***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND No trials of co-trimoxazole ( trimethoprim-sulfamethoxazole ) prophylaxis for HIV-infected adults or children have been done in areas with high levels of bacterial resistance to this antibiotic . We aim ed to assess the efficacy of daily co-trimoxazole in such an area . METHODS We did a double-blind r and omised placebo-controlled trial in children aged 1 - 14 years with clinical features of HIV infection in Zambia . Primary outcomes were mortality and adverse events possibly related to treatment . Analysis was by intention to treat . FINDINGS In October , 2003 , the data and safety monitoring committee recommended early stopping of the trial . 541 children had been r and omly assigned ; seven were subsequently identified as HIV negative and excluded . After median follow-up of 19 months , 74 ( 28 % ) children in the co-trimoxazole group and 112 ( 42 % ) in the placebo group had died ( hazard ratio [ HR ] 0.57 [ 95 % CI 0.43 - 0.77 ] , p=0.0002 ) . This benefit applied in children followed up beyond 12 months ( n=320 , HR 0.48 [ 0.27 - 0.84 ] , test for heterogeneity p=0.60 ) and across all ages ( test for heterogeneity p=0.82 ) and baseline CD4 counts ( test for heterogeneity p=0.36 ) . 16 ( 6 % ) children in the co-trimoxazole group had grade 3 or 4 adverse events compared with 18 ( 7 % ) in the placebo group . These events included rash ( one placebo ) , and a neutrophil count on one occasion less than 0.5x10(9)/L ( 16 [ 6 % ] co-trimoxazole vs seven [ 3 % ] placebo , p=0.06 ) . Pneumocystis carinii was identified by immunofluorescence in only one ( placebo ) of 73 nasopharyngeal aspirates from children with pneumonia . INTERPRETATION Our results suggest that children of all ages with clinical features of HIV infection should receive co-trimoxazole prophylaxis in re source -poor setting s , irrespective of local resistance to this drug Background Several frameworks have been constructed to analyse the factors which influence and shape the uptake of evidence into policy processes in re source poor setting s , yet empirical analyses of health policy making in these setting s are relatively rare . National policy making for cotrimoxazole ( trimethoprim-sulfamethoxazole ) preventive therapy in developing countries offers a pertinent case for the application of a policy analysis lens . The provision of cotrimoxazole as a prophylaxis is an inexpensive and highly efficacious preventative intervention in HIV infected individuals , reducing both morbidity and mortality among adults and children with HIV/AIDS , yet evidence suggests that it has not been quickly or evenly scaled-up in re source poor setting s. Methods Comparative analysis was conducted in Malawi , Ug and a and Zambia , using the case study approach . We applied the ‘ RAPID ’ framework developed by the Overseas Development Institute ( ODI ) , and conducted a total of 47 in-depth interviews  across the three countries to examine the influence of context ( including the influence of donor agencies ) , evidence ( both local and international ) , and the links between research er , policy makers and those seeking to influence the policy process . Results Each area of analysis was found to have an influence on the creation of national policy on cotrimoxazole preventive therapy ( CPT ) in all three countries . In relation to context , the following were found to be influential : government structures and their focus , donor interest and involvement , healthcare infrastructure and other uses of cotrimoxazole and related drugs in the country . In terms of the nature of the evidence , we found that how policy makers perceived the strength of evidence behind international recommendations was crucial ( if evidence was considered weak then the recommendations were rejected ) . Further , local operational research results seem to have been taken up more quickly , while r and omised controlled trials ( the gold st and ard of clinical research ) was not necessarily translated into policy so swiftly . Finally the links between different research and policy actors were of critical importance , with overlaps between research er and policy maker networks crucial to facilitate knowledge transfer . Within these networks , in each country the policy development process relied on a powerful policy entrepreneur who helped get cotrimoxazole preventive therapy onto the policy agenda . Conclusions This analysis underscores the importance of considering national level variables in the explanation of the uptake of evidence into national policy setting s , and recognising how local policy makers interpret international evidence . Local priorities , the ways in which evidence was interpreted , and the nature of the links between policy makers and research ers could either drive or stall the policy