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Introduction: The large number of deaths among children with HIV is driven by poor antiretroviral treatment (ART) coverage among this cohort. The aim of the study was to assess the availability and stock-outs of paediatric and adult ART formulations in Kenya and Uganda across various regions and types of health facilities. Methods: A survey on availability and stock-outs of paediatric ART at health facilities was adapted from the standardized Health Action International–WHO Medicine Availability Monitoring Tool. All preferred and limited-use formulations, and three phased-out formulations according to the 2021 WHO optimal formulary list were included in the survey, as well as a selection of adult ART formulations suitable for older children, adolescents, and adults. Availability data were collected in June–July 2022 and stock-out data were obtained over the previous year from randomly selected public and private-not-for-profit (PNFP) facilities registered to dispense paediatric ART across six districts per country. All data were analysed descriptively. Results: In total, 144 health facilities were included (72 per country); 110 were public and 34 PNFP facilities. Overall availabilities of preferred paediatric ART formulations were 52.2% and 63.5% in Kenya and Uganda, respectively, with dolutegravir (DTG) 10 mg dispersible tablets being available in 70.2% and 77.4% of facilities, respectively, and abacavir/lamivudine dispersible tablets in 89.8% and 98.2% of facilities. Of note, availability of both formulations was low (37.5% and 62.5%, respectively) in Kenyan PNFP facilities. Overall availabilities of paediatric limited-use products were 1.1% in Kenya and 1.9% in Uganda. At least one stock-out of a preferred paediatric ART formulation was reported in 40.0% of Kenyan and 74.7% of Ugandan facilities. Nevirapine solution stock-outs were reported in 43.1% of Ugandan facilities, while alternative formulations for postnatal HIV prophylaxis were not available. Conclusi

Dose recommendations for lamivudine or emtricitabine in children with HIV and chronic kidney disease (CKD) are absent or not supported by clinical data. Physiologically based pharmacokinetic (PBPK) models have the potential to facilitate dose selection for these drugs in this population. Existing lamivudine and emtricitabine compound models in Simcyp® (v21) were verified in adult populations with and without CKD and in non-CKD paediatric populations. We developed paediatric CKD population models reflecting subjects with a reduced glomerular filtration and tubular secretion, based on extrapolation from adult CKD population models. These models were verified using ganciclovir as a surrogate compound. Then, lamivudine and emtricitabine dosing strategies were simulated in virtual paediatric CKD populations. The compound and paediatric CKD population models were verified successfully (prediction error within 0.5- to 2-fold). The mean AUC ratios in children (GFR-adjusted dose in CKD population/standard dose in population with normal kidney function) were 1.15 and 1.23 for lamivudine, and 1.20 and 1.30 for emtricitabine, with grade-3- and -4-stage CKD, respectively. With the developed paediatric CKD population PBPK models, GFR-adjusted lamivudine and emtricitabine dosages in children with CKD resulted in adequate drug exposure, supporting paediatric GFR-adjusted dosing. Clinical studies are needed to confirm these findings.

Introduction: Management of concomitant use of ART and TB drugs is difficult because of the many drug-drug interactions (DDIs) between the medications. This systematic review provides an overview of the current state of knowledge about the pharmacokinetics (PK) of ART and TB treatment in children with HIV/TB co-infection, and identifies knowledge gaps. Methods: We searched Embase and PubMed, and systematically searched abstract books of relevant conferences, following PRISMA guidelines. Studies not reporting PK parameters, investigating medicines that are not available any Longer or not including children with HIV/TB co-infection were excluded. ALL studies were assessed for quality. Results: In total, 47 studies met the inclusion criteria. No dose adjustments are necessary for efavirenz during concomitant first-Line TB treatment use, but intersubject PK variability was high, especially in children <3 years of age. Super-boosted Lopinavir/ritonavir (ratio 1:1) resulted in adequate Lopinavir trough concentrations during rifampicin co-administration. Double-dosed raltegravir can be given with rifampicin in children >4 weeks old as well as twice-daily dolutegravir (instead of once daily) in children older than 6 years. Exposure to some TB drugs (ethambutol and rifampicin) was reduced in the setting of HIV infection, regardless of ART use. Only Limited PK data of second-Line TB drugs with ART in children who are HIV infected have been published. Conclusions: Whereas integrase inhibitors seem favourable in older children, there are Limited options for ART in young children (<3 years) receiving rifampicin-based TB therapy. The PK of TB drugs in HIV-infected children warrants further research.

