The contribution of family medicine to community-orientated health services in Mali: A short report.

Family medicine has not received appropriate attention in the sub-Saharan African context. In particular, family medicine is rarely recognised as a medical speciality and most African countries are silent on the role of family medicine in their health systems. There is, however, an emerging interest in developing family medicine as a key component of primary healthcare. Postgraduate training in family medicine is progressing and many countries have already established specific training programmes. In addition, there have been attempts to define the importance of family medicine, which, we expect, this short report contributes to. Interviews were conducted with physicians, partners and beneficiaries of two international development projects funded by the Canadian government. The one project supports training of health professionals and the other education of healthy women and girls in the community. The objective was to document the strengthening of primary healthcare through the creation and adaptation of a new family and community medicine postgraduate medical programme (which includes both family and community medicine) emphasising field training, immersion in local communities and interdisciplinary collaboration. This article underlines the importance of family medicine in Mali by documenting how what is now termed family and community medicine can promote community-orientated health services. To do so, we use the examples of initiatives and actions done through two international health development projects.

Accreditation of private midwifery and nursing schools in Mali: a local sustainable solution to increasing the supply of qualified health workers.

BACKGROUND: The World Health Organization's Global Strategy on Human Resources for Health (HRH) emphasizes the importance of dynamic and effective health worker regulation for achieving the health-related Sustainable Development Goals, with the establishment of education standards and quality assurance of education programs being critical. Governments in West Africa have struggled to address the problems within their higher education systems for health professionals, and it is now generally acknowledged that private institutions can play a crucial role in revitalizing the region's outdated universities. However, the rapid expansion of private schools raises concerns about the quality of education and adequacy of regulatory mechanisms. The USAID-funded Mali HRH Strengthening Activity, led by IntraHealth International, assisted Mali's Ministry of Health and Social Development to deliver targeted HRH interventions to improve the quality of education in private universities, better manage available health workers, and initiate a decentralized strategy for health worker recruitment and motivation. CASE PRESENTATION: In 2018, the HRH activity leveraged the West African Health Organization (WAHO)'s accreditation system to support 10 private nursing schools to introduce WAHO's regionally accepted, competency-based curriculum in reproductive, maternal, newborn, and child health. The project undertook a 10-step process to work alongside private nursing and midwifery schools to assess their current status against WAHO regional standards, implement action plans to address identified gaps, and support the institutions toward accreditation. As a result, eight schools in Mali are now accredited compared to only three at project inception. CONCLUSIONS: This case study underscores the importance of private school accreditation in Mali to improve the quality of health worker training through a standardized local curriculum. By supporting existing regulatory bodies that oversee accreditation, local capacity for initial accreditation of private nursing schools has been increased. Engaging universities in a partnership that shows the benefits of accreditation while maintaining a focus on the need to protect communities is critical to success. If the global community is to meet the WHO's predicted health worker shortfall, then private education providers will need to be part of the solution. Robust and engaging health worker education accreditation systems are an essential part of that future.

Growth in the first 5 years after antiretroviral therapy initiation among HIV-infected children in the IeDEA West African Pediatric Cohort.

OBJECTIVE: To describe growth evolution and its correlates in the first 5 years of antiretroviral therapy (ART) initiation among HIV-infected children followed up in West Africa. METHODS: All HIV-infected children younger than 10 years followed in the IeDEA pWADA cohort while initiating ART, with at least one anthropometric measurement within the first 5 years of treatment were included in the study. Growth was described according to the WHO child growth standards, using Weight-for-age Z-score (WAZ), Height-for-age Z-score (HAZ) and Weight-for-Height/BMI-for-age Z-score (WHZ/BAZ). Growth evolution and its correlates, measured at ART initiation, were modelled in individual linear mixed models for each anthropometric indicator, with a spline term added at the 12-, 24- and 9-month time point for WAZ, HAZ and WHZ/BAZ, respectively. RESULTS: Among the 4156 children selected (45% girls, median age at ART initiation 3.9 years [IQR interquartile range 1.9-6.6], and overall 68% malnourished at ART initiation), important gains were observed in the first 12, 24 and 9 months on ART for WAZ, HAZ and WHZ/BAZ, respectively. Correlates at ART initiation of a better growth evolution overtime were early age (<2 years of age), severe immunodeficiency for age, and severity of malnutrition. CONCLUSIONS: Growth evolution is particularly strong within the first 2 years on ART but slows down after this period. Weight and height gains help to recover from pre-ART growth deficiency but are insufficient for the most severely malnourished. The first year on ART could be the best period for nutritional interventions to optimize growth among HIV-infected children in the long-term.

