***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: Summary Background WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years . No paediatric trials have compared nucleoside reverse-transcriptase inhibitors ( NRTIs ) in first-line antiretroviral therapy ( ART ) in Africa , where most HIV-infected children live . We aim ed to compare stavudine , zidovudine , or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz . Methods In this open-label , parallel-group , r and omised trial ( CHAPAS-3 ) , we enrolled children from one centre in Zambia and three in Ug and a who were previously untreated ( ART naive ) or on stavudine for more than 2 years with viral load less than 50 copies per mL ( ART experienced ) . Computer-generated r and omisation tables were incorporated securely within the data base . The primary endpoint was grade 2–4 clinical or grade 3/4 laboratory adverse events . Analysis was intention to treat . This trial is registered with the IS RCT N Registry number , 69078957 . Findings Between Nov 8 , 2010 , and Dec 28 , 2011 , 480 children were r and omised : 156 to stavudine , 159 to zidovudine , and 165 to abacavir . After two were excluded due to r and omisation error , 156 children were analysed in the stavudine group , 158 in the zidovudine group , and 164 in the abacavir group , and followed for median 2·3 years ( 5 % lost to follow-up ) . 365 ( 76 % ) were ART naive ( median age 2·6 years vs 6·2 years in ART experienced ) . 917 grade 2–4 clinical or grade 3/4 laboratory adverse events ( 835 clinical [ 634 grade 2 ] ; 40 laboratory ) occurred in 104 ( 67 % ) children on stavudine , 103 ( 65 % ) on zidovudine , and 105 ( 64 % ) , on abacavir ( p=0·63 ; zidovudine vs stavudine : hazard ratio [ HR ] 0·99 [ 95 % CI 0·75–1·29 ] ; abacavir vs stavudine : HR 0·88 [ 0·67–1·15 ] ) . At 48 weeks , 98 ( 85 % ) , 81 ( 80 % ) and 95 ( 81 % ) ART-naive children in the stavudine , zidovudine , and abacavir groups , respectively , had viral load less than 400 copies per mL ( p=0·58 ) ; most ART-experienced children maintained suppression ( p=1·00 ) . Interpretation All NRTIs had low toxicity and good clinical , immunological , and virological responses . Clinical and sub clinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs . Absence of hypersensitivity reactions , superior resistance profile and once-daily dosing favours abacavir for African children , supporting WHO 2013 guidelines . Funding European Developing Countries Clinical Trials Partnership Mitochondrial damage is implicated in highly active antiretroviral therapy ( HAART ) toxicity . HIV infection also causes mitochondrial toxicity ( MT ) . Differentiating between the two is critical for HIV management . Our objective was to test the utility of the Mitochondrial Disease Criteria ( MDC ) and the Enquête Périnatale Française ( EPF ) to screen for possible HAART related MT in HIV-infected children in Ghana . The EPF and MDC are compilations of clinical symptoms , or criteria , of MT : a ( + ) score indicates possible MT . We applied these criteria retrospectively to 403 charts of HIV-infected children . Of those studied , 331/403 received HAART . Comparing HAART exposed and HAART naïve children , the difference in EPF score , but not MDC , approached significance ( P = 0.1 ) . Young age at HIV diagnosis or at HAART initiation was associated with ( + ) EPF ( P ≤ 0.01 ) . Adherence to HAART trended toward an association with ( + ) EPF ( P = 0.09 ) . Exposure to nevirapine , abacavir , or didanosine increased risk of ( + ) EPF ( OR = 3.55 ( CI = 1.99–6.33 ) , 4.76 ( 2.39–9.43 ) , 4.93 ( 1.29–18.87 ) ) . Neither EPF nor MDC identified a significant difference between HAART exposed or naïve children regarding possible MT . However , as indicators of HAART exposure are associated with ( + ) EPF , it may be a c and i date for prospect i ve study of possible HAART related MT in re source -poor setting Background : Pharmacokinetics , safety and antiviral activity of twice-daily fosamprenavir with or without ritonavir were evaluated in 2- to 18-year-old protease inhibitor – naïve and -experienced HIV-1–infected children . Methods : Serial pharmacokinetic sample s were collected at week 2 and predose sample s every 4–12 weeks . Safety and plasma HIV-1 RNA were monitored every 4–12 weeks . Results : Twenty protease inhibitor – naïve 2- to < 6-year-old subjects received antiretroviral treatment including unboosted fosamprenavir twice-daily , whereas 89 protease inhibitor – naïve and -experienced 2- to 18-year-old subjects  received fosamprenavir/ritonavir-containing therapy twice-daily . Median fosamprenavir exposure was 891 days ( range 15–1805 days ) , with 88 % exposed > 48 weeks . Twice-daily doses of fosamprenavir/ritonavir 23/3 mg/kg in 2- to < 6-year olds , 18/3 mg/kg in ≥6-year olds and 700/100 mg in adolescents achieved plasma amprenavir exposures comparable with or higher than 700/100 mg twice-daily in adults while fosamprenavir 30 mg/kg twice-daily in 2- to < 6-year olds led to exposures higher than 1400 mg twice-daily in adults . The proportion of subjects with HIV-1 RNA < 400 copies/mL