Disparities in access to Dolutegravir in West African children, adolescents and young adults aged 0-24 years living with HIV. A IeDEA Pediatric West African cohort analysis.

Introduction: We describe the 24-month incidence of Dolutegravir (DTG)-containing antiretroviral treatment (ART) initiation since its introduction in 2019 in the pediatric West African IeDEA cohorts. Methods: We included all patients aged 0-24 years on ART, from nine clinics in Côte d'Ivoire (n=4), Ghana, Nigeria, Mali, Benin, and Burkina Faso. Baseline varied by clinic and was defined as date of first DTG prescription; patients were followed-up until database closure/death/loss to follow-up (LTFU, no visit ≥ 7 months), whichever came first. We computed the cumulative incidence function for DTG initiation; associated factors were explored in a shared frailty model, accounting for clinic heterogeneity. Results: Since 2019, 3,350 patients were included; 49% were female;79% had been on ART ≥ 12 months. Median baseline age was 12.9 years (IQR: 9-17). Median follow-up was 14 months (IQR: 7-22). The overall cumulative incidence of DTG initiation reached 35.5% (95% CI: 33.7-37.2) and 56.4% (95% CI: 54.4-58.4) at 12 and 24 months, respectively. In univariate analyses, those aged <5 years and females were overall less likely to switch. Adjusted on ART line and available viral load (VL) at baseline, females >10 years were less likely to initiate DTG compared to males of the same age (aHR among 10-14 years: 0.62, 95% CI: 0.54-0.72; among ≥15 years: 0.43, 95% CI: 0.36-0.50), as were those with detectable VL (> 50 copies/mL) compared to those in viral suppression (aHR: 0.86, 95% CI: 0.77-0.97) and those on PIs compared to those on NNRTIs (aHR after 12 months of roll-out: 0.75, 95% CI: 0.65-0.86). Conclusion: Access to paediatric DTG was incomplete and unequitable in West African settings: children <5years, females ≥ 10 years and those with detectable viral load were least likely to access DTG. Maintained monitoring and support of treatment practices is required to better ensure universal and equal access. Key messages: What is already known on this topic?: Dolutegravir (DTG)-based ART regimens are recommended as the preferred first-line ART regimens recommended by the World Health Organisation in all people living with HIV since 2018, with a note of caution for pregnant women, then confirmed in all children with approved DTG dosing and adolescents since 2019.Deployment of universal DTG access in adults in West Africa has faced challenges such as infrastructure challenges, and healthcare system disparities, and was hindered by initial perinatal safety concerns affecting greatly women of childbearing age.Specific data on access to DTG in children, adolescents and young adults in West Africa is limited.What this study adds ?: This study describes the dynamic of the DTG roll-out over the first 24 months and its correlates since 2019 in a large West African multicentric cohort of children, adolescents and youth.We observed a rapid scale-up of DTG among children, adolescents and young adults living with HIV in West Africa, despite the COVID-19 pandemic.However, DTG access after 24 months was incomplete and unequitable, with adolescent girls and young women being less likely to initiate DTG compared to males, as were those with a detectable viral load (> 50 copies/mL) compared to those in success.Younger children < 5 years were also less likely to initiate DTG, explained by the later approval of paediatric formulations and their low availability.How this study might affect research, practice or policy?: Maintained monitoring, training and updating guidance for healthcare workers is essential to ensure universal access to DTG, especially for females, for whom inequity begins age 10 years.Efforts to improve access to universal DTG in West Africa require multifaceted interventions including healthcare infrastructure improvement and facilitation of paediatric antiretroviral forecasting and planification.

Determination of reverse transcriptase inhibitor resistance mutations in HIV-1 infected children in Côte d'Ivoire.

Treatment scale-up is leading to a progressive increase in HIV resistance to antiretrovirals, especially in children. To assess resistance to reverse transcriptase inhibitors (RTIs) in HIV-1 infected children in Côte d'Ivoire, genotypic resistance tests were performed and interpreted using the ANRS algorithm (www.hivfrenchresistance.org). Phylogenetic trees were created using BioEdit v7 and Mega7 software. The frequency of resistance to at least one RTI was 79%. It was 88% for nucleoside reverse transcriptase inhibitors (NRTIs), 71% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 63% for both classes (NRTI + NNRTI). The frequency of resistance was 50% for the ZDV + 3TC + EFV combination, 42% for the ABC + 3TC + EFV combination, and 8% for the TDF + 3TC + EFV combination. Frequently encountered resistance mutations were for NRTIs: M184V (88%), TAMs (67%), T215F/I/V/Y (33%), and L74I/V (24%); for NNRTIs: K103N/S (74%), P225H (26%), and G190A/E/Q (24%). The synthesis of phylogenetic analyses showed the predominance of the viral subtype CRF02_AG (85%). These results show a high prevalence of resistance to RTIs in children infected with HIV-1. Hence the interest of a more accessible monitoring of viral load and genotypic resistance tests in HIV-1 infected children undergoing treatment in Côte d'Ivoire.