OBJECTIF: Décrire l'évolution de la croissance et ses corrélats au cours des cinq premières années d'initiation du traitement antirétroviral (ART) chez les enfants infectés par le VIH, suivis en Afrique de l'Ouest. MÉTHODES: Tous les enfants infectés par le VIH âgés de moins de 10 ans suivis dans la cohorte IeDEA pWADA au début de l'ART, avec au moins une mesure anthropométrique au cours des cinq premières années de traitement, ont été inclus dans l'étude. La croissance a été décrite selon les normes de croissance de l'enfant de l'OMS, en utilisant le Z-score Poids pour l'âge (WAZ), le Z-score Taille pour l'âge (HAZ) et le Z-score Poids-pour-Taille/IMC pour l'âge (WHZ/BAZ). L'évolution de la croissance et ses corrélats, mesurés au début de l'ART, ont été modélisés dans des modèles mixtes linéaires individuels pour chaque indicateur anthropométrique, avec un terme spline ajouté aux points 12, 24 et 9 mois pour WAZ, HAZ et WHZ/BAZ respectivement. RÉSULTATS: Parmi les 4.156 enfants sélectionnés (45% de filles, âge médian au début l'ART 3,9 ans [intervalle interquartile IQR de 1,9 à 6,6] et au total 68% de malnutrition au début de l'ART), des gains importants ont été observés dans les 12, 24 et 9 premiers mois sous ART pour WAZ, HAZ et WHZ/BAZ respectivement. Les corrélats au début de l'ART pour une meilleure évolution de la croissance au cours du temps étaient: l'âge précoce (<2 ans), un déficit immunitaire sévère pour l'âge et la sévérité de la malnutrition. CONCLUSIONS: L'évolution de la croissance est particulièrement forte au cours des deux premières années sous ART, mais ralentit après cette période. Les gains de poids et de taille aident à récupérer du retard de croissance pré-ART mais sont insuffisants pour les plus sévèrement malnutris. La première année sous ART pourrait être la meilleure période pour les interventions nutritionnelles visant à optimiser la croissance à long terme des enfants infectés par le VIH.

Access to antiretroviral therapy in HIV-infected children aged 0-19 years in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium, 2004-2015: A prospective cohort study.

INTRODUCTION: Access to antiretroviral therapy (ART) is a global priority. However, the attrition across the continuum of care for HIV-infected children between their HIV diagnosis and ART initiation is not well known. We analyzed the time from enrollment into HIV care to ART initiation in HIV-infected children within the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium. METHODS AND FINDINGS: We included 135,479 HIV-1-infected children, aged 0-19 years and ART-naïve at enrollment, between 1 January 2004 and 31 December 2015, in IeDEA cohorts from Central Africa (3 countries; n = 4,948), East Africa (3 countries; n = 22,827), West Africa (7 countries; n = 7,372), Southern Africa (6 countries; n = 93,799), Asia-Pacific (6 countries; n = 4,045), and Latin America (7 countries; n = 2,488). Follow-up in these cohorts is typically every 3-6 months. We described time to ART initiation and missed opportunities (death or loss to follow-up [LTFU]: last clinical visit >6 months) since baseline (the date of HIV diagnosis or, if unavailable, date of enrollment). Cumulative incidence functions (CIFs) for and determinants of ART initiation were computed, with death and LTFU as competing risks. Among the 135,479 children included, 99,404 (73.4%) initiated ART, 1.9% died, 1.4% were transferred out, and 20.4% were lost to follow-up before ART initiation. The 24-month CIF for ART initiation was 68.2% (95% CI: 67.9%-68.4%); it was lower in sub-Saharan Africa-ranging from 49.8% (95% CI: 48.4%-51.2%) in Central Africa to 72.5% (95% CI: 71.5%-73.5%) in West Africa-compared to Latin America (71.0%, 95% CI: 69.1%-72.7%) and the Asia-Pacific (78.3%, 95% CI: 76.9%-79.6%). Adolescents aged 15-19 years and infants <1 year had the lowest cumulative incidence of ART initiation compared to other ages: 62.2% (95% CI: 61.6%-62.8%) and 66.4% (95% CI: 65.7%-67.0%), respectively. Overall, 49.1% were ART-eligible per local guidelines at baseline, of whom 80.6% initiated ART. The following children had lower cumulative incidence of ART initiation: female children (p < 0.01); those aged <1 year, 2-4 years, 5-9 years, and 15-19 years (versus those aged 10-14 years, p < 0.01); those who became eligible during follow-up (versus eligible at enrollment, p < 0.01); and those receiving care in low-income or lower-middle-income countries (p < 0.01). The main limitations of our study include left truncation and survivor bias, caused by deaths of children prior to enrollment, and use of enrollment date as a proxy for missing data on date of HIV diagnosis, which could have led to underestimation of the time between HIV diagnosis and ART initiation. CONCLUSIONS: In this study, 68% of HIV-infected children initiated ART by 24 months. However, there was a substantial risk of LTFU before ART initiation, which may also represent undocumented mortality. In 2015, many obstacles to ART initiation remained, with substantial inequities. More effective and targeted interventions to improve access are needed to reach the target of treating 90% of HIV-infected children with ART.

