Antiretroviral Therapy for Children in Resource-Limited Settings

Eley, Brian; Meyers, Tammy

doi:10.2165/11593330-000000000-00000

Cited by 9 publications

(9 citation statements)

References 64 publications

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“…[104] The best choice could be a salvage potent PI with high genetic barrier to resistance, such as DRV/r. [82,104,105] Recent data has shown that integrase inhibitors such as raltegravir and elvitegravir are also valuable in pediatric treatment. [104–106] Finally, successful 3rd-line therapy of pediatric patients is hindered by the lack of pediatric formulations and high costs, with dosing especially problematic for children younger than 6 years, largely a result of the low priority that is given globally to the development of pediatric formulations and regimens.…”

Section: Discussionmentioning

confidence: 99%

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

et al. 2017

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A large cohort of 220 HIV-1-infected children (median [range] age: 12 [4–17] years) was cared and followed up in the Central African Republic, including 198 in 1st-line and 22 in 2nd-line antiretroviral regimens. Patients were monitored clinically and biologically for HIV-1 RNA load and drug resistance mutations (DRMs) genotyping. A total of 87 (40%) study children were virological responders and 133 (60%) nonresponders. In children with detectable viral load, the majority (129; 97%) represented a virological failure. In children receiving 1st-line regimens in virological failure for whom genotypic resistance test was available, 45% displayed viruses harboring at least 1 DRM to NNRTI or NRTI, and 26% showed at least 1 major DRM to NNRTI or NRTI; more than half of children in 1st-line regimens were resistant to 1st-generation NNRTI and 24% of the children in 1st-line regimens had a major DRMs to PI. Virological failure and selection of DRMs were both associated with poor adherence. These observations demonstrate high rate of virological failure after 3 to 5 years of 1st-line or 2nd-line antiretroviral treatment, which is generally associated with DRMs and therapeutic failure. Overall, more than half (55%) of children receiving 1st-line antiretroviral treatment for a median of 3.4 years showed virological failure and antiretroviral-resistance and thus eligible to 2nd-line treatment. Furthermore, two-third (64%) of children under 2nd-line therapy were eligible to 3rd-line regimen. Taken together, these observations point the necessity to monitor antiretroviral-treated children by plasma HIV-1 RNA load to diagnose as early as possible the therapeutic failure and operate switch to a new therapeutic line.

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Section: Discussionmentioning

confidence: 99%

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

et al. 2017

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“…This increased access to first-line ART in children means that, over time, more children will fail first-line regimens and require second-line ART, particularly in poorly monitored or rural clinics [17], [18]. Unfortunately, in many resource-limited settings, access to second-line pediatric ART is challenging and options are very limited [19].…”

Section: Discussionmentioning

confidence: 99%

“…Given the intermediate level of transmitted NNRTI resistance and evidence of inferior viral suppression when used as first or second-line ART, this currently leaves limited options for children in South Africa after they fail PI-based first- or second-line therapy. Although Darunavir and Tipranavir have shown promising efficacy with limited toxicity in treatment-experienced children with significant PI resistance mutations, unfortunately these agents are not widely accessible to children in South Africa or other resource-limited settings at this time [19], [29], [30].…”

Section: Discussionmentioning

confidence: 99%

Pediatric Response to Second-Line Antiretroviral Therapy in South Africa

2012

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BackgroundWith improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure.MethodsWe performed a retrospective cohort analysis using electronic medical records from HIV-infected children who initiated ART at McCord Hospital's Sinikithemba Clinic in KwaZulu-Natal, South Africa, from August 2003 to December 2010. We analyzed all records from children who began second-line ART due to first-line treatment failure. We used logistic regression to compare viral outcomes in Protease Inhibitor (PI)-based versus Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based second-line ART, controlling for time on first-line ART, sex, and whether HIV genotyping guided the regimen change.ResultsOf the 880 children who initiated ART during this time period, 80 (9.1%) switched to second-line ART due to therapeutic failure of first-line ART after a median of 95 weeks (IQR 65–147 weeks). Eight (10%) of the failures received NNRTI-based second-line ART, all of whom failed a PI-based first-line regimen. Seventy (87.5%) received PI-based second-line ART, all of whom failed a NNRTI-based first-line regimen. Two children (2.5%) received non-standard dual therapy as second-line ART. Six months after switching ART regimens, the viral suppression rate was significantly higher in the PI group (82%) than in the NNRTI group (29%; p = 0.003). Forty-one children (51%) were tested for genotypic resistance prior to switching to second-line ART. There was no significant difference in six month viral suppression (p = 0.38) between children with and without genotype testing. Conclusion: NNRTI-based second-line ART carries a high risk of virologic failure compared to PI-based second-line ART.

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“…This finding in children without NVP exposure has major implications since LPV/r is more expensive, the liquid formulation requires refrigeration, and it is less palatable than NVP. 8 Our objectives were to investigate whether the differences between NVP- and LPV/r-based ART observed in children with PrNVP differed significantly from those with no PrNVP, identify other predictors of virologic and clinical response, and determine whether treatment differences depended on these other predictors.…”

mentioning

confidence: 99%

Predictors of Virologic and Clinical Response to Nevirapine versus Lopinavir/Ritonavir-based Antiretroviral Therapy in Young Children With and Without Prior Nevirapine Exposure for the Prevention of Mother-to-child HIV Transmission

Lindsey

Hughes

Violari

et al. 2014

Pediatric Infectious Disease Journal

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Background In a randomized trial comparing nevirapine (NVP)- versus lopinavir/ritonavir (LPV/r)– based antiretroviral therapy (ART) in HIV-infected children (primary endpoint discontinuation of study treatment for any reason or virologic failure (VF) by week 24) aged two months to three years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates. Methods Efficacy was assessed by time to ART discontinuation or VF, VF/death, and death; safety by time to ART discontinuation due to a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height WHO z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates. Results Over a median follow-up of 48 (PrNVP) and 72 (No PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r – based ART was superior to NVP-based ART for efficacy and safety outcomes but those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pre-treatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pre-treatment CD4% with shorter time to ART discontinuation due to a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥3 adverse event. Conclusions Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breastfeeding, sex, HIV-1 subtype, age, pre-treatment CD4%, HIV-1 RNA or WHO disease stage. This finding should be considered when selecting an ART regimen for young children.

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Antiretroviral Therapy for Children in Resource-Limited Settings

Cited by 9 publications

References 64 publications

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

High levels of virological failure with major genotypic resistance mutations in HIV-1-infected children after 5 years of care according to WHO-recommended 1st-line and 2nd-line antiretroviral regimens in the Central African Republic

Pediatric Response to Second-Line Antiretroviral Therapy in South Africa

Predictors of Virologic and Clinical Response to Nevirapine versus Lopinavir/Ritonavir-based Antiretroviral Therapy in Young Children With and Without Prior Nevirapine Exposure for the Prevention of Mother-to-child HIV Transmission

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