Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients

Briz, Verónica; Palladino, Claudia; Navarro, Ma Luisa; Ory, Santiago Jiménez de; González-Tomé, M I; García-León, Francisco Javier; Núñez-Cuadros, Esmeralda; José, MI De; Ramos, JT; Muñoz‐Fernández, María Ángeles

doi:10.1111/j.1468-1293.2010.00907.x

Cited by 22 publications

(16 citation statements)

References 6 publications

(7 reference statements)

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“…[6][7][8][9][10][11][12][13][14] In addition, DRV/r is not recommended in children <3 years of age owing to toxicity concerns in animal studies, and ETR, a second-generation NNRTI, is not recommended in children <6 years of age owing to lack of safety and efficacy data. Until very recently, DTG was only recommended by the US Food and Drug Administration (FDA) for adolescents >12 years of age and >40 kg body weight.…”

Section: Researchmentioning

confidence: 99%

Characteristics and early outcomes of children and adolescents treated with darunavir/ritonavir-, raltegravir- or etravirine-containing antiretroviral therapy in the Western Cape Province of South Africa

Nuttall

Pillay

2018

S Afr Med J

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RESEARCHBy 2012, the estimated number of children (0 -14 years of age) receiving antiretroviral therapy (ART) in South Africa (SA) was 140 541, representing an estimated 63% of those requiring treatment. [1,2] As increasing numbers of children are started on first-and second-line ART, the demand for third-line regimens in children and adolescents with treatment failure is likely to increase. It is estimated that currently <1% of people on ART globally are receiving third-line regimens, and it is unknown what proportion of these are children. [3] An unpublished systematic review presented in 2015 assessing second-and third-line ART options for children and adolescents concluded that there is insufficient evidence to directly evaluate alternative second-and third-line ART options for children, and that current recommendations are still based on inference from adult trials.[4] The World Health Organization (WHO) recommends that national programmes should develop policies for third-line ART that should incorporate integrase strand transfer inhibitors (INSTIs), second-generation protease inhibitors (PIs) and secondgeneration non-nucleoside reverse transcriptase inhibitors (NNRTIs) with minimal risk of cross-resistance to previously used regimens. Recommended third-line ART regimens in the WHO 2016 guidelines [5] are: (i) darunavir/ritonavir (DRV/r) plus dolutegravir (DTG) (or raltegravir (RAL)) with or without one to two nucleoside reverse transcriptase inhibitors (NRTIs); (ii) DRV/r plus two NRTIs with or without one NNRTI; or (iii) RAL (or DTG) plus two NRTIs, depending on the preceding first-and second-line ART regimens.Although safety and efficacy of DRV/r, etravirine (ETR) and RAL have been reported in specific age groups of ART-naive and ARTexperienced children and adolescents, there is a paucity of data on treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. [6][7][8][9][10][11][12][13][14] In addition, DRV/r is not recommended in children <3 years of age owing to toxicity concerns in animal studies, and ETR, a second-generation NNRTI, is not recommended in children <6 years of age owing to lack of safety and efficacy data. Until very recently, DTG was only recommended by the US Food and Drug Administration (FDA) for adolescents >12 years of age and >40 kg body weight.[15] The FDA has recently approved DTG from 6 to <12 years and ≥30 kg in a dose of 35 mg once daily, but suitable formulations that allow for administration of this dose are not yet registered in SA.[16] In SA, DTG has only been approved from 18 years of age. ObjectiveTo describe the characteristics and early outcomes of treatmentexperienced children and adolescents (<20 years of age) in the Western Cape Province of SA who initiated an ART regimen that included one or more of DRV/r, RAL and ETR. Background. There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, r...

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Section: Researchmentioning

confidence: 99%

Characteristics and early outcomes of children and adolescents treated with darunavir/ritonavir-, raltegravir- or etravirine-containing antiretroviral therapy in the Western Cape Province of South Africa

Nuttall

Pillay

2018

S Afr Med J

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“…Construction of effective third‐line and subsequent regimens, ideally with at least two and preferably three fully active agents, requires expert advice. Paediatric experience of combinations that include INSTIs 189, T20 190, ETR 191, 192, MVC 132 and DRV/r is accumulating.…”

Section: When To Switch Resistance Testing and Second And Subsequentmentioning

confidence: 99%

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

et al. 2015

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The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

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“…All four children who failed to respond to etravirine-based therapy were found to harbor mutations associated with etravirine resistance (E138A, Y181I, G190A, and K101E with G190A/S). 48 Etravirine was well tolerated with no significant adverse reactions reported. Five of the 18 adolescents (27.8%) developed a rash, although this did not lead to discontinuation of the drug.…”

Section: Safety and Efficacy Of Etravirine In Childrenmentioning

confidence: 99%

“…Briz et al retrospectively described the use of etravirine in 23 HIV-infected pediatric patients in a multicenter study. 48 Five antiretroviral-experienced children aged 5-12 years and 18 adolescents aged 13-18 years, all but one of whom had evidence of genotypic NNRTI resistance and had failed therapy with either efavirenz or nevirapine, were retrospectively assessed after etravirine was added to their failing antiretroviral regimen. Children received etravirine at 5.2 mg/kg twice daily and adolescents at 200 mg twice daily.…”

Section: Safety and Efficacy Of Etravirine In Childrenmentioning

confidence: 99%

Profile of etravirine in the treatment of HIV in pediatrics

Dehority¹,

Viani

2013

PHMT

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Etravirine is a non-nucleoside reverse transcriptase inhibitor now licensed for treatment of human immunodeficiency virus (HIV)-1 infection in both children over 6 years of age and adults. Etravirine demonstrates a high genetic barrier to the development of resistance, as multiple mutations are typically required prior to the onset of reduced susceptibility to the drug. It retains in vitro and clinical activity against many HIV-1 isolates, demonstrating resistance to other non-nucleoside reverse transcriptase inhibitors, such as efavirenz and nevirapine. Given the ability of HIV to develop resistance rapidly across the non-nucleoside reverse transcriptase inhibitor class of antiretrovirals, etravirine has a welcome place in the management of HIVinfected patients, particularly treatment-experienced individuals harboring non-nucleoside reverse transcriptase inhibitor mutations. Etravirine has been shown to improve CD4 counts and viral load significantly in HIV-infected adults on combination antiretroviral therapy when compared with placebo in a large, randomized controlled trial. Data on the utility of etravirine in children are still somewhat limited, although a recent pediatric trial has demonstrated adequate pharmacokinetics, safety, and efficacy of etravirine in a small number of HIV-infected children and adolescents. In both children and adults, rash appears to be the most common adverse effect described. Despite its high genetic barrier to resistance, evidence of mutations conferring etravirine resistance has been documented in both adult and pediatric patients. Such mutations have been best described in treatment-experienced populations, including those who have never been exposed to the drug. This review describes the existing literature on the use of etravirine in the pediatric population, and highlights future and ongoing directions of investigation.

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Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients

Cited by 22 publications

References 6 publications

Characteristics and early outcomes of children and adolescents treated with darunavir/ritonavir-, raltegravir- or etravirine-containing antiretroviral therapy in the Western Cape Province of South Africa

Characteristics and early outcomes of children and adolescents treated with darunavir/ritonavir-, raltegravir- or etravirine-containing antiretroviral therapy in the Western Cape Province of South Africa

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

Profile of etravirine in the treatment of HIV in pediatrics

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