Treatment of retinoblastoma in Sub-Saharan Africa: Experience of the paediatric oncology unit at Gabriel Toure Teaching Hospital and the Institute of African Tropical Ophthalmology, Bamako, Mali.

BACKGROUND: Retinoblastoma (Rb) is the most common intraocular primary malignancy in children. In industrialised countries, the cure rate is about 95%. We present the results of a prospective study on the management of Rb in the paediatric oncology unit of Gabriel Touré Teaching Hospital and African Institute of Tropical Ophthalmology, from November 1, 2011 to December 31, 2015. PROCEDURE: The aims of this prospective study were to evaluate the treatment of localised Rb, ocular prosthesis after enucleation, conservative management for bilateral Rb as well as survival rates in all patients. Patients with early stage Rb at diagnosis were included. The treatment was performed according to the retinoblastoma treatment guidelines of the French-African Paediatric Oncology Group. RESULTS: Eighty-eight patients were included in the study. Sex ratio was 1:1 (M = 44, F = 44). Median age at diagnosis was 3 years (range: 2 months-5 years). Unilateral intraocular Rb was predominant (n = 50; 56.8%). Conservative treatments were performed on nine eyes in nine patients. Overall survival and event-free survival of the entire cohort at the end of 4 years were 73% (95% CI 60.8-81.2%) and 59% (95% CI 47.9-69.5%), respectively, with a median follow-up of 3.7 years (0.1-5.6 years). In conclusion, early enucleation in early stage of Rb can improve outcomes in resource-limited countries. Delayed enucleation and refusal of adherence to treatment are still major concerns and remain a barrier to improving overall patient survival.

Evaluation of a Nutritional Support Intervention in Malnourished HIV-Infected Children in Bamako, Mali.

BACKGROUND: We assessed a nutritional support intervention in malnourished HIV-infected children in a HIV-care program of the University Hospital Gabriel Touré, Bamako, Mali. METHODS: All HIV-infected children younger than 15 years were diagnosed for malnutrition between 07 and 12, 2014. Malnutrition was defined according to the WHO growth standards with Z-scores. Two types were studied: acute malnutrition (AM) and chronic malnutrition (CM). All participants were enrolled in a 6-month prospective interventional cohort, receiving Ready-To-Use Therapeutic Food, according to type of malnutrition. The nutritional intervention was offered until child growth reached -1.5 SD threshold. Six-month probability to catch up growth (>-2 SD) was assessed for AM using Kaplan-Meier curves and Cox model. RESULTS: Among the 348 children screened, 198 (57%) were malnourished of whom 158 (80%) children were included: 97 (61%) for AM (35 with associated CM) and 61 (39%) with CM. Fifty-nine percent were boys, 97% were on antiretroviral therapy, median age was 9.5 years (Interquartile Range: 6.7-12.3). Among children with AM, 74% catch-up their growth at 6-month; probability to catch-up growth was greater for those without associated CM (adjusted Hazard Ratio = 1.97, CI 95%: 1.13 to 3.44). Anemia decreased significantly from 40% to 12% at the end of intervention (P < 0.001). CONCLUSIONS: This macronutrient intervention showed 6-month benefits for weight gain and reduced anemia among these children mainly on antiretroviral therapy for years and aged greater than 5 years at inclusion. Associated CM slows down AM recovery and needs longer support. Integration of nutritional screening and care in the pediatric HIV-care package is needed to optimize growth and prevent metabolic disorders.

Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation.

BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric IeDEA clinical centres in five West-African countries. We estimated the incidence of switch (at least one a drug class change) within 24 months of ART and associated factors were identified in a multinomial logistic regression. Among children with clinical-immunological failure, we estimated the 24-month probability of switching to a second-line and associated factors, using competing risks. Children who switched to second-line ART following the withdrawal of nelfinavir in 2007 were excluded. RESULTS: Overall, 2820 children initiated ART at a median age of 5 years; 144 (5%) were on nelfinavir. At 24-month post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months. Of these children, 21 (7%) switched to second-line after a median time of 21 weeks in failure. This was associated with older age [subdistribution hazard ratio (sHR) 1.21, 95% confidence interval (95% CI) 1.10-1.33] and longer time on ART (sHR 1.16, 95% CI 1.07-1.25). CONCLUSION: Switches for clinical failure were rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes.

Effect of Age at Antiretroviral Therapy Initiation on Catch-up Growth Within the First 24 Months Among HIV-infected Children in the IeDEA West African Pediatric Cohort.

BACKGROUND: We described malnutrition and the effect of age at antiretroviral therapy (ART) initiation on catch-up growth over 24 months among HIV-infected children enrolled in the International epidemiologic Databases to Evaluate Aids West African paediatric cohort. METHODS: Malnutrition was defined at ART initiation (baseline) by a Z score <-2 standard deviations, according to 3 anthropometric indicators: weight-for-age (WAZ) for underweight, height-for-age (HAZ) for stunting and weight-for-height/BMI-for-age (WHZ/BAZ) for wasting. Kaplan-Meier estimates for catch-up growth (Z score ≥-2 standard deviations) on ART, adjusted for gender, immunodeficiency and malnutrition at ART initiation, ART regimen, time period and country, were compared by age at ART initiation. Cox proportional hazards regression models determined predictors of catch-up growth on ART over 24 months. RESULTS: Between 2001 and 2012, 2004 HIV-infected children <10 years of age were included. At ART initiation, 51% were underweight, 48% were stunted and 33% were wasted. The 24-month adjusted estimates for catch-up growth were 69% [95% confidence interval (CI): 57-80], 61% (95% CI: 47-70) and 90% (95% CI: 76-95) for WAZ, HAZ and WHZ/BAZ, respectively. Adjusted catch-up growth was more likely for children <5 years of age at ART initiation compared with children ≥5 years for WAZ, HAZ (P < 0.001) and WHZ/BAZ (P = 0.026). CONCLUSIONS: Malnutrition among these children is an additional burden that has to be urgently managed. Despite a significant growth improvement after 24 months on ART, especially in children <5 years, a substantial proportion of children still never achieved catch-up growth. Nutritional care should be part of the global healthcare of HIV-infected children in sub-Saharan Africa.

Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.

BACKGROUND: The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries. METHODS: We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year. RESULTS: A total of 34,706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. CONCLUSIONS: Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.

L'epilepsie en milieu scolaire : enquete chez les enseignants de la ville de Kati au Mali et revue de la litterature

Introduction La prevalence de l'epilepsie en Afrique subsaharienne est elevee. Nous avons mene une etude transversale et descriptive dans l'ensemble des ecoles primaires de la ville de Kati (200 000 habitants). Les enseignants furent interviewes de maniere exhaustive a l'aide de questionnaires portant; d'une part; sur les connaissances; attitudes et pratiques des enseignants en matiere d'epilepsie et; d'autre part; sur leurs avis sur les consequences psychologiques; sociales pour l'enfant epileptique et les incidences sur sa scolarite.Resultats Nous avons interroge 92 enseignants (60 hommes et 32 femmes). L'age moyen des enseignants etait de 30 ans. La majorite d'entre eux avait une experience professionnelle de plus de 5 ans. Environ 38% des enseignants attribuaient la maladie a une cause surnaturelle. Plus de 39% des enseignants pensaient que l'epilepsie etait contagieuse et 61% pensaient que l'epilepsie etait incurable. 79% interdisaient systematiquement la pratique du sport a l'enfant epileptique. Environ 55% pensaient que l'enfant epileptique avait des capacites cognitives inferieures a celles de l'enfant non epileptique et 88% affirmaient que l'enfant epileptique etait incapable d'avoir une scolarite normale. 59% trouvaient que l'eleve epileptique etait victime de stigmatisation et de marginalisation. Devant une crise; 68% renvoyaient l'enfant au domicile.Conclusion Ce travail fait apparaitre un besoin de formation des enseignants en matiere d'epilepsie. Les donnees actuelles sur la frequence de l'epilepsie en milieu scolaire justifient une attention particuliere des services de sante et de ceux de l'education nationale sur la scolarisation de l'enfant epileptique

