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BackgroundCervical cancer prevention strategies recommend human papilloma virus (HPV) vaccination for female adolescents prior to their sexual debut. While HIV is a major risk factor for HPV infection in women of childbearing age, its prevalence among HIV-infected adolescent female is mostly unknown. This study aimed to describe the HPV prevalence and correlates among perinatally HIV-infected adolescent females prior to HPV immunisation.MethodsA cross-sectional survey was conducted from January to June 2016, in the four major paediatric HIV clinics of Abidjan, Côte d’Ivoire. All HIV-infected females aged 11–16 years were approached to participate in the study. A questionnaire assessing sexual behaviours and genital hygiene practices was administered to participants completed with a systematic vaginal swab collection. HPV genotyping was performed using the Anyplex II HPV28 Detection (Seegene). A logistic regression analysis was performed to identify factors associated with the presence of HPV infection. HPV immunisation was proposed free of charge to all participants.ResultsA total of 250 participants were included, with a median age of 13 years (IQR 11–14). Among them, 237 (94.8%) were on antiretroviral treatment with a median CD4 count of 660 (IQR 439–914) cells/mm3. The overall prevalence of at least one HPV was 3.6% (95% CI 1.6 to 6.7) and the prevalence of at least one carcinogenic HPV was 2.8% (95% CI 0.7 to 4.8). Vaginal cleansing was reported by 75 (30%) of participants, with a median age at initiation of 12 years (IQR 10–13). Sexual activity was self-reported by 12 (4.8%) participants with a median age at sexual debut of 11 years (IQR 10–14). HPV infection was associated with vaginal cleansing (adjusted OR=7.0 (95% CI 1.4 to 31.6)).ConclusionThe reported low prevalence of carcinogenic HPV infections supports the appropriateness of HPV immunisation in this population. The reported association between cleansing practices and HPV infection deserves further prospective longitudinal studies.

A cross-sectional study of 358 HIV-1-infected children and adolescents living in Sub-Saharan Africa treated with tenofovir disoproxil fumarate-based regimens for a median of 1.5 interquartile range [0.6-3.1 years] showed a loss of glomerular filtration rate estimated to be 0.41 mL/min/1.73 m per month of treatment. In contrast, there was no decrease depending on the duration of the previous antiretroviral treatment.

Summary Background The proportion of children living with HIV and receiving antiretroviral therapy (ART) in sub-Saharan Africa has increased greatly since 2006, yet the changes in their demographic characteristics and treatment outcomes have not been well described. We examine the trends in characteristics and outcomes of children living with HIV who were younger than 5 years at ART initiation, and compare outcomes over time and across country income groups. Methods We conducted a retrospective cohort analysis of data from children living with HIV who were younger than 5 years at ART initiation from 45 paediatric sites in 16 low-income, lower-middle-income, and upper-middle-income countries in sub-Saharan Africa (Benin, Burundi, Cote d'Ivoire, Democratic Republic of the Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia, and Zimbabwe). Outcomes were trends in patient characteristics at ART initiation (age, weight, height, and CD4%), and comparisons of mortality and loss to follow-up during ART over time and in various economic settings. We identified risk factors for mortality using Cox proportional hazards models. Each participating region had relevant institutional ethics review board approvals to contribute data to the analysis. Findings We included 32 221 children living with HIV and initiating ART younger than 5 years between Jan 1, 2006, and Dec 31, 2017. Median age at ART initiation was 20·4 months (IQR 9·4–36·0) in 2006–10, 19·2 months (8·3–33·6) in 2011–13, and 19·2 months (8·8–33·7) in 2014–17. Median age at ART initiation was 13·2 months (IQR 4·7–26·8) in upper-middle-income countries, 22·6 months (13·2–37·5) in lower-middle-income countries and 24·2 months (13·5–39·1) in low-income countries. The proportion of children initiating ART younger than 3 months increased from 770 (5·1%) of 14 943 children in 2006–10 to 728 (10·0%) of 7290 children in 2014–17. The proportion of children initiating ART with severe immunosuppression decreased from 5469 (74·7%) of 7314 children for whom CD4% data were available in 2006–10 to 2353 (55·2%) of 4269 children in 2014–17. Mortality at 24 months on ART decreased from 970 (6·5%) of 14 943 children in 2006–10 to 214 (2·9%) of 7290 children in 2014–17. Loss to follow-up was 20·5% (95% CI 20·1–21·0) overall, and was similar across time periods. In multivariable analysis, lower mortality was observed for more recent ART initiation cohorts (adjusted hazard ratio 0·70, 95% CI 0·63–0·79 for 2011–13; 0·53, 0·45–0·72 for 2014–17 vs 2006–10) and for those residing in an upper-middle-income country (0·42, 0·35–0·49 vs low-income countries). Interpretation Mortality declined significantly after universal ART recommendations for children younger than 2 years in 2010 and children younger than 5 years in 2013. However, substantial variations persisted across country income groups, and one in five children continue to be lost to follow-up. Targeted interventions are required to improve outcomes of children living with HIV, especially in the poorest countries. Funding National Institute of Allergy and Infectious Disease.

