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Laboratory data and prior pediatric reports indicate that HIV protease inhibitor (PI)–based antiretroviral therapy (ARV) kills gametocytes and reduces rates of gametocytemia, but not asymptomatic parasitemia, in a high malaria-transmission area. To determine whether ARV regimen impacts these rates in areas with less-intense malaria transmission, we compared asymptomatic parasitemia and gametocytemia rates in HIV-infected children by ARV regimen in Lilongwe, Malawi, an area of low-to-moderate transmission intensity. HIV PI lopinavir–ritonavir (LPV–rtv) ARV– or non-nucleoside reverse transcriptase inhibitor nevirapine ARV–treated children did not differ in the rates of polymerase chain reaction-detected asymptomatic parasitemia (relative risk [RR] 0.43 95% confidence interval [CI] [0.16, 1.18], P value 0.10) or microscopically detected gametocytemia with LPV–rtv ARV during symptomatic malaria (RR 0.48 95% CI [0.22,1.04] P value 0.06). LPV–rtv ARV was not associated with reduced rates of asymptomatic parasitemia, or gametocytemia on days of symptomatic malaria episodes, in HIV-infected children. Larger studies should evaluate whether ARV impacts transmission.

BackgroundHIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed.MethodsThirty-one children from Malawi aged 4-62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor.ResultsWe found an association between increased time to recurrent positive BS, but not CCM, when anti-malarial treatment and LPV-rtv based ART were used concurrently and when accounting for a LPV-rtv and antimalarial treatment interaction (adjusted HR 0.39; 95% CI (0.17,0.89); p = 0.03).ConclusionsLPV-rtv in combination with malaria treatment was associated with lower risk of recurrent positive BS, but not CCM, in HIV-infected children. Larger, randomized studies are needed to confirm these findings which may permit ART optimization for malaria-endemic settings.Trial registrationClinicalTrials.gov NCT00719602.

Aim: Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians. Materials & methods: CYP450 2B6, 2D6, 3A4 and 3A5, ABCB1 and constitutive androstane receptor and pregnane X receptor, were analyzed for polymorphisms in 26 subjects. Results: Allele frequencies (variant) were: CYP2B6 514G>T (0.31) CYP2D6*4 (0.02); CYP2D6*17 (0.35); CYP3A4*1B (0.77); CYP3A5*3 (0.25); ABCB1 2677G>T (0.0), ABCB1 3435C>T (0.21), NR1I3 13711152T>C (0.02), NR1I2 44477T>C (0.10), NR1I2 63396C>T (0.33), NR1I2 6-bp indel (del: 0.17). CYP2B6 516G>T (non-wild-type/wild-type) correlated with nevirapine pharmacokinetic parameters; geometric mean ratios (95% CI): 1.75 (1.27–2.40) for area under the concentration time curve (AUC)0–12 h, 1.58 (1.03–2.42) for C0, and 0.53 (0.31–0.91) for clearance. In a multivariable model, nevirapine AUC increased by 1.5% per year of age (p < 0.0001), CYP2B6 516 T allele increased AUC by 92% (p < 0.0001), and CYP3A5*3 decreased AUC by 31% (p = 0.0027). Conclusion: Allele frequencies were similar to other sub-Saharan African populations. The T allele for CYP2B6 516 was significantly associated with nevirapine exposure. Original submitted 15 June 2010; Revision submitted 5 July 2011

Our project, which concluded in 2015, aimed to improve the quality of life of children with life limiting illnesses in Maharashtra State in India, and nationwide in Malawi. Central to the project design was a multi team approach of engaging with expert model providers of children’s palliative care, global experts in children’s palliative care, national palliative care associations, and crucially, the children themselves. Six new sites were identified as being suitable for the incorporation of children’s palliative care into their existing service. The in-country team then developed and delivered training and mentorship to these new sites, building their capacity for children’s palliative care service delivery. The project also focused on advocacy to change restrictive policy, raise awareness and push for sustainable change. It was important to the project team that there was a strong element of beneficiary engagement with the project, both to strengthen the quality of the service and to provide a direct voice to policy makers. 4294 new children received palliative care in the six additional sites over the project period. Children in each setting joined ‘Empowerment Groups’ where they could share their experiences and discuss the changes to the services that were happening around them. These groups had a strong effect on the project, improving confidence and understanding both among the children and their carers, a feeling of support and shared experience. In one setting, the children’s group met directly with the minister of health and inspired her commitment to supporting palliative care for children. The groups gave direct feedback to service providers, allowing for changes in the approach. The empowerment groups were credited with increasing demand for services as caregivers were keen to share their knowledge in the community and in some cases, conducting active case finding and referral to the new services.

Introduction This project brings together partners from India, South Africa, Malawi and the UK to expand children’s palliative care services in Maharashtra state in India and in Malawi. The project results have prompted commitment to palliative care service development above and beyond the original project scope. It demonstrates how international partnerships can inspire and promote others to take on palliative care to meet the huge need for palliative care around the world. Methods The project uses international donor funds to integrate children’s palliative care into existing services in both urban and rural settings. Each partner brings to the project distinct skills and experience; ranging from project and donor management, paediatric palliative care knowledge, training and mentorship expertise, and advocacy skills. Results The mix of these skills has seen the following key results: The development of children’s palliative care services in 5 new settings. The integration of children’s palliative care into health service curricula. The inclusion of children’s palliative care in draft palliative care policy. The project has also prompted extended impact: The National Rural Health Mission (Jawhar, India) has committed to a wider programme of palliative care service delivery and is already funding training, staff and services. District hospitals in Malawi are showing strong interest in developing palliative care services Project stakeholders are increasingly seeking extra funding and gifts in kind to support and develop children’s palliative care services. Discussion The collaborative implementation of this project has proved to be a catalyst for further development of palliative care than originally anticipated. We would like to share our collaborative approach, together with more detailed results to inspire and encourage others to engage in partnerships to maximise impact and rise to the great challenge of meeting the huge need for palliative care internationally.

Introduction The project aims to support the development of children’s palliative care services across Malawi. The project aims to integrate children’s palliative care into existing service provision in 3 central hospitals. Aims In this piece of work within the project, the project team aim to empower children and their guardians to be involved in, and inform, decisions that are made about the provision of paediatric palliative care, at local and national level. Methods Regular empowerment workshops and focus group meetings are held with project beneficiaries (children and their guardians). An advocacy meeting was between child beneficiaries and the Minister for Health for Malawi. Learning and Results Empowerment meetings have resulted in patients and guardians feeling more informed about the care they receive and more in control. Focus group discussions with beneficiaries have resulted in changing practice at the services themselves. Empowerment meetings have been most successful when participants identify their own key concerns and have the space to explore solutions with others. Experience sharing and testimonies have played a great part in encouraging and learning from each other. The workshop with the project beneficiaries and Minister for Health allowed policy makers to hear first hand the experience of those living with life-limiting illnesses resulted in the minister pledging support to children’s palliative care in Malawi. The project is of interest to others who are working to support development of children’s palliative care. We would like to share our approach and learning with others, and to encourage discussion about participation and empowerment in any palliative care setting.