Effect sizes will be reported alongside 95% confidence intervals. Meta-analysis will be done using the fixed-effect model when the Chi-squared test yields em P /em ? ?0.1 or when the I-squared value is below 50%; otherwise, the random-effects model will be used. 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of included studies, search relevant conference proceedings, email the authors of included studies and also look for unpublished and ongoing trials in prospective clinical trial registries.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 designs, interventions, and outcome measures. If the results are statistically homogeneous, we will use the fixed-effect model; otherwise, we will use the random-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. lamivudine, abacavir, zidovudine, stavudine, efavirenz, emtricitabine, lopinavir/ritonavir, nevirapine, tenofovir, World Health Organization. The WHO guidelines suggest that stavudine, a NRTI, be replaced by abacavir because of toxicity concerns. However, abacavir has adverse effect concerns of its own [4]. Abacavir is associated with a systemic illness known as that can result in death if the drug is not discontinued in affected patients. This hypersensitivity may present with fever, maculopapular rash and other constitutional symptoms such as fatigue, malaise and myalgia. Gastrointestinal adverse effects such as vomiting, diarrhoea and abdominal pain may also occur. Occasionally, there are also some prominent respiratory symptoms, such as tachypnea and cough [5,6]. Hypersensitivity reactions due to abacavir have been reported in both paediatric and adult populations with the incidence in randomised controlled trials ranging from 0% to 14% [6]. HIV-infected individuals of African descent seems to have reduced risk of abacavir hypersensitivity [7], and the wide variation in reported adverse event incidence with abacavir use makes it necessary to do a systematic review, especially in children. In addition, some cohort studies in South (±)-Epibatidine Africa have shown poor virological responses to abacavir-based regimens when compared to stavudine in children. These studies queried the clinical effectiveness of abacavir when compared to the other NRTIs as well as the justification for making it a first-line drug in the treatment of HIV in children [8,9]. A further investigation on the drug is thus needed. Some research studies suggested that abacavir increases the risk of cardiovascular events, especially myocardial infarction [10,11]. However, meta-analyses of randomised controlled trials in adults have not supported the postulation that abacavir-containing antiretroviral regimens carry a greater risk of cardiovascular events relative to abacavir-sparing regimens [12,13]. Similarly, various studies evaluating changes in inflammatory and coagulopathic biomarkers upon commencement of abacavir-containing regimens have produced conflicting findings [14,15]. These randomised controlled trials were carried out mainly on adults due to the belief that children have lower incidence of some of these important adverse effects of abacavir [16]. A meta-analysis of HIV-infected adults switching to abacavir-containing regimens shows rather weak evidence of lower incidence of adverse events, with higher incidence of virological failure in the NRTI groups when compared to the controls [17]. Despite concerns that the confidence in the currently available evidence on the antiviral efficacy of abacavir might be low, coupled with serious adverse events such as hypersensitivity reactions and a potential predisposition to developing cardiovascular diseases, the WHO has recommended abacavir as one of the preferred NRTI backbones in the paediatric population [4]. However, we are not aware of any systematic review of the safety of abacavir-containing regimens in HIV-infected children. Objective The primary objective is to assess the antiviral efficacy of abacavir-containing combination antiretroviral regimens in comparison with combination antiretroviral regimens containing other NRTIs as first-line therapy for HIV-infected children.Myocardial infarction and other cardiovascular events Search methods for identification of studies With the support of a librarian at the University of Stellenbosch’s Faculty of Medicine and Health Sciences, we will do an exhaustive search to identify all the relevant studies regardless of language or publication status. em Databases /em We will search the following electronic databases: MEDLINE via PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ISI Web of Science (Science Citation Index). 