for Medecins Sans Frontieres. In resource-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretroviral therapy

Doctors Without Borders, Lutetia Parisorum, Île-de-France, France
AIDS (Impact Factor: 5.55). 10/2006; 20(15):1955-60. DOI: 10.1097/01.aids.0000247117.66585.ce
Source: PubMed


To (a) determine early treatment outcomes and (b) assess safety in children treated with adult fixed-dose combination (FDC) antiretroviral tablets.
Sixteen Medecins Sans Frontieres (MSF) HIV programs in eight countries in resource-limited settings (RLS).
Analysis of routine program data gathered June 2001 to March 2005.
A total of 1184 children [median age, 7 years; inter-quartile range (IQR), 4.6-9.3] were treated with antiretroviral therapy (ART) of whom 616(52%) were male. At ART initiation, Centres for Disease Control stages N, A, B and C were 9, 14, 38 and 39%, respectively. Children were followed up for a median period of 6 months (IQR, 2-12 months). At 12 months the median CD4 percentage gain in children aged 18-59 months was 15% (IQR, 6-18%), and the percentage with CD4 gain < 15% was reduced from 85% at baseline to 11%. In those aged 60-156 months, median CD4 cell count gain was 275 cells/microl (IQR, 84-518 cells/microl), and the percentage with CD4 < 200 cells/mul reduced from 51% at baseline to 11%. Treatment outcomes included; 1012 (85%) alive and on ART, 36 (3%) deaths, 15 (1%) stopped ART, 89 (8%) lost to follow-up, and 31 (3%) with unknown outcomes. Overall probability of survival at 12 months was 0.87 (0.84-0.89). Side effects caused a change to alternative antiretroviral drugs in 26 (2%) but no deaths.
Very satisfactory early outcomes can be achieved in children in RLS using generic adult FDC antiretroviral tablets. These findings strongly favour their use as an "interim solution" for scaling-up ART in children; however, more appropriate pediatric antiretroviral drugs remain urgently needed.

