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

ABSTRACT: 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.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 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of included studies, search relevant conference proceedings, email the authors of included studies and also look for unpublished and ongoing trials in prospective clinical trial registries.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.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.This review is registered with PROSPERO, registration number CRD42014009157.

SUBMITTER: Adetokunboh OO

PROVIDER: S-EPMC4137106 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Project description:WHO recommends ritonavir-boosted protease inhibitor with two nucleoside reverse transcriptase inhibitors in HIV-infected patients failing non-nucleoside reverse transcriptase inhibitor-based first-line treatment. Here, we aimed to provide more evidence for the choice of nucleoside reverse transcriptase inhibitor and boosted protease inhibitor.ANRS 12169 is a 48-week, randomized, open-label, non-inferiority trial in three African cities, comparing efficacy and safety of three second-line regimens.Patients failing non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy with confirmed plasma HIV-1 viral load above 1000?copies/ml were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (control group as per WHO recommendations), abacavir + didanosine + lopinavir/ritonavir (ABC/ddI group) or tenofovir/emtricitabine + darunavir/ritonavir (DRV group) regimens. The primary endpoint was the proportion of patients with plasma vral load below 50?copies/ml at week 48 in the modified intention-to-treat population. Non-inferiority was pre-specified with a 15% margin.Of the 454 randomized patients, 451 were included in the analysis. Globally, 294 (65.2%) and 375 (83.2%) patients had viral load below 50 and 200?copies/ml, respectively, at week 48. The primary endpoint was achieved in 105 (69.1%) control group patients versus 92 (63.4%) in the ABC/ddI (difference 5.6%, 95% confidence interval -5.1 to 16.4) and 97 (63.0%) in the DRV (difference 6.1%, 95% confidence interval -4.5 to 16.7) groups (non-inferiority not shown). Overall, less number of patients with baseline viral load at least 100?000?copies/ml (n?=?122) had a viral load below 50?copies/ml at week 48 (37.7 versus 75.4%; P?<?0.001).The three second-line regimens obtained similar and satisfactory virologic control and confirmed the WHO recommendation (TDF/FTC/LPVr) as a valid option. However, the suboptimal response for patients with high viral load warrants research for improved strategies.

Project description:IntroductionIn April 2010, tenofovir and abacavir replaced stavudine in public sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for paediatric patients 3-19 years of age at eight public sector clinics in Johannesburg, South Africa.MethodsCohort analysis of treatment-naïve, non-pregnant paediatric patients from 3 to 19 years old initiated on ART between April 2004 and December 2013. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine after April 2010 in first-line ART. We evaluated the frequency and type of single-drug substitutions, treatment interruptions and switches to second-line therapy. Fine and Gray competing risk regression models were used to evaluate the association of antiretroviral drug type with single-drug substitutions, treatment interruptions and second-line switches in the first 24 months on treatment.ResultsThree hundred and ninety-eight (15.3%) single-drug substitutions, 187 (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy occurred among 2602 paediatric patients over 24-months on ART. Overall, the rate of single-drug substitutions started to increase in 2009, peaked in 2011 at 25% and then declined to 10% in 2013, well after the integration of tenofovir into paediatric regimens; no patients over the age of 3 were initiated on abacavir for first-line therapy. Competing risk regression models showed patients on zidovudine or stavudine had upwards of a fivefold increase in single-drug substitution vs. patients initiated on tenofovir in the first 24 months on ART. Older adolescents also had a two- to threefold increase in treatment interruptions and switches to second-line therapy compared to younger patients in the first 24 months on ART.ConclusionsThe decline in single-drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.

Project description:BACKGROUND:The anti-retroviral combination of abacavir/lamivudine plus rilpivirine (ABC/3TC/RPV) is not recommended by international guidelines as the first-line regimen. However, it is potent, well-tolerated, and affordable, especially in resource-limited settings. This study evaluates the efficacy and safety of ABC/3TC/RPV as an initial regimen for treatment-naïve HIV-1 infected patients. METHODS:A retrospective study was conducted in the largest HIV care centre in Singapore, with data collected June 2011 to September 2017. All treatment-naïve HIV-1 infected adults prescribed ABC/3TC as part of their initial anti-retroviral therapy regimen were included. The third drug was a non-nucleoside reverse-transcriptase inhibitor (NNRTI) such as RPV or efavirenz (EFV), or boosted protease-inhibitor (PI). Patients were followed up for 48 weeks. The primary end-point was the percentage of patients achieving virologic suppression, analysed using on-treatment analysis. Secondary outcomes included CD4-count change, treatment discontinuation and treatment-related adverse events. RESULTS:170 patients were included in the study, 66 patients in the RPV group, 104 patients in the comparator group (EFV or boosted PI). 96% (n?=?24) in the RPV group and 87% (n?=?26) in the comparator group achieved viral suppression at 48 weeks (p?=?0.28). Median (interquartile range) time to viral suppression was similar: 17 (14-24) weeks in the RPV group, and 21 (13-26) weeks in the comparator group. There were no statistically significant differences in the CD4 count between the two groups. 14% (n?=?9) of patients on RPV discontinued treatment before 48 weeks, compared to 30% (n?=?31) from the comparator group (p?=?0.053). Of these, 23 discontinuations were due to drug adverse effects, and only 1 attributed to RPV (p?<?0.01). One patient in each group had virologic failure. CONCLUSION:RPV is effective, safe and considerably more tolerable than compared to NNRTI or boosted PI in ABC/3TC-containing regimens for treatment-naïve patients. It offers an affordable and attractive option, especially in resource-limited settings.

Project description:The ability to continue combination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-infected patients undergoing hematopoietic cell transplantation (HCT) for treatment of hematologic malignancies is likely a critical factor in preventing the establishment of an HIV reservoir in transplanted stem cells. Thus, we studied the feasibility of continued antiretroviral therapy in our HIV-infected patients undergoing autologous or allogeneic transplantation. All HIV-infected adults undergoing HCT for hematologic malignancy at Fred Hutchinson Cancer Research Center between 2006 and 2014 were included; most were enrolled in a prospective clinical study to monitor HIV reservoirs after transplantation (NCT00968630 and NCT00112593). Non-nucleotide reverse transcriptase inhibitor or integrase-strand inhibitor-anchored antiretroviral therapy regimens were continued or selected before HCT by infectious disease physicians. Plasma HIV RNA was measured every other day for the first 2 weeks after transplantation and then every 2 weeks. Missed doses of cART and reasons for changing the cART regimen during the post-transplantation hospitalization were documented through review of inpatient pharmacy records. Seven autologous and 8 allogeneic transplantations were performed. In 9 transplantations, the cART regimen was not altered after HCT and no doses were missed. In 2 patients who required alterations in their cART regimen because of development of acute renal failure (n = 1) and small bowel obstruction (n = 1) after HCT, enfuvirtide was used as a bridging component of the regimen. Plasma HIV RNA remained suppressed during the first 28 days in 12 of 15 transplantations, and no patients had a plasma HIV RNA >1000 copies/mL during long-term follow up. Non-nucleotide reverse transcriptase inhibitor- and integrase-strand inhibitor-based cART are safe and effective in HIV-infected persons during the peri-HCT period. Most patients undergoing HCT were able to continue cART without missed doses. Sustained HIV viremia and emergence of resistance were not detected.

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

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