Antiretroviral treatment response of HIV-infected children after prevention of mother-to-child transmission in West Africa.

INTRODUCTION: We assessed the rate of treatment failure of HIV-infected children after 12 months on antiretroviral treatment (ART) in the Paediatric IeDEA West African Collaboration according to their perinatal exposure to antiretroviral drugs for preventing mother-to-child transmission (PMTCT). METHODS: A retrospective cohort study in children younger than five years at ART initiation between 2004 and 2009 was nested within the pWADA cohort, in Bamako-Mali and Abidjan-Côte d'Ivoire. Data on PMTCT exposure were collected through a direct review of children's medical records. The 12-month Kaplan-Meier survival without treatment failure (clinical or immunological) was estimated and their baseline factors studied using a Cox model analysis. Clinical failure was defined as the appearance or reappearance of WHO clinical stage 3 or 4 events or any death occurring within the first 12 months of ART. Immunological failure was defined according to the 2006 World Health Organization age-related immunological thresholds for severe immunodeficiency. RESULTS: Among the 1035 eligible children, PMTCT exposure was only documented for 353 children (34.1%) and remained unknown for 682 (65.9%). Among children with a documented PMTCT exposure, 73 (20.7%) were PMTCT exposed, of whom 61.0% were initiated on a protease inhibitor-based regimen, and 280 (79.3%) were PMTCT unexposed. At 12 months on ART, the survival without treatment failure was 40.6% in the PMTCT-exposed group, 25.2% in the unexposed group and 18.5% in the children with unknown exposure status (p=0.002). In univariate analysis, treatment failure was significantly higher in children unexposed (HR 1.4; 95% CI: 1.0-1.9) and with unknown PMTCT exposure (HR 1.5; 95% CI: 1.2-2.1) rather than children PMTCT-exposed (p=0.01). In the adjusted analysis, treatment failure was not significantly associated with PMTCT exposure (p=0.15) but was associated with immunodeficiency (aHR 1.6; 95% CI: 1.4-1.9; p=0.001), AIDS clinical events (aHR 1.4; 95% CI: 1.0-1.9; p=0.02) at ART initiation and receiving care in Mali compared to Côte d'Ivoire (aHR 1.2; 95% CI: 1.0-1.4; p=0.04). CONCLUSIONS: Despite a low data quality, PMTCT-exposed West African children did not have a poorer 12-month response to ART than others. Immunodeficiency and AIDS events at ART initiation remain the main predictors associated with treatment failure in this operational context.

Association between age at antiretroviral therapy initiation and 24-month immune response in West-African HIV-infected children.

OBJECTIVE: We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4 cell response in West African HIV-infected children. METHODS: All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4 cell count measurements, including one at ART initiation (baseline) were included. CD4 cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4 cell count, sex, first-line ART regimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model compared immune recovery for age within 24 months post-ART. RESULTS: Of the 4808 children initiated on ART, 3014 were enrolled at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4 cell gains compared with children less than 2 years, the reference group (P<0.001). However, by 24 months, we observed higher CD4 cell gain in children who initiated ART between 3 and 4 years compared with those less than 2 years (P<0.001). The 24-month CD4 cell gain was also strongest in immunodeficient children at baseline. Among these children, 75% reached immune recovery: 12-month rates were significantly highest in all those aged 2-5 years at ART initiation compared with those less than 2 years. Beyond 12 months on ART, immune recovery was significantly lower in children initiated more than 5 years (adjusted hazard ratio: 0.69, 95% confidence interval: 0.56-0.86). CONCLUSION: These results suggest that both the initiation of ART at the earliest age less than 5 years and before any severe immunodeficiency is needed for improving 24-month immune recovery on ART.

Reasons for hospitalization in HIV-infected children in West Africa.