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    • "First, specific medications, such as lopinavir/ritonavir (LPV/r) and abacavir (ABC), may be preferred in guidelines for clinical reasons [9-12], but their costs remain higher as well. Second, fixed-dose combinations (FDCs) are widely used in many ART programs and often lead to substantial cost-savings compared to their individual component drugs, as well as dosing convenience and improved adherence [13-15]. The production of pediatric FDCs has improved drastically over the past few years, resulting in several dual and triple dispersible formulations [7,16]. "
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    ABSTRACT: Background Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. Methods We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0–13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. Results The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. Conclusions The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments.
    Full-text · Article · May 2014 · BMC Health Services Research
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    • "As with most other paediatric HIV treatment programmes in resource-limited settings [38,39], we resorted to using adult, generic fixed-dose combination tablets cut in half or quartered. In the absence of pill-cutters this usually resulted in unequal-sized fractions and could have inadvertently contributed to inappropriate, particularly sub-therapeutic, drug doses particularly with the LPV/r gel capsules [40]. "
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    ABSTRACT: There is little data on responses to combination antiretroviral therapy (cART) among HIV-infected children in the West African region. We describe treatment outcomes among HIV-1 and HIV-2 infected children initiating cART in a research clinic in The Gambia, West Africa. All treatment naive HIV-infected children who initiated cART according to the WHO ART guidelines for children between October 2004 and December 2009 were included in the analysis. Kaplan-Meir estimates and sign-rank test were used to investigate the responses to treatment. 65 HIV-1 and five HIV-2 infected children aged < 15 years were initiated on cART over this time period. HIV-1 infected children were treated with a combination of Zidovudine or Stavudine + Lamivudine + Nevirapine or Efavirenz while children with HIV-2 were treated with Zidovudine + Lamivudine + ritonavir-boosted Lopinavir. HIV-1 infected children were followed-up for a median (IQR) duration of 20.1 months (6.9 - 34.3), with their median (IQR) age at treatment initiation, CD4% and plasma viral load at baseline found to be 4.9 years (2.1 - 9.1), 13.0% (7.0 - 16.0) and 5.4 log10 copies/ml (4.4 - 6.0) respectively. The median age at treatment initiation of the five HIV-2 infected children was 12 years (range: 4.6 - 14.0) while their median baseline CD4+ T cell count and HIV-2 viral load were 140 cells/mm3 (Range: 40 - 570 cells/mm3) and 4.5 log10copies/mL (Range: 3.1 - 4.9 log10copies/mL) respectively.Among HIV-1 infected children <5 years of age at ART initiation, the median (IQR) increases in CD4% from baseline to 12, 24 and 36 months were 14% (8 - 19; P = 0.0004), 21% (15 - 22; P = 0.005) and 15% (15 - 25; P = 0.0422) respectively, while the median (IQR) increase in absolute CD4 T cell count from baseline to 12, 24 and 36 months for those ≥5 years at ART initiation were 470 cells/mm3 (270 - 650; P = 0.0005), 230 cells/mm3 (30 - 610; P = 0.0196) and 615 cells/mm3 (250 - 1060; P = 0.0180) respectively. The proportions of children achieving undetectable HIV-1 viral load at 6-, 12-, 24- and 36 months of treatment were 24/38 (63.2%), 20/36 (55.6%), 8/22 (36.4%) and 7/12 (58.3%) respectively. The probability of survival among HIV-1 infected children after 12 months on ART was 89.9% (95% CI 78.8 - 95.3). CD4 T cell recovery was sub-optimal in all the HIV-2 infected children and none achieved virologic suppression. Two of the HIV-2 infected children died within 6 months of starting treatment while the remaining three were lost to follow-up. The beneficial effects of cART among HIV-1 infected children in our setting are sustained in the first 24 months of treatment with a significant improvement in survival experience up to 36 months; however the outcome was poor in the few HIV-2 infected children initiated on cART.
    Full-text · Article · Jul 2012 · BMC Pediatrics
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    • "Despite this, we observed overall high and sustained survival and retention rates in children treated with ART up to 2 years after therapy start. These findings are consistent with reports from other programs from resource-limited settings [10,25,37]. "
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    ABSTRACT: Children living with HIV continue to be in urgent need of combined antiretroviral therapy (ART). Strategies to scale up and improve pediatric HIV care in resource-poor regions, especially in sub-Saharan Africa, require further research from these settings. We describe treatment outcomes in children treated in rural Uganda after 1 and 2 years of ART start. Cross-sectional assessment of all children treated with ART for 12 (M12) and 24 (M24) months was performed. CD4 counts, HIV RNA levels, antiretroviral resistance patterns, and non-nucleoside reverse transcriptase inhibitor (NNRTI) plasma concentrations were determined. Patient adherence and antiretroviral-related toxicity were assessed. Cohort probabilities of retention in care were 0.86 at both M12 and M24. At survey, 71 (83%, M12) and 32 (78%, M24) children remained on therapy, and 84% participated in the survey. At ART start, 39 (45%) were female; median age was 5 years. Median initial CD4 percent was 11% [IQR 9-15] in children < 5 years old (n = 12); CD4 count was 151 cells/mm(3) [IQR 38-188] in those ≥ 5 years old (n = 26). At M12, median CD4 gains were 11% [IQR 10-14] in patients < 5 years old, and 206 cells/mm(3) [IQR 98-348] in ≥ 5 years old. At M24, median CD4 gains were 11% [IQR 5-17] and 132 cells/mm(3) [IQR 87-443], respectively. Viral suppression (< 400 copies/mL) was achieved in 59% (M12) and 33% (M24) of children. Antiretroviral resistance was found in 25% (M12) and 62% (M24) of children. Overall, 29% of patients had subtherapeutic NNRTI plasma concentrations. After one year of therapy, satisfactory survival and immunological responses were observed, but nearly 1 in 4 children developed viral resistance and/or subtherapeutic plasma antiretroviral drug levels. Regular weight-adjustment dosing and strategies to reinforce and maintain ART adherence are essential to maximize duration of first-line therapy in children in resource-limited countries.
    Full-text · Article · Jul 2011 · BMC Pediatrics
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