***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: Objectives : To evaluate , over 12 weeks , the antiretroviral activity and safety of abacavir , used alone and in combination with zidovudine ( ZDV ) , as treatment for HIV-1-infected subjects who had limited or no antiretroviral treatment . Design : Seventy-nine HIV-1-infected subjects , with CD4 cell counts 200–500 × 106/l and < 12 weeks of previous treatment with ZDV were enrolled in a multicenter study . Subjects were r and omly assigned to one of four cohorts receiving abacavir monotherapy for the first 4 weeks ( 200 , 400 , or 600 mg every 8 h daily , or 300 mg every 12 h daily ) and , thereafter , combination therapy of abacavir with 600 mg ZDV or ZDV placebo , administered in a double-blind manner for an additional 8 weeks . Methods : Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4 + cell counts . Safety was assessed by monitoring clinical adverse events and laboratory abnormalities during the 12-week period and for 4 weeks post-treatment . Results : Treatment with abacavir , alone or in combination with ZDV , produced marked decreases in plasma HIV-1 RNA loads and increases in CD4 + cell counts in all groups . At week 4 , median plasma HIV-1 RNA loads decreased by 1.11–1.77 log10 copies/ml and median CD4 + cell counts increased by 63–111 × 106/l in all groups . At week 12 , median HIV-1 RNA loads decreased by 1.02–2.24 log10 copies/ml ( abacavir monotherapy ) and by 1.81–2.01 log10 copies/ml ( abacavir-ZDV ) ; median CD4 + cell counts increased by 79–195 × 106/l ( abacavir monotherapy ) and by 93–142 × 106/l ( abacavir-ZDV ) . At week 12 , the percentage of subjects who had plasma HIV-1 RNA levels below 400 and 40 copies/ml were 28 and 11 % , respectively ( abacavir monotherapy ) and 69 and 22 % , respectively ( abacavir-ZDV ) . Eight subjects ( 10 % ) discontinued the study prematurely because of adverse events ; nausea ( n = 4 ) and hypersensitivity ( n = 3 ) were the most common reasons for withdrawal . There were no deaths among the study subjects . Conclusions : In HIV-infected subjects who have received little or no prior antiretroviral therapy , treatment with abacavir alone or in combination with ZDV is well tolerated and result ed in sustained improvements in key immunologic and virologic efficacy parameters through 12 weeks Objectives . To evaluate the pharmacokinetic features , safety , and tolerance of abacavir , given alone and in combination with other nucleoside antiretroviral agents , in symptomatic human immunodeficiency virus (HIV)-infected children . Methods . HIV-infected children discontinued prior antiretroviral therapy  and were given abacavir orally , 4 mg/kg every 12 hours for 6 weeks , followed by 8 mg/kg every 12 hours for 6 weeks ( n = 39 ) ; or 8 mg/kg every 12 hours for 12 weeks ( n = 8) . Children then were r and omized to receive a second nucleoside antiretroviral agent ( zidovudine , stavudine , didanosine , or lamivudine ) , plus abacavir .  Pharmacokinetics , safety , tolerance , CD4 + lymphocyte counts , and plasma HIV RNA concentrations were evaluated . Results . At a dose of 8 mg/kg every 12 hours , area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily . One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy . Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent . Mean CD4+lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy . Conclusions . Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children . Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults Background Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors ( NRTIs ) for the treatment of HIV infections among children and adolescents . However , there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children . There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases . Methods We plan to do a systematic review to evaluate the antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children aged between 3 months and 18 years , compared with other NRTIs . We will search Scopus , Cochrane Central Register of Controlled Trials , MEDLINE , and Web of Science data bases for eligible studies regardless of language or publication status . We will check the reference lists of included studies , search relevant conference proceedings , email the authors of included studies and also look for unpublished and ongoing trials in prospect i ve clinical trial registries . Two authors will independently screen search outputs , select studies , extract data and assess the risk of bias in included studies . All disagreements will be resolved by discussion and consensus . Where data allow , we will conduct meta- analysis for similar types of participants , study design s , interventions , and outcome measures . If the results are statistically homogeneous , we will use the fixed-effect model ; otherwise , we will use the r and om-effects model and explore the reasons for heterogeneity using subgroup analyses . Heterogeneity will be assessed with the Chi-squared test and quantified with the I-squared statistic . Discussion The findings will be useful to policy makers and programme managers to inform treatment and management of HIV in children and adolescents and to point out research gaps for future research .Trial registration This review is registered with PROSPERO , registration number CRD42014009157 INTRODUCTION Treatment options for children with HIV-1 are limited . We aim ed to compare activity and safety of three dual-nucleoside analogue reverse-transcriptase inhibitor ( NRTI ) regimens with or without a protease inhibitor in previously untreated children with HIV-1 . METHODS In our multicentre trial , we r and omly assigned 36 children to zidovudine and lamivudine , 45 to zidovudine and abacavir , and 47 to lamivudine and abacavir . Children who were symptom-free ( n=55 ) were also r and omly assigned to receive nelfinavir or placebo .  