Articles tagged as "Paediatric"

Can nevirapine-exposed children switch to efavirenz?

Efavirenz-based antiretroviral therapy among nevirapine-exposed HIV-infected children in South Africa: a randomized clinical trial.

Coovadia A, Abrams EJ, Strehlau R, Shiau S, Pinillos F, Martens L, Patel F, Hunt G, Tsai WY, Kuhn L. JAMA. 2015 Nov 3;314(17):1808-17. doi: 10.1001/jama.2015.13631.

Importance: Advantages of using efavirenz as part of treatment for children infected with human immunodeficiency virus (HIV) include once-daily dosing, simplification of co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for second-line treatment, and harmonization of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission.

Objective: To evaluate whether nevirapine-exposed children achieving initial viral suppression with ritonavir-boosted lopinavir-based therapy can transition to efavirenz-based therapy without risk of viral failure.

Design, setting, and participants: Randomized, open-label noninferiority trial conducted at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa, from June 2010 to December 2013, enrolling 300 HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission who were aged 3 years or older and had plasma HIV RNA of less than 50 copies/mL during ritonavir-boosted lopinavir-based therapy; 298 were randomized and 292 (98%) were followed up to 48 weeks after randomization.

Interventions: Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148).

Main outcomes and measures: Risk difference between groups in (1) viral rebound (ie, ≥1 HIV RNA measurement of >50 copies/mL) and (2) viral failure (ie, confirmed HIV RNA >1000 copies/mL) with a noninferiority bound of -0.10. Immunologic and clinical responses were secondary end points.

Results: The Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n = 26) in the efavirenz group and 0.284 (n = 42) in the ritonavir-boosted lopinavir group. Probabilities of viral failure were 0.027 (n = 4) in the efavirenz group and 0.020 (n = 3) in the ritonavir-boosted lopinavir group. The risk difference for viral rebound was 0.107 (1-sided 95% CI, 0.028 to infinity) and for viral failure was -0.007 (1-sided 95% CI, -0.036 to infinity). We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end points. By 48 weeks, CD4 cell percentage was 2.88% (95% CI, 1.26%-4.49%) higher in the efavirenz group than in the ritonavir-boosted lopinavir group.

Conclusions and relevance: Among HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission and with initial viral suppression with ritonavir-boosted lopinavir-based therapy, switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound or viral failure. This therapeutic approach may offer advantages in children such as these.

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Editor’s notes: For infants and young children (aged under three years), World Health Organization recommends ritonavir-boosted lopinavir therapy as the first-line antiretroviral therapy regimen. This is because of concerns about the increased risk of virologic failure with non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimens among infants previously exposed to NNRTIs for prevention of mother-to-child HIV transmission, and better virologic efficacy of a lopinavir-based regimen even in unexposed HIV-positive infants and young children. However, there are several significant issues associated with use of boosted lopinavir therapy in children. Firstly, the syrup form of the drug has an unpleasant taste posing major adherence challenges. Secondly, there are pharmacokinetic constraints restricting its use in children who are also being treated for tuberculosis. Thirdly, there are metabolic toxicities associated with the use of boosted lopinavir therapy.

In this open-labelled non-inferiority trial, the investigators examined whether efavirenz can be used in children aged over three years, previously exposed to nevirapine as part of prevention of mother-to-child HIV transmission, who have achieved virologic suppression with lopinavir-based therapy. Efavirenz was found to be non-inferior for both the trial endpoints, namely risk of viral rebound and risk of virologic failure. There were no differences in CD4 counts or other clinical endpoints such as height- or weight-for age, anaemia or neutropenia, skin reactions or serious elevations in transaminases between the groups. In addition, children randomised to switch to efavirenz had a significantly better lipid profile than people who continued to take lopinavir-based therapy. Children randomised to receive efavirenz had significantly higher rates of neuropsychiatric disturbances, but these did not persist beyond eight weeks and notably there were no differences in proportions with behavioural problems between the two arms at the end of follow-up.

The findings of this study strongly support the switch to efavirenz in children who have achieved virologic suppression. Some caveats of this study are that the findings cannot be generalised to children who are aged under three years or to children failing boosted lopinavir therapy. In addition, it is not clear how long children can be maintained on lopinavir-based therapy before a switch to efavirenz can be made.