Models of support for disclosure of HIV status to HIV-infected children and adolescents in resource-limited settings.

INTRODUCTION: Disclosure of HIV status to HIV-infected children and adolescents is a major care challenge. We describe current site characteristics related to disclosure of HIV status in resource-limited paediatric HIV care settings within the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS: An online site assessment survey was conducted across the paediatric HIV care sites within six global regions of IeDEA. A standardized questionnaire was administered to the sites through the REDCap platform. RESULTS: From June 2014 to March 2015, all 180 sites of the IeDEA consortium in 31 countries completed the online survey: 57% were urban, 43% were health centres and 86% were integrated clinics (serving both adults and children). Almost all the sites (98%) reported offering disclosure counselling services. Disclosure counselling was most often provided by counsellors (87% of sites), but also by nurses (77%), physicians (74%), social workers (68%), or other clinicians (65%). It was offered to both caregivers and children in 92% of 177 sites with disclosure counselling. Disclosure resources and procedures varied across geographical regions. Most sites in each region reported performing staff members' training on disclosure (72% to 96% of sites per region), routinely collecting HIV disclosure status (50% to 91%) and involving caregivers in the disclosure process (71% to 100%). A disclosure protocol was available in 14% to 71% of sites. Among the 143 sites (79%) routinely collecting disclosure status process, the main collection method was by asking the caregiver or child (85%) about the child's knowledge of his/her HIV status. Frequency of disclosure status assessment was every three months in 63% of the sites, and 71% stored disclosure status data electronically. CONCLUSION: The majority of the sites reported offering disclosure counselling services, but educational and social support resources and capacities for data collection varied across regions. Paediatric HIV care sites worldwide still need specific staff members' training on disclosure, development and implementation of guidelines for HIV disclosure, and standardized data collection on this key issue to ensure the long-term health and wellbeing of HIV-infected youth.

High prevalence of dental caries among HIV-infected children in West Africa compared to uninfected siblings.

INTRODUCTION: The objectives of this study were to investigate the association between HIV infection and dental caries among children in West Africa, and to identify factors associated with dental caries among HIV-infected children. METHODS: We conducted a multi-center cross-sectional study in Mali, Senegal and Côte d'Ivoire with a random sample of HIV-infected children aged 5-15 years on antiretroviral therapy and their uninfected siblings. A standardized examination was performed by calibrated dentists. The association between the number of decayed, missing or filled permanent and primary teeth surfaces (DMFdefS) and HIV status was investigated by fitting multivariable zero-inflated negative binomial models, for each age group (<12 and ≥12 years). Factors associated with dental caries could be investigated only for HIV-infected children <12 years old. RESULTS: The sample included 420 HIV-infected children and 418 non-infected siblings. The median DMFdefS was 7 for the HIV-infected children and 2 for the uninfected siblings. The proportion of children with DMFdefS ≥1 was significantly higher among the HIV-infected children than uninfected children (86.0 percent versus 64.4 percent, P < 0.001). The HIV-infected children were less likely to be caries-free than the uninfected siblings in both age groups. We found a higher degree of caries experience among HIV-infected children < 12 years old, in whom it was associated with sweet drink consumption, history of night bottle use, immunosuppression, and younger age at study entry. CONCLUSIONS: Although preventable, the burden of dental disease was high in children from families affected by HIV in West Africa and was associated with HIV infection and immunosuppression.

Pregnancy incidence and associated factors among HIV-infected female adolescents in HIV care in urban Côte d'Ivoire, 2009-2013.

