: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Country/Region as subject: Africa Language: En Journal: N Engl J Med Year: 2014 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / Trimethoprim, Sulfamethoxazole Drug Combination / Anti-Retroviral Agents / Malaria / Anti-Infective Agents Type of study: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Country/Region as subject: Africa Language: En Journal: N Engl J Med Year: 2014 Document type: Article