Early Outcomes of Darunavir- and/or Raltegravir-Based Antiretroviral Therapy in Children with Multidrug-Resistant HIV at a Pediatric Center in Botswana

Kirk, Brianna; Gomila, Andres; Matshaba, Mogomotsi; Marape, Marape; Joel, Dipesalema R.; Anabwani, Gabriel; Tolle, Michael A.

doi:10.1177/1545109712463073

Cited by 9 publications

(3 citation statements)

References 12 publications

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“… 10 By leveraging the considerable resources and experience of a comprehensive pediatric HIV program in Botswana, PHO services were developed at PMH. 4 , 11 - 13 This initial report of the BPOD demonstrates that pediatric cancer distribution in Botswana appears more similar to reports from the United States or Europe than to other institutional African reports, and that diagnostic and treatment capacity can be developed in a resource-limited setting during a short period of time through collaboration between government and international partnerships.…”

Section: Discussionmentioning

confidence: 63%

Establishing a Pediatric Hematology-Oncology Program in Botswana

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Wally

et al. 2018

JGO

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PurposeAnnually, 300,000 children are diagnosed with cancer, and the majority of these children live in low- and middle-income countries (LMICs). Currently, there is incomplete information on pediatric cancer incidence, diagnosis distribution, and treatment outcomes in Africa. Since 2007, a pediatric hematology-oncology program has been operating in Botswana through a partnership between the Botswana government, Baylor College of Medicine, and Texas Children’s Hospital.MethodsTo better understand patient characteristics and outcomes at Botswana’s only pediatric cancer program, a hospital-based data base—the Botswana Pediatric Oncology Database—was established in 2014. Children younger than 18 years of age at the time of diagnosis who presented between 2008 and 2015 were included. Data for this study were extracted in February 2016.ResultsOf the 240 potential enrollees, 185 (77%) children met eligibility for this study. The median age was 6.4 years, and 50.8% were male. Leukemia was the most common malignancy representing 18.9% of the cohort and 88.1% of the total cohort had a histopathologic diagnosis. HIV seropositivity was confirmed in 13.5%. The 2-year overall survival of all pediatric cancer diagnoses was 52.4%. Abandonment of treatment occurred in 3.8% of patients.ConclusionIn the first 9 years of the program, capacity has been developed through a longstanding partnership between Botswana and Baylor College of Medicine/Texas Children’s Hospital that has led to children receiving care for cancer and blood disorders. Although continued improvements are necessary, outcomes to date indicate that children with cancer in Botswana can be successfully diagnosed and treated.

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Section: Discussionmentioning

confidence: 63%

Establishing a Pediatric Hematology-Oncology Program in Botswana

Slone

Wally

et al. 2018

JGO

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“…All patients who achieved viral suppression showed improved or stable CD4 + cell counts, even after long-standing treatment failure. At the end of this study, all of the patients in this report were classified as having a WHO class 1 HIV infection, and they did not present opportunistic infections during the study; however, the prescription of an effective combination therapy for HIV-infected children harboring an MDR virus is one of the greatest challenges in the clinical management of children with HIV infection (11,12). In this study, the basal sample had a susceptibility to DRV, Tipranavir (TPV), Etravirine (ETV), and Tenofovir (TDF) of 87, 37, 87, and 50%, respectively, according to the Stanford HIVdb; in addition, RAL was considered to be fully active.…”

Section: Discussionmentioning

confidence: 99%

Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection

et al. 2016

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Background: Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low-and middle-income countries. Methods: Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data. The primary end point was virological suppression (<50 copies/ml) and immunological improvement after 48 wk of treatment with the new ART regimen. results: The median age of the patients was 14.5 y (interquartile range (IQR) 11-16.5). Median HIV-1 RNA viral load was 4.2 log 10 (IQR: 3.4-4.8). The primary end point was found in 11 children (69%), and 13 children (81%) had an HIV-1 RNA viral load <200 copies/ml. Median (IQR) for the baseline CD4 + cell count was 382 cells/μl (281-686 cells/μl), whereas after 48 wk of treatment with the new ART regimen, it was 640 cells/μl (361-936 cells/μl) (P < 0.001). conclusion: Darunavir/ritonavir, raltegravir, and etravirine were well tolerated in the present pediatric population. These drugs provide good options for children exposed to extensive ART. Regimens guided by genotyping data were effective for children who had ART failure and multidrug-resistant HIV-1 infection.i nfants and children who were infected perinatally are now surviving to adulthood with lifelong HIV infection and longterm exposure to combined antiretroviral therapy (ART) (1). Data from the United Kingdom Collaborative HIV Pediatric Study cohort demonstrated that over one-third of children had experienced virological treatment failure and were on a second or subsequent line of therapy at the time of their transition to adult care (2). In the pediatric setting, virological treatment failure occurs most frequently because of poor adherence to ART, and whenever viral replication is inefficiently controlled, virological treatment failure occurs more quickly, allowing the selection of HIV-1 quasispecies resistant to antiretroviral (ARV) drugs (3).Many innate and external factors have been associated with HIV drug resistance mutations in children, such as being infected perinatally, and extremely high viral load during the first steps of the infection, which can take longer to suppress than that in older children or adults, even when they are on fully active ART regimens (4).Interpretation of resistance tests in this context can be complex, particularly in the presence of expanding options for ARV drugs, and treatment decisions should be made with the support of pharmacists and clinicians who have expertise in the field (5).Currently, more than 20 different ARV drugs with six different classes of action have been approved for use in children or adolescents with HIV infection worldwide; most of them are used in Mexico (6).A good level of adherence is particularly difficult during adolescence, especially with a complex regimen ...

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“…Development of newer pediatric fixed-dose formulations (e.g., TDF/3TC/EFV) will also facilitate greater harmonization, as would better tolerated and more potent NNRTI-sparing regimens that could mitigate adherence issues secondary to LPV/r intolerance. In addition, raltegravir and ritonavir-boosted darunavir have been used successfully among children in LMICs that have developed LPV/r-resistance (42) and the recent approval of dalutegravir for children >12 years is another promising development (43). These advances are collectively expanding the availability of newer approaches to ART therapy in children, and will certainly influence future guidelines for pediatric treatment.…”

Section: A Public Health Approach To Pediatric Hivmentioning

confidence: 99%