Aims A clinical study was conduct in HIV-infected children to evaluate the prophylactic doses of cotrimoxazole [sulfamethoxazole (SMX) and trimethoprim (TMP)] advised by the WHO. Methods Children received lopinavir-based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/40 mg of TMP once daily). A nonlinear mixed effects modelling approach was used to analyse plasma concentrations. Factors that could impact the pharmacokinetic profile were investigated. The model was subsequently used to simulate individual exposure and evaluate different administration schemes. Results The cohort comprised 136 children [average age: 1.9 years (range: [0.7–4]), average weight: 9.5 kg (range: [6–16.3])]. A dose per kg was justified by the significant influence of implementing an allometrically scaled body size covariate on SMX and TMP pharmacokinetics. SMX and TPM clearance were estimated at 0.49 l h−1/9.5 kg and 3.06 l h−1/9.5 kg, respectively. The simulated exposures obtained after administration of oral dosing recommended by the WHO for children from 10 to 15 kg were significantly lower than in adults for SMX and TMP. This could induce a reduction of effectiveness of cotrimoxazole. Simulations show that regimens of 30 mg kg−1 of SMX and 6 mg kg−1 of TMP in the 5–10 kg group and 25 mg kg−1 of SMX and 5 mg kg−1 of TMP in the 10–15 kg group are more suitable doses. Conclusions In this context of high prevalence of opportunistic infections, a lower exposure to cotrimoxazole in children than adults was noted. To achieve comparable exposure to adults, a dosing scheme per kg was proposed.

Background The NEVEREST-3 (South Africa) and MONOD-ANRS-12206 (Côte d’Ivoire, Burkina Faso) randomized trials found that switching to efavirenz (EFV) in human immunodeficiency virus–infected children >3 years old who were virologically suppressed by ritonavir-boosted lopinavir (LPV/r) was noninferior to continuing o LPV/r. We evaluated the cost-effectiveness of this strategy using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model. Methods We examined 3 strategies in South African children aged ≥3 years who were virologically suppressed by LPV/r: (1) continued LPV/r, even in case of virologic failure, without second-line regimens; continued on LPV/r with second-line option after observed virologic failure; and preemptive switch to EFV-based antiretroviral therapy (ART), with return to LPV/r after observed virologic failure. We derived data on 24-week suppression (, Using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model to project clinical outcomes, costs, and cost-effectiveness, we show that preemptively switching to efavirenz in virologically suppressed children >3 years old receiving ritonavir-boosted lopinavir (LPV/r) is cost saving compared with continued LPV/r.