INTRODUCTION: Current knowledge on morbidity and mortality in HIV-infected children comes from data collected in specific research programmes, which may offer a different standard of care compared to routine care. We described hospitalization data within a large observational cohort of HIV-infected children in West Africa (IeDEA West Africa collaboration). METHODS: We performed a six-month prospective multicentre survey from April to October 2010 in five HIV-specialized paediatric hospital wards in Ouagadougou, Accra, Cotonou, Dakar and Bamako. Baseline and follow-up data during hospitalization were recorded using a standardized clinical form, and extracted from hospitalization files and local databases. Event validation committees reviewed diagnoses within each centre. HIV-related events were defined according to the WHO definitions. RESULTS: From April to October 2010, 155 HIV-infected children were hospitalized; median age was 3 years [1-8]. Among them, 90 (58%) were confirmed for HIV infection during their stay; 138 (89%) were already receiving cotrimoxazole prophylaxis and 64 children (40%) had initiated antiretroviral therapy (ART). The median length of stay was 13 days (IQR: 7-23); 25 children (16%) died during hospitalization and four (3%) were transferred out. The leading causes of hospitalization were WHO stage 3 opportunistic infections (37%), non-AIDS-defining events (28%), cachexia and other WHO stage 4 events (25%). CONCLUSIONS: Overall, most causes of hospitalizations were HIV related but one hospitalization in three was caused by a non-AIDS-defining event, mostly in children on ART. HIV-related fatality is also high despite the scaling-up of access to ART in resource-limited settings.

Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS.

INTRODUCTION: There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. METHODS: Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥ 18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7 g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. RESULTS: As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was-2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p ≤ 0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ≥ 1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p ≤ 0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤-3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01). CONCLUSIONS: Severe anaemia is frequent at baseline and guides the first-line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care.

Outcomes of antiretroviral therapy in children in Asia and Africa: a comparative analysis of the IeDEA pediatric multiregional collaboration.

BACKGROUND: We investigated 18-month incidence and determinants of death and loss to follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. METHODS: HIV-infected children (positive polymerase chain reaction <18 months or positive serology ≥18 months) from International Epidemiologic Databases to Evaluate AIDS cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of 2 failure types: death and loss to follow-up (>6 months). FINDINGS: Data on 13,611 children, from Asia (N = 1454), East Africa (N = 3114), Southern Africa (N = 6212), and West Africa (N = 2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East Africa, 5.4% in Asia, 5.7% in Southern Africa, and 7.4% in West Africa (P = 0.01). Age < 24 months, World Health Organization stage 4, CD4 < 10%, attending a private sector clinic, larger cohort size, and living in West Africa were independently associated with poorer survival. The adjusted risk of loss to follow-up was 4.1% in Asia, 9.0% in Southern Africa, 14.0% in East Africa, and 21.8% in West Africa (P < 0.01). Age < 12 months, nonnucleoside reverse transcriptase inhibitor I-based ART regimen, World Health Organization stage 4 at ART start, ART initiation after 2005, attending a public sector or a nonurban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East Africa or West Africa were significantly associated with higher loss to follow-up. CONCLUSIONS: Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at the program level.

HIV status disclosure and retention in care in HIV-infected adolescents on antiretroviral therapy (ART) in West Africa.

OBJECTIVE: We assessed the effect of HIV status disclosure on retention in care from initiation of antiretroviral therapy (ART) among HIV-infected children aged 10 years or more in Cote d'Ivoire, Mali and Sénégal. METHODS: Multi-centre cohort study within five paediatric clinics participating in the IeDEA West Africa collaboration. HIV-infected patients were included in this study if they met the following inclusion criteria: aged 10-21 years while on ART; having initiated ART ≥ 200 days before the closure date of the clinic database; followed ≥ 15 days from ART initiation in clinics with ≥ 10 adolescents enrolled. Routine follow-up data were merged with those collected through a standardized ad hoc questionnaire on awareness of HIV status. Probability of retention (no death or loss-to-follow-up) was estimated with Kaplan-Meier method. Cox proportional hazard model with date of ART initiation as origin and a delayed entry at date of 10th birthday was used to identify factors associated with death or loss-to-follow-up. RESULTS: 650 adolescents were available for this analysis. Characteristics at ART initiation were: median age of 10.4 years; median CD4 count of 224 cells/mm³ (47% with severe immunosuppression), 48% CDC stage C/WHO stage 3/4. The median follow-up on ART after the age of 10 was 23.3 months; 187 adolescents (28.8%) knew their HIV status. The overall probability of retention at 36 months after ART initiation was 74.6% (95% confidence interval [CI]: 70.5-79.0) and was higher for those disclosed compared to those not: adjusted hazard ratio for the risk of being death or loss-to-follow-up = 0.23 (95% CI: 0.13-0.39). CONCLUSION: About 2/3 of HIV-infected adolescents on ART were not aware of their HIV status in these ART clinics in West Africa but disclosed HIV status improved retention in care. The disclosure process should be thus systematically encouraged and organized in adolescent populations.

