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 IeDEA West African paediatric cohort (pWADA). Methods Malnutrition was defined at ART initiation (baseline) by a Z-score <-2 SD, according to three 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 SD) 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 to children ≥5 years for WAZ, HAZ (P<0.001), and for 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.

No abstract

Background There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modelling analysis in children aged 1–5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups and regions. Methods ART-naïve children of age 12–59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation. Results About one quarter of the 5826 included children was from West Africa (24.6%). The median (first; third quartile) CD4% at the first visit was 16% (11%;23%), the median weight-for-age z-scores and height-for-age z-scores were −1.5 (−2.7; −0.6) and −2.5 (−3.5; −1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count<750 cells/mm3 or CD4%<25% was 0.2% (95%CI: −0.2%;0.3%), and the difference in the mean height-for-age z-scores of those who survived was −0.02 (95%CI: −0.04;0.01). Younger children aged 1–2 and children in West Africa had worse outcomes. Conclusions Our results demonstrate that earlier treatment initiation yields overall better growth and mortality outcomes, though we could not show any differences in outcomes between immediate ART and delaying until CD4 count/% falls below750/25%.

No abstract

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.

Introduction: Lopinavir/ritonavir-based antiretroviral therapy (ART) is recommended for all HIV-infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12-month response to lopinavir/ritonavir-based antiretroviral therapy in a cohort of West African children treated before the age of two years.Methods: HIV-1-infected, ART-naive except for a prevention of mother-to-child transmission (PMTCT), tuberculosis-free, and less than two years of age children with parent’s consent were enrolled in a 12-month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed.Results: Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8–18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost-to-follow-up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed-up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09–6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03–7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05–6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation.Conclusions: Twelve-month VS rate on lopinavir/ritonavir-based ART was high, comparable to those in Africa or high-income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy-to-identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.

BackgroundThe 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years.MethodsThe MONOD ANRS 12026 study is a phase 3 non-inferiority open-label randomised clinical trial conducted in Abidjan, Côte d’Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 12–15 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test).ResultsBetween May 2011 and January 2013, 156 children (median age 13.7 months) were initiated on ART. After 12–15 months on ART, 106 (68%) were randomised to one of the two treatment arms (54 LPV, 52 EFV); 97 (91%) were aged <3 years. At 12 months post-randomisation, 46 children (85.2%) from LPV versus 43 (82.7%) from EFV showed virological suppression (defined as a VL <500 copies/mL; difference, 2.5%; 95% confidence interval (CI), −11.5 to 16.5), whereas seven (13%) in LPV and seven (13.5%) in EFV were classed as having virological failure (secondary outcome, defined as a VL ≥1000 copies/mL; difference, 0.5%; 95% CI, −13.4 to 12.4). No significant differences in adverse events were observed, with two adverse events in LPV (3.7%) versus four (7.7%) in EFV (p = 0.43). On genotyping, 13 out of 14 children with virological failure (six out of seven EFV, seven out of seven LPV) had a drug-resistance mutation: nine (five out of six EFV, four out of seven LPV) had one or more major NNRTI-resistance mutations whereas none had an LPV/r-resistance mutation.ConclusionsAt the VL threshold of 500 copies/mL, we could not conclusively demonstrate the non-inferiority of EFV on viral suppression compared to LPV because of low statistical power. However, non-inferiority was confirmed for a VL threshold of <1000 copies/mL. Resistance analyses highlighted a high frequency of NNRTI-resistance mutations. A switch to an EFV-based regimen as a simplification strategy around ...

IntroductionThe World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso.MethodsAll children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion.ResultsAmong the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father's refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency.ConclusionsFear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.