There is limited information about malnutrition, growth evolution and metabolic changes among children initiated early on lopinavir-based antiretroviral therapy (ART) in Africa.HIV-1-infected children, age2 years were initiated on ART, as part of the MONOD ANRS 12206 project, conducted in Burkina Faso and Côte d'Ivoire. Weight-for-age, height-for-age and weight-for-height Z scores defined malnutrition [Z score less than -2 standard deviations (SDs)] using World Health Organization growth references. Biologic data were collected every 6 months. Factors associated with baseline malnutrition were evaluated using multivariate logistic regression, and with growth evolution in the first 24 months on ART using linear mixed models.Between 2011 and 2013, 161 children were enrolled: 64% were from Abidjan, 54% were girls. At ART initiation, median age was 13.7 months (interquartile range 7.7; 18.4), 52% were underweight (weight-for-age), 52% were stunted (height-for-age) and 36% were wasted (weight-for-height). Overall, baseline malnutrition was more likely for children living in Burkina Faso, with low birth weight, never breastfed and older age (12-24 months). Growth improved on ART, mainly within the first 6 months for weight, and was greater for the most severely malnourished children at baseline, but 8%-32% remained malnourished after 24 months. Over the 24-month period of ART, there was a significant increase of hypercholesterolemia and decrease of anemia and hypoalbuminemia.Prevalence of malnutrition was high before ART initiation. Even though growth improved on ART, some children remained malnourished even after 2 years of ART, highlighting the need for more active nutritional support.

The MONOD ANRS 12206 trial was designated to assess simplification of a successful lopinavir (LPV)-based antiretroviral treatment in HIV-infected children younger than 3 years of age using efavirenz (EFV; 25 mg/kg of body weight/day) to preserve the class of protease inhibitors for children in that age group. In this substudy, EFV concentrations were measured to check the consistency of an EFV dose of 25 mg/kg and to compare it with the 2016 FDA recommended dose. Fifty-two children underwent blood sampling for pharmacokinetic study at 6 months and 12 months after switching to EFV. We applied a Bayesian approach to derive EFV pharmacokinetic parameters using the nonlinear mixed-effect modeling (NONMEM) program. The proportion of midinterval concentrations 12 h after drug intake (C12 h) corresponding to the EFV therapeutic pharmacokinetic thresholds (1 to 4 mg/liter) was assessed according to different dose regimens (25 mg/kg in the MONOD study versus the 2016 FDA recommended dose). With both the 25 mg/kg/day dose and the 2016 FDA recommended EFV dose, simulations showed that the majority ofC12 hvalues were within the therapeutic range (62.6% versus 62.8%). However, there were more children underexposed with the 2016 FDA recommended dose (11.6% versus 1.2%). Conversely, there were more concentrations above the threshold of toxicity with the 25 mg/kg dose (36.2% versus 25.6%), withC12 hvalues of up to 15 mg/liter. Only 1 of 52 children was switched back to LPV because of persistent sleeping disorders, but hisC12 hvalue was within therapeutic ranges. A high EFV dose of 25 mg/kg per day in children under 3 years old achieved satisfactory therapeutic effective levels. However, the 2016 FDA recommended EFV dose appeared to provide more acceptable safe therapeutic profiles. (This study has been registered at ClinicalTrials.gov under identifier NCT01127204.)

Background: The 2016 World Health Organization guidelines recommend all children, 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and heightfor- age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and - 0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.

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]

BACKGROUND: We describe severe morbidity and health care resource utilization (HCRU) among HIV-infected children on antiretroviral therapy (ART) in Abidjan Cote dIvoire. METHODS: All HIV-infected children enrolled in an HIV-care program (2004-2009) were eligible for ART initiation until database closeout death ART interruption or loss to follow-up. We calculated incidence rates (IRs) of density per 100 child-years (CYs) for severe morbidity HCRU (outpatient care and inpatient care) and associated factors using frailty models with a Weibull distribution. RESULTS: Of 332 children with a median age of 5.7 years and median follow-up of 2.5 years 65.4% were severely immunodeficient by World Health Organization (WHO) criteria and all received cotrimoxazole prophylaxis. We recorded 464 clinical events in 228 children; the overall IR was 57.6/100 CYs [95% confidence interval (CI): 52.1 to 62.5]. Severe morbidity was more frequent in children on protease inhibitor (PI)-based ART compared to those on other regimens [adjusted hazards ratio (aHR): 1.83; 95% CI: 1.35 to 2.47] and to those moderately/severely immunodeficient compared to those not (aHR: 1.57; 95% CI: 1.13 to 2.18 and aHR: 2.53; 95% CI: 1.81 to 3.55 respectively). Of the 464 events 371 (80%) led to outpatient care (IR: 45.6/100 CYs) and 164 (35%) to inpatient care (IR: 20.2/100 CYs). In adjusted analyses outpatient care was significantly less frequent in children older than 10 years compared with children younger than 2 years (aHR: 0.49; 95% CI: 0.31 to 0.78) and in those living furthest from clinics compared with those living closest (aHR: 0.65; 95% CI: 0.47 to 0.90). Both inpatient and outpatient HCRU were negatively associated with cotrimoxazole prophylaxis. CONCLUSIONS: Despite ART HIV-infected children still require substantial utilization of health care services.