Children with more advanced disease received open-label nelfinavir ( 73 ) . Primary endpoints were change in plasma HIV-1 RNA at 24 and 48 weeks for the NRTI comparison and occurrence of serious adverse events for both r and omised comparisons . Analyses were by intention to treat . FINDINGS Children had a median CD4 percentage of 22 % ( IQR 15 - 29 ) and a mean HIV-1 RNA concentration of 5.0 log copies/mL ( SD 0.8 ) . One child was lost to follow-up and one died of sepsis . At 48 weeks , in the zidovudine/lamivudine , zidovudine/abacavir , and lamivudine/abacavir groups , mean HIV-1 RNA had decreased by 1.71 , 2.19 , and 2.63 log copies/mL , respectively ( estimated in absence of nelfinavir ) ( p=0.02 after adjustment for baseline factors ) . One child had a hypersensitivity reaction to abacavir ; and three with possible reactions stopped abacavir . There were 24 serious adverse events -- six in the symptom-free children ( all on nelfinavir ) , but none were attributed to nelfinavir . INTERPRETATION Regimens containing abacavir were more effective than zidovudine/lamivudine . Such regimens could be combined with protease inhibitors and non-nucleoside reverse transcriptase inhibitors for safe and effective treatment of previously untreated children with HIV-1 Background : Twice-daily darunavir/ritonavir is indicated in treatment-experienced children ( ≥3 years ) . This study assessed once-daily administration in treatment-naïve adolescents . Methods : Phase 2 , 48-week , open-label , single-arm study evaluating pharmacokinetics , safety and efficacy of once-daily darunavir/ritonavir 800/100 mg in treatment-naïve , HIV-1–infected adolescents ( ≥12 to < 18 years , ≥40 kg ) with zidovudine/lamivudine or abacavir/lamivudine .  Results : Twelve patients ( 67 % female ; median 14.4 years ) were enrolled . After 24 and 48 weeks , respectively , 11 of 12 ( 92 % ) and 10 of 12 ( 83 % ) patients achieved viral load < 50 copies/mL ( intent-to-treat time-to-loss of virologic response ) ; all had ≥1 log10 drop in viral load versus baseline . Median CD4 + cell count increased by 175 and 221 cells/mm3 ( intent-to-treat-noncompleter = failure ) after 24 and 48 weeks , respectively . Eighty-three percent of patients were adherent to darunavir/ritonavir . One patient was never suppressed and 1 patient rebounded . No patients  developed darunavir resistance-associated mutations or lost phenotypic susceptibility to any commercially available protease inhibitor or any background nucleoside reverse transcriptase inhibitor . Eleven patients ( 92 % ) reported ≥1 adverse event ( AE ) , considered in 2 patients to be at least possibly related to darunavir ( gastrointestinal-related events and dizziness ) . Four patients had ≥1 serious AE . Three patients reported ≥1 grade 3/4 AE ; no serious or grade 3/4 AEs were considered darunavir related . No patients discontinued because of AEs . Conclusions : Over 48 weeks , once-daily darunavir/ritonavir 800/100 mg plus NRTIs was effective and well-tolerated for treatment of HIV-1–infected , antiretroviral-naïve adolescents ( ≥12 to < 18 years ) . These findings support use of once-daily darunavir/ritonavir 800/100 mg in this population BACKGROUND Few studies have investigated objective markers of lipodystrophy in African children . We compared body circumferences , skin-fold thickness ( SFT ) and lipids in  antiretroviral therapy (ART)-naive and stavudine (d4T)-exposed children with HIV-uninfected controls . METHODS In the CHAPAS-3 trial , HIV-infected children ( ART-naive or on d4 T for ≥2 years without clinical lipodystrophy ) were r and omized to d4 T , abacavir or zidovudine with lamivudine ( 3TC ) plus a non-nucleoside reverse transcriptase inhibitor . Mid-upper-arm circumference ( MUAC ) and calf circumference ( CC ) , SFT ( biceps , triceps , sub-scapular and supra-iliac ) and fasting lipids ( total cholesterol [ TC ] , low-density lipoprotein [ LDL ] , high-density lipoprotein [ HDL ] and triglycerides [ TRIG ] ) were measured at r and omization in all HIV-infected children , and in HIV-uninfected controls . Age- and sex-adjusted z-scores of MUAC , CC , SFT and the sum of SFT ( SSF ) using Dutch reference data were compared across groups using linear regression . RESULTS Of 496 children , 49 % were male , 299 ( median age 2.5 years [ IQR 1.5 - 4.0 ] ) were ART-naive , 109 ( median age 6 years [ IQR 5.5 - 7.0 ] ) were ART-experienced and 88 ( median age 2.2 years [ IQR 1.5 - 3.0 ] ) were control children . Overall , 100 % and 95 % of ART-experienced children had been on d4 T plus 3TC and nevirapine , respectively , for a median 3.5 years ( IQR 2.6 - 4.2 ) . Mean ( sd ) weight-for-age z-scores and MUAC z-scores were -1.51 ( 1.29 ) versus -0.90 ( 0.88 ) versus -0.33 ( 1.15 ) and -1.56 ( 1.25 ) versus -1.24 ( 0.97 ) versus -0. 
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The quality of evidence from RCTs was moderate for virologic suppression but low for death and adverse events , while that of cohort studies was low for all three these outcomes .
Conclusions Available evidence showed little or no difference between abacavir-containing regimen and other NRTIs regarding efficacy and safety when given to children and adolescents as a first-line antiretroviral therapy