There is currently no guidance on managing children aged over three years taking lopinavir therapy. This study provides strong evidence to support the switch to efavirenz among virally-suppressed children aged over three years. This is important given the considerable advantages of efavirenz, including preservation of protease inhibitor-based regimens for second line treatment, harmonising paediatric with adult guidelines that recommend efavirenz as first-line therapy, once-daily dosing, better palatability and lower cost.

South Africa
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Using storybooks to tell children about their HIV in Namibia: what works

Growing-up just like everyone else: key components of a successful pediatric HIV disclosure intervention in Namibia.

Brandt L, Beima-Sofie K, Hamunime N, Shepard M, Ferris L, Ingo P, John-Stewart G, O'Malley G. AIDS. 2015 Jun;29 Suppl 1:S81-9. doi: 10.1097/QAD.0000000000000667.

Objectives: To facilitate replication and adaptation of pediatric HIV disclosure interventions, we identified key components of a child-friendly cartoon book used to guide Namibian caregivers and healthcare workers (HCWs) through a gradual, structured disclosure process.

Design: Qualitative interviews were conducted with caregivers and HCWs from four high-volume pediatric HIV clinics in Namibia.

Methods: Semi-structured in-depth interviews with 35 HCWs and 64 caregivers of HIV+ children aged 7-15 were analyzed using constant comparative and modified grounded theory analysis. Major barriers to disclosure were compared to accounts of intervention success, and themes related to key components were identified.

Results: The disclosure book overcomes barriers to disclosure by reducing caregiver resistance, increasing HIV and disclosure knowledge, and providing a gradual, structured framework for disclosure. The delayed mention of HIV-specific terminology overcomes caregiver fears associated with HIV stigma, thus encouraging earlier uptake of disclosure initiation. Caregivers value the book's focus on staying healthy, keeping the body strong, and having a future 'like other kids', thus capitalizing on evidence of the positive benefits of resilience and hopefulness rather than the negative consequences of HIV. The book's concepts and images resonate with children who readily adopt the language of 'body soldiers' and 'bad guys' in describing how important it is for them to take their medicine. Discussion cues ease communication between HCWs, caregivers, and pediatric patients.

Conclusion: Given the urgent need for available pediatric HIV disclosure interventions, easily implementable tools like the Namibian disclosure book should be evaluated for utility in similar settings.

Abstract access 

Editor’s notes: There is clear guidance from global and national policy that school-aged children should be fully disclosed to about their positive HIV status. However in reality disclosure to children continues to be done at a much later stage and in an incomplete way. Simple activities are necessary to support carers to disclose, equipping them with appropriate ways to tell children what they need to know about their HIV status and the nature of their condition. This paper presents the findings from a qualitative study evaluating a child-friendly storybook activity in Namibia designed to facilitate and ease the challenges carers face in timely and full disclosure to children. 

Both the caregivers and the healthcare workers reported that the book helped them overcome many of the barriers to disclosure. This finding suggests that the activity has considerable potential. The empirical literature focuses heavily on the reasons behind delayed disclosure including guilt, fear, and inadequate knowledge about how to approach and explain the topic. The particular value of this study is the contribution the authors are able to make to our understanding of what works to overcome these barriers to disclosure and why. They focus in particular on the use of metaphor within a narrative and the positive impact of a particular health behaviour (treatment adherence) in helping children to ameliorate the significance of the condition itself in their physical and social lives. What contributes to the success and applicability of the programme is that these books are designed to address common challenges faced by paediatric HIV clinics in resource-stretched settings with relative ease. For example the challenges posed by inconsistent caregivers accompanying the child to the clinic or the pressing demands on a healthcare worker’s time in a busy clinic.

The evidence presented in this paper is based on self-report from the healthcare workers and carers. The study suggests that there would be considerable value in evaluating this programme through larger studies to assess its efficacy. However, in addition to that, asking children themselves, who have been exposed to the book, about their experiences in any future research would further strengthen our understanding of the impact of the programme in this setting.  Involving the children in the research would inform how the programme can be refined and adapted for other settings. 

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