OBJECTIVE: Adolescents living with HIV are sexually active and engaged in risky sexual behaviors. Knowledge on how and to what extent adolescents in HIV care are affected by pregnancy is needed so as to adopt better preventive services. We estimated 4-year pregnancy incidence and correlates among HIV-infected female adolescents in HIV care in urban Côte d'Ivoire. DESIGN: We conducted retrospective analysis of a pediatric prospective cohort of the International epidemiological Databases to Evaluate AIDS (IeDEA) West Africa Collaboration. Female patients with confirmed HIV infection aged 10-19 years, having at least one clinical visit in 2009 to health facilities participating in the pediatric IeDEA West African cohort in Abidjan, Côte d'Ivoire, were included. Data on incident pregnancies were obtained through medical records and interviews with health professionals. Pregnancy incidence rate was estimated per 100 person-years (PY). Poisson regression models were used to identify factors associated with the first pregnancy and provided incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: In 2009, 266 female adolescents were included, with a median age of 12.8 years (interquartile range, IQR: 10.0-15.0), CD4 cell counts of 506 cells/mm(3) (IQR: 302-737), and 80% on antiretroviral treatment. At the 48th month, 17 new pregnancies were reported after 938 PY of follow-up: 13 girls had one pregnancy while 2 had two pregnancies. Overall incidence rate of pregnancy was 1.8/100 PY (95% CI: 1.1-2.9). High incidence was observed among those aged 15-19 years: 3.6/100 PY (95% CI: 2.2-5.9). Role of maternal death in the risk of pregnancy was at the limit of statistical significance (adjusted IRR: 3.1, 95% CI: 0.9-11.0; ref. non-maternal orphans). CONCLUSIONS: Incidence of pregnancy among HIV-infected adolescents in care aged 15-19 years reached a level observed in adult cohorts in Sub-Saharan Africa. Health personnel in pediatric care have to intensify their efforts to provide more realistic and age-adapted reproductive health services to meet the needs of adolescent patients already confronting issues of sexuality. Vulnerability of maternal orphans merits further investigation.

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.

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.

Oral lesions among HIV-infected children on antiretroviral treatment in West Africa.

OBJECTIVE: To estimate the prevalence of oral mucosal diseases and dental caries among HIV-infected children receiving antiretroviral treatment (ART) in West Africa and to identify the factors associated with the prevalence of oral mucosal lesions. METHODS: Multicentre cross-sectional survey in five paediatric HIV clinics in Côte d'Ivoire, Mali and Sénégal. A standardised examination was performed by trained dentists on a random sample of HIV-infected children aged 5-15 years receiving ART. The prevalence of oral and dental lesions and mean number of decayed, missing/extracted and filled teeth (DMFdefT) in temporary and permanent dentition were estimated with their 95% confidence interval (95% CI). We used logistic regression to explore the association between children's characteristics and the prevalence of oral mucosal lesions, expressed as prevalence odds ratio (POR). RESULTS: The median age of the 420 children (47% females) enrolled was 10.4 years [interquartile range (IQR) = 8.3-12.6]. The median duration on ART was 4.6 years (IQR = 2.6-6.2); 84 (20.0%) had CD4 count<350 cells/mm(3). A total of 35 children (8.3%; 95% CI: 6.1-11.1) exhibited 42 oral mucosal lesions (24 were candidiasis); 86.0% (95% CI = 82.6-89.3) of children had DMFdefT ≥ 1. The presence of oral mucosal lesions was independently associated with CD4 count < 350 cells/mm(3) (POR = 2.96, 95% CI = 1.06-4.36) and poor oral hygiene (POR = 2.69, 95% CI = 1.07-6.76). CONCLUSIONS: Oral mucosal lesions still occur in HIV-infected African children despite ART, but rarely. However, dental caries were common and severe in this population, reflecting the need to include oral health in the comprehensive care of HIV.

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.

Characterization of nevirapine (NVP) resistance mutations and HIV type 1 subtype in women from Abidjan (Côte d'Ivoire) after NVP single-dose prophylaxis of HIV type 1 mother-to-child transmission.

Nevirapine (NVP) single dose is widely used in developing countries to prevent HIV-1 mother-to-child transmission. However, this regimen selects key drug resistance mutations that can impair further HAART efficacy. We studied the HIV-1 reverse transcriptase genotype from 29 Ivoirian women 1 month after an NVP single-dose prophylaxis. NVP resistance mutations were observed in six (20.7%) women. The majority of the isolates were CRF02_AG. These results confirm previous studies and suggest the need for different prophylaxis regimens in this setting.