BACKGROUND: Many low- and middle-income countries (LMIC) are moving towards enforcing prescription-only access to antibiotics. This systematic literature review aims to assess the interventions used to enforce existing legislation prohibiting over-the-counter (OTC) sales of antibiotics in LMICs, their impact and examine the methods chosen for impact measurement including their strengths and weaknesses.METHODS: Both PubMed and Embase were systematically searched for studies reporting on impact measurement in moving towards prescription only access to antibiotics in LMICs. The PRISMA methodological review framework was used to ensure systematic data collection and analysis of literature. Narrative data synthesis was used due to heterogeneity of study designs.RESULTS: In total, 15 studies were included that assessed policy impact in 10 different countries. Strategies employed to enforce regulations prohibiting OTC sales of systemic antibiotics included retention of prescriptions for antibiotics by pharmacies, government inspections, engaging pharmacists in the design of interventions, media campaigns for the general public and educational activities for health care workers. A variety of outcomes was used to assess the policy impact; changes in antimicrobial resistance rates, changes in levels of antibiotic use, changes in trends of antibiotic use, changes in OTC supply of antibiotics, and changes in reported practices and knowledge of pharmacists, medicine sellers and the general public. Differences in methodological approaches and outcome assessment made it difficult to compare the effectiveness of law enforcement activities. Most effective appeared to be multifaceted approaches that involved all stakeholders. Monitoring of the impact on total sales of antibiotics by means of an interrupted time series (ITS) analysis and analysis of pharmacies selling antibiotics OTC using mystery clients were the methodologically strongest designs used.CONCLUS

BACKGROUND: Under-reporting of adverse drug reactions (ADRs) is a major challenge for pharmacovigilance in Africa. This study sets out to assess the level of awareness of Ghanaian patients about ADRs and ADR-reporting and explores how different patients in Ghana recognize an ADR and the steps they take when they experience an ADR.METHODS: This was a two-part study consisting of a survey to quantify the awareness of Ghanaian patients on ADRs and ADR-reporting, and in-depth interviews to explore how patients recognize an ADR and the steps they take thereafter. Participants were selected from 28 health care facilities (HCF) in rural and urban areas in 4 out of the 10 administrative regions of Ghana. Chi-square tests were used to examine associations between demographic variables and i) awareness of ADRs and ADR-reporting, ii) ADR experience and iii) awareness of the Ghana Food and Drug Authority (Ghana-FDA) and its patient reporting system (PRS). Only participants that indicated they experienced an ADR were included for the in-depth interviews. Data was investigated for participants' awareness of ADRs, ADR reporting and steps taken when they experience ADRs.RESULTS: Of the total 572 participants enrolled in the study, 14% indicated they were unaware of ADRs and were excluded. Of the remaining 491 participants, 38% had experienced an ADR, of which 67% reported the ADR, 68% of them reported it to a doctor. Only 3% of the 491 participants were aware of the Ghana-FDA's PRS. The interview phase consisted of 33 patients who had experienced an ADR. Three key findings from the interview phase were; most participants recognized an ADR themselves, the symptoms of the ADR were the most mentioned reason for reporting and participants experienced a wide variety of obstacles in ADR-reporting.CONCLUSIONS: Most Ghanaian patients appear unaware of or unable/unwilling to use formal national channels for ADR reporting like the Ghana-FDA PRS. Motivation for ADR rep