process . Developing the underst and ing of these processes enables the explanation of the use ( or non-use ) of evidence in policy making , and potentially may help to shape future strategies to bridge the research -policy gaps and ultimately improve the uptake of evidence in decision making Background Clinical evolution of HIV-infected children who have not yet initiated antiretroviral treatment ( ART ) is poorly understood in Africa . We describe severe morbidity and mortality of untreated HIV-infected children . Methods All HIV-infected children enrolled from 2004 - 2009 in a prospect i ve HIV programme in two health facilities in Abidjan , Côte d'Ivoire , were eligible from their time of inclusion . Risks of severe morbidity ( the first clinical event leading to death or hospitalisation ) and mortality were documented retrospectively and estimated using cumulative incidence functions . Associations with baseline characteristics were assessed by competing risk regression models between outcomes and antiretroviral initiation . Results 405 children were included at a median age of 4.5 years ; at baseline , 66.9 % were receiving cotrimoxazole prophylaxis , and 27.7 % met the 2006 WHO criteria for immunodeficiency by age . The risk of developing a severe morbid event was 14 % ( 95%CI : 10.7 - 17.8 ) at 18 months ; this risk was lower in children previously exposed to any prevention of mother-to-child-transmission ( PMTCT ) intervention ( adjusted subdistribution hazard ratio [ sHR ] : 0.16 , 95 % CI : 0.04 - 0.71 ) versus those without known exposure . Cumulative mortality reached 5.5 % ( 95%CI : 3.5 - 8.1 ) at 18 months . Mortality was associated with immunodeficiency ( sHR : 6.02 , 95 % CI : 1.28 - 28.42 ) . Conclusions Having benefited from early access to care minimizes the severe morbidity risk for children who acquire HIV . Despite the receipt of cotrimoxazole prophylaxis , the risk of severe morbidity and mortality remains high in untreated HIV-infected children . Such evidence adds arguments to promote earlier access to ART in HIV-infected children in Africa and improve care interventions in a context where treatment is still not available to all The purpose of this prospect i ve cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members . A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed . Study participants were living in households where HIV-infected persons were either taking ( exposed ) or not taking ( unexposed ) cotrimoxazole prophylaxis .  From all malaria episodes diagnosed , 50 % of the specimens were r and omly selected and tested for the presence of five key mutations known to mediate resistance to SP ( dihydrofolate reductase [ dhfr ] Asn-108 , Ile-51 , and Arg-59 , and dihydropteroate synthase [ dhps ] Gly-437 and Glu-540 ) . Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households , with similar proportions containing the dhfr triple mutant ( 37 % versus 45 % ; P = 0.18 ) , the dhps double mutant ( 64 % versus 62 % ; P = 0.81 ) , and the dhfr/dhps quintuple mutant ( 30 % versus 32 % ; P = 0.74 ) . The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria ( incidence rate ratio [ IRR ] = 0.64 , 95 % confidence interval [ CI ] = 0.50 - 0.83 , P = 0.001 ) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant ( IRR = 0.61 , 95 % CI = 0.41 - 0.91 , P = 0.014 ) . Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members , and was associated with a lower overall incidence of SP-resistant malaria among household members 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 r and omized , noninferiority trial of stopping versus continuing daily open-label co-trimoxazole in children and adolescents in Ug and a 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 . Co primary end points were hospitalization or death and adverse events of grade 3 or 4 . RESULTS A total of 758 participants were r and omly 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 , IS RCT N24791884 . ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children ( uninfected children born to HIV infected mothers ) in Africa . Design Non-blinded r and omised control trial Setting Tororo district , rural Ug and a , an area of high malaria transmission intensity Participants 203 breastfeeding HIV exposed infants enrolled between 6 weeks and 9 months of age Intervention Co-trimoxazole prophylaxis from enrolment until cessation of breast feeding and confirmation of negative HIV status . All children who remained HIV uninfected ( n=185 ) were then r and omised to stop co-trimoxazole prophylaxis immediately or continue co-trimoxazole until 2 years old . Main outcome measure Incidence 
    Output:
    
In meta-regression analyses , there was some evidence that the efficacy of CPT  declined with increasing levels of resistance .
CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children