Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection and AIDS

Shey, Muki; Kongnyuy, Eugene J; Alobwede, Samuel Muabe; Wiysonge, Charles Shey

doi:10.1002/14651858.cd005481.pub3

Cited by 14 publications

(11 citation statements)

References 43 publications

(38 reference statements)

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“…Based on a search strategy published by Shey et al [ 24 ], we used both text words and medical subject heading (MeSH) terms, for example abacavir, antiretroviral, HIV, acquired immunodeficiency syndrome , child , paediatric , adolescent and randomized controlled trial to form the basis of the search strings. We also used these terms in different combinations and with different spellings, and adapted them as appropriate for each database.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis

et al. 2015

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BackgroundAbacavir 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 diseasesMethodsWe searched four electronic databases, four conference proceedings and two clinical trial registries in August 2014, without language restrictions. Experimental and observational studies with control groups that examined the efficacy and safety of abacavir-containing regimens in comparison with other NRTIs as first-line treatment for HIV-infected children and adolescents aged between one month and eighteen years were eligible. Two authors independently screened search results, extracted data and assessed the risk of bias of included studies using a pre-specified, standardised data extraction form and validated risk of bias tools. We also assessed the quality of evidence per outcome with the GRADE tool.ResultsWe included two randomised controlled trials (RCTs) and two analytical cohort studies with a total of 10,595 participants. Among the RCTs we detected no difference in virologic suppression after a mean duration of 48 weeks between abacavir- and stavudine-containing regimens (2 trials; n = 326: RR 1.28; 95 % CI 0.67–2.42) with significant heterogeneity (P = 0.02; I2 = 81 %). We also found no significant differences between the two groups for adverse events and death. After five years of follow-up, virologic suppression improved with abacavir (1 trial; n = 69: RR 1.96; 95 % CI 1.11–3.44). For cohort studies, we detected that the virologic suppression activity of abacavir was less effective than stavudine in both the lopinavir/ritonavir (1 study, n = 2165: RR 0.79, 95 % CI 0.67–0.92) and efavirenz sub-groups (1 study, n = 3204: RR 0.79, 95 % CI 0.67–0.92) respectively. 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.ConclusionsAvailable 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1183-6) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis

et al. 2015

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“…There are however systematic reviews on abacavir-containing combination antiretroviral regimens in adults [12,13,16,19]. The study team plans to address this gap with the proposed systematic review outlined in this protocol.…”

Section: Discussionmentioning

confidence: 99%

Antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children and adolescents: a systematic review protocol

2014

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BackgroundAbacavir 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.MethodsWe 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 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 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.DiscussionThe 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 registrationThis review is registered with PROSPERO, registration number CRD42014009157.

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“…cART only consisting of ABC/3TC/ZDV is generally not recommended as first‐line treatment because of suboptimal virological activity . However, a recent Cochrane review of the use of ABC/3TC/ZDV for initial treatment of HIV infection concluded that this regimen might still be useful, especially in patients with pre‐existing hyperlipidaemia and those not tolerating ritonavir . The combination of ABC/3TC/ZDV is also considered an acceptable alternative by the World Health Organization (WHO) in selected situations where standard cART is contraindicated or unavailable .…”

Section: Discussionmentioning

confidence: 99%

A randomized controlled trial of single‐class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96‐week results from the FREE study

et al. 2014

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ObjectivesThe aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI). MethodsAn open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/μL and HIV-1 RNA > 30 000 copies/mL (n = 207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA < 50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/μL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n = 61) or to continue the PI-based ART (n = 59). ResultsFor the proportions of patients (intention-to-treat; missing = failure) with HIV-1 RNA < 400 copies/mL (PI group, 66%; ABC/3TC/ZDV group, 71%) and < 50 copies/mL (PI group, 63%; ABC/ 3TC/ZDV group, 62%) at 96 weeks, switching to ABC/3TC/ZDV was noninferior compared with continuing the PI regimen; the difference in failure rate (ABC/3TC/ZDV minus PI) was −4.4 percentage points [95% confidence interval (CI) −21.0 to +12.3 percentage points] and +0.4 percentage points (95% CI −16.9 to +17.7 percentage points), respectively. In the per protocol analysis, the difference in virological failure for HIV-1 RNA > 400 copies/mL (0 of 39 patients in the PI group and two of 45 patients in the NRTI group) and for HIV-1 RNA > 50 copies/mL (two of 39 and three of 45 patients, respectively) was +4.4 percentage points (95% CI −2.1 to +11.0 percentage points) and +1.5 percentage points (95% CI −8.6 to +11.7 percentage points), respectively, also showing noninferiority. Serum lipids significantly improved in the NRTI group, but not in the PI arm.Correspondence: Dr HG Sprenger, University of Groningen, University Medical Center Groningen, Department of Internal Medicine AA41, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Tel: +31 50 361 2350; fax: +31 50 361 9069; e-mail: h.g.sprenger@umcg.nl DOI: 10.1111/hiv.12186 © 2014 British HIV Association HIV Medicine (2015, 16, 122-131 ORIGINAL RESEARCH 122 ConclusionsA single-class NRTI regimen after successful induction with standard ART had similar antiviral efficacy compared to continuation of a PI-based regimen at 96 weeks after baseline, with improved serum lipids. . Antiretroviral regimens frequently have to be adjusted because of toxicity, drug−drug interactions or pregnancy. Our hypothesis was that a triple NRTI regimen can be used safely as a maintenance regimen after successful virological suppression with standard cART. This study was initiated at a time when preferred regimens were still complex with a high pill burden and with more concerns about toxicity resulting in, for example, lipodystrophy.Initial studies addressing the effect of a switch to triple NRTIs included patients that had not been ART-naïve from the start, resulting in su...

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Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection and AIDS

Abstract: Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection and AIDS (Review)

Cited by 14 publications

References 43 publications

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis

Antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children and adolescents: a systematic review protocol

A randomized controlled trial of single‐class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96‐week results from the FREE study

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