12-month mortality and loss-to-program in antiretroviral-treated children: The IeDEA pediatric West African Database to evaluate AIDS (pWADA), 2000-2008.

BACKGROUND: The IeDEA West Africa Pediatric Working Group (pWADA) was established in January 2007 to study the care and treatment of HIV-infected children in this region. We describe here the characteristics at antiretroviral treatment (ART) initiation and study the 12-month mortality and loss-to-program of HIV-infected children followed in ART programs in West Africa. METHODS: Standardized data from HIV-infected children followed-up in ART programs were included. Nine clinical centers from six countries contributed to the dataset (Benin, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal). Inclusion criteria were the followings: age 0-15 years and initiated triple antiretroviral drug regimens. Baseline time was the date of ART initiation. WHO criteria was used to define severe immunosuppression based on CD4 count by age or CD4 percent < 15%. We estimated the 12-month Kaplan-Meier probabilities of mortality and loss-to-program (death or loss to follow-up > 6 months) after ART initiation and factors associated with these two outcomes. RESULTS: Between June 2000 and December 2007, 2170 children were included. Characteristics at ART initiation were the following: median age of 5 years (Interquartile range (IQR: 2-9) and median CD4 percentage of 13% (IQR: 7-19). The most frequent drug regimen consisted of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitors (62%). During the first 12 months, 169 (7.8%) children died and 461(21.2%) were lost-to-program. Overall, in HIV-infected children on ART, the 12-month probability of death was 8.3% (95% Confidence Interval (CI): 7.2-9.6%), and of loss-to-program was 23.1% (95% CI: 21.3-25.0%). Both mortality and loss-to program were associated with advanced clinical stage, CD4 percentage < 15% at ART initiation and year (> 2005) of ART initiation. CONCLUSION: Innovative and sustainable approaches are needed to better document causes of death and increase retention in HIV pediatric clinics in West Africa.

Level of viral load and antiretroviral resistance after 6 months of non-nucleoside reverse transcriptase inhibitor first-line treatment in HIV-1-infected children in Mali.

OBJECTIVES: To evaluate the virological response and to describe the resistance profiles in the case of failure after 6 months of first-line highly active antiretroviral therapy (HAART) in HIV-1-infected children living in resource-limited settings. PATIENTS AND METHODS: Ninety-seven HIV-1-infected children who started two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (mainly zidovudine/lamivudine/nevirapine) in Mali were prospectively studied. Virological failure (VF) was defined as loss to follow-up, death or HIV-1 RNA viral load (VL) of >400 copies/mL at 6 months. When VL was >50 copies/mL, a genotypic resistance test was performed. RESULTS: Among the 97 children, median age at antiretroviral initiation was 31 months and the majority were in WHO clinical (77.3%) and immunological (70.1%) stage III or IV. At month 6, 44% of children had VL > 400 copies/mL (61% VF). Among the children with detectable VL, 30/37 genotypic resistance tests were available, 8 with wild-type viruses and 22 with resistance mutations (73%): 19 M184V/I, 21 NNRTI mutations and only 3 thymidine analogue mutations (TAMs) (K70R, D67N and L210W in three distinct viruses). At failure, 6/8 children with wild-type viruses had a VL of <1000 copies/mL whereas 21/22 with resistant viruses had a VL of >1000 copies/mL. CONCLUSIONS: Under NNRTI-based regimens, early detection of VF could allow the reinforcement of adherence when VL was <1000 copies/mL, because in most of these cases no resistance mutations were detected, or a change to a protease inhibitor-based regimen if VL was >1000 copies/mL. The low frequency of TAMs suggests that most NRTIs can be used in a second-line regimen after early failure.