OBJECTIVES:To access the costs of care for Ivoirian children before and after initiating LPV/r-based antiretroviral therapy (ART) before the age of two. METHODS:We assessed the direct costs of care for all HIV-infected children over the first 12 months on LPV/r-based ART initiated

BACKGROUND There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modeling analysis in children ages 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-naive children of ages 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 5,826 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

Introduction: The 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. Methods: All 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. Results: Among 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. Conclusions: Fear 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. Copyright: - 2016 Dahourou DL et al;., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Clinical pharmacy activities in a pediatric inpatient department help to improve the management of patients clinically and economically. Objective: To assess the relevance of pharmaceutical interventions (PIs) in a pediatric inpatient department in Abidjan (Cote d'Ivoire). Materials and Methods: We carried out a cross-sectional, descriptive study from February to September 2014. The information collected was classified according to the classification of drug-related problems (DRPs) and PIs of the French Society of Clinical Pharmacy. The score assigned to each PI varied from PI 0 (without direct clinical impact) to PI 3 (vital clinical impact) as the importance of the potential clinical impact of the DRP was correlated to the severity of clinical consequences avoided by the PI. The relevance of PIs was assessed by their rate of acceptance by physicians and by the analysis of their clinical impact. Results: A total of 116 PIs were performed with 31% performed during medical rounds, 68.1% during patients' records analysis, and 0.1% on patient's admission. The main DRPs were related to noncompliance with recommendations (24.1%), overdose (21.1%), and underdosing (13.8%). The most important PIs were dose adjustment (31.8%), accuracy of drugs administration modalities (29.3%), and proposals of therapeutic choice (27.6%). The acceptance rate of PIs was highly significant (94.8%). The majority of PIs (67.3%) was assessed as having a significant clinical impact (PI 1 ) and 16.4% of PIs as very significant clinical impact (PI 2 ). A single PI (0.9%) was found with vital clinical impact. Conclusion: PIs performed were relevant and contributed to the therapeutic optimization and the prevention of iatrogenic events in pediatric inpatients.

SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons.OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries.DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs.RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages.CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

Background Nutritional care is not optimally integrated into pediatric HIV care in sub-Saharan Africa. We assessed the 6-month effect of a nutritional support provided to children living with HIV, followed in a multicentric cohort in West Africa. Methods In 2014-2016, a nutritional intervention was carried out for children living with HIV, aged under 10 years, receiving antiretroviral therapy (ART) or not, in five HIV pediatric cohorts, in Benin, Togo and Côte d’Ivoire. Weight deficiency was assessed using two definitions: wasting (Weight for Height Z-score [WHZ] for children Results Overall, 326 children were included, 48% were girls. At baseline, 66% were aged 5-10 years, 91% were on ART, and 17% were severely immunodeficient (CD4 p=0.907), nor by intervention groups (p-value=0.767). Conclusions This intervention had a limited effect on nutritional recovery and dietary diversity improvement. Questions remain on determining appropriate nutritional products, in terms of adherence, proper use for families and adequate energy needs coverage for children living with HIV. Trial registration PACTR202001816232398, June 01, 2020, retrospectively registered.