18?years, compared with other NRTIs. We will search Scopus, Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science databases 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 prospective clinical trial registries. Two authors will independently screen search outputs, select studies, extract data and assess the threat of bias in included research. All disagreements will end up being resolved by (±)-Epibatidine debate and consensus. Where data enable, we will carry out meta-analysis for very similar types of individuals, study styles, interventions, and final result methods. If the email address details are statistically homogeneous, we use the fixed-effect model; usually, we use the random-effects model and explore the reason why for heterogeneity using subgroup analyses. Heterogeneity will end up being assessed using the Chi-squared ensure that you quantified using the I-squared statistic. Debate The results will end up being useful to plan makers and program managers to see treatment and administration of HIV in kids and adolescents also to point out analysis gaps for potential research. Trial enrollment This review is normally signed up with PROSPERO, enrollment amount CRD42014009157. lamivudine, abacavir, zidovudine, stavudine, efavirenz, emtricitabine, lopinavir/ritonavir, nevirapine, tenofovir, Globe Health Company. The WHO suggestions claim that stavudine, a NRTI, end up being changed by abacavir due to toxicity concerns. Nevertheless, abacavir has undesirable effect problems of its [4]. Abacavir is normally connected with a systemic disease known as that may result in loss of life if the medication isn’t discontinued in affected sufferers. This hypersensitivity may present with fever, maculopapular rash and various other constitutional symptoms such as for example exhaustion, malaise and myalgia. Gastrointestinal undesireable effects such as throwing up, diarrhoea and stomach pain could also take place. Occasionally, there’s also some prominent respiratory symptoms, such as for example tachypnea and coughing [5,6]. Hypersensitivity reactions because of abacavir have already been reported in both paediatric and adult populations using the occurrence in randomised managed studies which range from 0% to 14% [6]. HIV-infected people of African descent appears to have decreased threat of abacavir hypersensitivity [7], as well as the wide deviation in reported adverse event occurrence with abacavir make use of makes it essential to do a organized review, specifically in children. Furthermore, some cohort research in South Africa show (±)-Epibatidine poor virological replies to abacavir-based regimens in comparison with stavudine in kids. These research queried the scientific efficiency of abacavir in comparison with the various other NRTIs aswell as the justification to make it a first-line medication in the treating HIV in kids [8,9]. An additional investigation over the medication is thus required. Some clinical tests recommended that abacavir escalates the threat of cardiovascular occasions, specifically myocardial infarction [10,11]. Nevertheless, meta-analyses of randomised managed studies in adults never have backed the postulation that abacavir-containing antiretroviral regimens bring a greater threat of cardiovascular occasions in accordance with abacavir-sparing regimens [12,13]. Likewise, various research evaluating adjustments in inflammatory and coagulopathic biomarkers upon commencement of abacavir-containing regimens possess produced conflicting results [14,15]. These randomised managed studies were completed Rabbit Polyclonal to OR9Q1 generally on adults because of the perception that children have got lower occurrence of a few of these essential undesireable effects of abacavir [16]. A meta-analysis of HIV-infected adults switching to abacavir-containing regimens displays rather weak proof lower occurrence of adverse occasions, with higher occurrence of virological failing in the NRTI groupings (±)-Epibatidine in comparison with the handles [17]. Despite problems that the self-confidence in the available evidence over the antiviral efficiency of abacavir may be low, in conjunction with critical adverse occasions such as for example hypersensitivity reactions and a potential predisposition to developing cardiovascular illnesses, the That has suggested abacavir among the desired NRTI backbones in the paediatric people [4]. Nevertheless, we have no idea of any organized overview of the basic safety of abacavir-containing regimens in HIV-infected kids. Objective The principal objective is normally to measure the antiviral efficiency of abacavir-containing mixture antiretroviral regimens in comparison to mixture antiretroviral regimens filled with various other NRTIs as first-line therapy for HIV-infected kids and adolescents. The secondary objective is to measure the safety of abacavir-containing combination antiretroviral regimens in HIV-infected adolescents and children. Strategies This review process has been released in the PROSPERO International Potential Register of organized testimonials (http://www.crd.york.ac.uk/PROSPERO), enrollment amount CRD42014009157 [18]. The PROSPERO data source provides a extensive listing of organized reviews registered in the beginning to greatly help prevent unintended duplication and enables comparison of released review methods using what was designed in the process. Criteria for taking into consideration research because of this review em Types of research /em Experimental (randomised managed studies and non-randomised managed studies) and potential observational research with control groupings will qualify for inclusion within this organized review. Non-randomised managed studies refer to research that.