at week 48 was 60 % for fosamprenavir and 53–74 % for fosamprenavir/ritonavir ( intent-to-treat [ exposed ] , snapshot analysis ) . Median increases in absolute and relative ( percentage ) CD4 counts from baseline to week 48 occurred in both the fosamprenavir ( 340 cells/mm3 ; 8 % ) and fosamprenavir/ritonavir group ( 190 cells/mm3 ; 8 % ) . The most common adverse events were vomiting , cough , and diarrhea ;  18 subjects  experienced serious adverse events , including 9 with suspected abacavir hypersensitivity . Conclusions : Fosamprenavir regimens administered to HIV-1–infected children aged 2–18 years were generally well-tolerated and provided sustained antiviral activity over 48 weeks , with plasma amprenavir exposures comparable with or higher than adults An extensive and growing number of review s of the published literature demonstrate that health research publications have frequent deficiencies . Of particular concern are poor reports of r and omised trials , which make it difficult or impossible for readers to assess how the research was conducted , to evaluate the reliability of the findings , or to place them in the context of existing research evidence . As a result , published reports of trials often can not be used by clinicians to inform patient care or to inform public health policy , and the data can not be included in systematic review s. Reporting guidelines are design ed to identify the key information that research ers should include in a report of their research . We describe the history of reporting guidelines for r and omised trials culminating in the CONSORT Statement in 1996 . We detail the subsequent development and extension of CONSORT and consider related initiatives aim ed at improving the reliability of the medical research literature BACKGROUND No data on once-daily dosing of nucleoside analogues in African children currently exist . We compared the pharmacokinetics ( PK ) of once- versus twice-daily lamivudine and abacavir treatment using the World Health Organization recommended weight b and dosing of scored adult tablets . METHODS HIV type-1 (HIV-1)-infected Ug and an children aged 3 - 12 years receiving antiretroviral therapy that included lamivudine and abacavir twice daily ( total 150 + 300 mg , 225 + 450 mg and 225/300 + 600 mg daily for 12-<20 , 20-<25 and ≥25 kg , respectively ) were enrolled in a crossover study . Plasma PK sampling ( at 0 , 1 , 2 , 4 , 6 , 8 and 12 h after observed morning intake ) was performed for the twice-daily regimen at steady-state . Children were then switched to once-daily treatment with PK sampling repeated 4 weeks later ( with an additional 24 h sample ) . Acceptability question naires were completed at both time points . Daily area under the curve ( AUC(0 - 24 ) ) and maximum concentrations ( C(max ) ) were compared by geometric mean ratios ( GMRs ) . RESULTS A total of 41 HIV-1-infected children ( median age of 7 years ) and n=23 , n=14 and n=4 in 12-<20 , 20-<25 and ≥25 kg weight b and s , respectively , were enrolled . Mean AUC(0 - 24 ) was 13.0 and 12.0 mg•h/l for once- and twice-daily lamivudine ( GMR 1.09 , 90 % confidence intervals [ CI ] 0.98 - 1.20 ) and 15.3 and 15.6 mg•h/l for once- and twice-daily abacavir ( GMR 0.98 , 90 % CI 0.89 - 1.08 ) , respectively , with no difference in 3 - 6 versus 7 - 12 year olds . C(max ) was 76 % ( lamivudine ) and 64 % ( abacavir ) higher on once-daily regimens . For both children and caregivers , once-daily dosing of lamivudine plus abacavir was highly acceptable and strongly preferred over twice-daily . CONCLUSIONS In children aged 3 - 12 years  , AUC(0 - 24 ) of lamivudine and abacavir were bioequivalent on once- and twice-daily regimens . Once-daily dosing of abacavir and lamivudine could provide an alternative dosing strategy for HIV-1-infected children , with high acceptability and strong preference suggesting the potential for improved adherence This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Objective : To describe the long-term efficacy over 5 years of regimens including combinations of abacavir , lamivudine and /or zidovudine in previously untreated children in the PENTA 5 trial . Design : PENTA 5 was a 48-week r and omised controlled trial comparing three dual nucleoside reverse transcriptase inhibitor ( NRTI ) combinations as part of first triple antiretroviral therapy ( ART ) . Methods : 128 ART-naïve children were r and omised to zidovudine\lamivudine ( n = 36 ) , zidovudine\abacavir ( 45 ) or lamivudine\abacavir ( 47 ) . Asymptomatic children ( n = 55 ) were also r and omised to nelfinavir or placebo ; all other children received open-label nelfinavir . Analyses are intent-to-treat and adjusted for minor baseline imbalances and receipt of nelfinavir/placebo . Results : Median follow-up was 5.8 years . By 5 years , 17 ( 47 % ) , 28 ( 
    Output:
    
INTERPRETATION Abacavir-related toxicity occurs early after ART initiation and is manageable .
Abacavir can be safely used for first-line or second-line antiretroviral regimens in children and adolescents , especially in sub-Saharan Africa were HLA B5701 genotype is rare .