Improving treatment outcome for children with HIV

Calmy, Alexandra; Ford, Nathan

doi:10.1016/s0140-6736(11)60363-2

Cited by 7 publications

(8 citation statements)

References 10 publications

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“…[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. [107] …”

Section: Discussionmentioning

confidence: 99%

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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%

“…Access to routine plasma HIV-1 RNA load monitoring is crucial and necessary, [30,107,115–119] although difficult in resource-constrained countries, [120] in addition to the use of potent PI-based regimens and adapted formulations for the different age classes.…”

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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“…Successful third-line therapy of paediatric patients is hindered by the lack of paediatric formulations and high costs, with dosing especially problematic for children younger than six years, largely a result of the low priority that is given globally to the development of paediatric formulations and regimens [26]. 3TC monotherapy and other sub-optimal interim measures, although being used in some resource-limited settings, are not evidence based, whereas continued PI therapy, even when it does not achieve virological success, could nevertheless render immunological and clinical benefit in children [27], but at the potential cost of resistance accumulation.…”

Section: Discussionmentioning

confidence: 99%

It is time to consider third‐line options in antiretroviral‐experienced paediatric patients?

Zyl

Rabie

Nuttall

et al. 2011

Journal of the International AIDS Society

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BackgroundThe historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations.MethodsIn order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations.ResultsFourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance.ConclusionsIn children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy.

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“…Children also depend on others to receive medication and clinic follow-ups. Treatment durability is, however, more crucial in children than in adults, and young children failing to achieve virological suppression is an important concern (Calmy & Ford, 2011).…”

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confidence: 99%

Improved virological suppression in children on antiretroviral treatment receiving community-based adherence support: A multicentre cohort study from South Africa

et al. 2013

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Adherence to antiretroviral treatment (ART) is a challenge in childhood, and children on ART have reduced virological suppression compared to adults. This study evaluated the effect of community-based adherence support (CBAS) on virological outcomes amongst children receiving ART in four South African provinces. Patient Advocates are lay CBAS workers who provide adherence and psychosocial support for patients, undertaking home visits to address household challenges affecting adherence. Patient Advocates provide counselling for children's carers regarding adherence and psychosocial problems. A multicentre cohort study using routinely collected data was conducted at 57 public ART sites including ART-naive children (<16 years) starting ART. Virological suppression until four years of ART was compared between children who received and did not receive CBAS. Analyses were by intention-to-treat, controlling for confounding using multivariable generalised estimating equations. A total of 4853 children were included, of whom 982 (20.2%) received CBAS. The median baseline age was 6.3 years and the baseline CD4 cell percentage was 12.0%; both were equivalent between the two groups. CBAS children had more advanced baseline clinical disease (62.1% vs. 52.6% World Health Organisation stages III or IV; P < 0.0001). A total of 5908 viral load results were analysed. Virological suppression was 65.6% (95% confidence interval [CI]: 62.7-68.4%) vs. 55.5% (95% CI: 54.1-57.0%) in CBAS and non-CBAS children, respectively, at any time-point on treatment (P < 0.0001). In analyses controlling for baseline clinical, demographic, site-related variables and time on ART, children receiving CBAS were more likely to achieve virological suppression, adjusted odds ratio (aOR) 1.60 (95% CI: 1.35-1.89; P < 0.0001). The effect of CBAS increased in magnitude with increasing durations of ART, and CBAS particularly improved virological suppression in a higher-risk subgroup (children younger than two years, aOR 2.47 [95% CI: 1.59-3.84]). CBAS was associated with improved virological suppression in children receiving ART. Expanded implementation of this low-cost intervention should be considered in resource-poor settings.

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Improving treatment outcome for children with HIV

Cited by 7 publications

References 10 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

It is time to consider third‐line options in antiretroviral‐experienced paediatric patients?

Improved virological suppression in children on antiretroviral treatment receiving community-based adherence support: A multicentre cohort study from South Africa

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