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BACKGROUND: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. METHODS: Infants with HIV aged 1-12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. RESULTS: Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1-9.9), weight was 6.3 kg (5.6-7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)0-24h 0.91 (95% confidence interval, .59-1.42), Ctrough 0.95 (0.57-1.59), Cmax 0.87 (0.57-1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir Ctrough

Optimal antituberculosis therapy is essential for favorable clinical outcomes. Peak plasma concentrations of first-line antituberculosis drugs in infants with living HIV receiving WHO-recommended dosing were low compared with reference values for adults, supporting studies on increased doses of first-line TB drugs in infants.

References Antiretroviral therapy for HIV infection in adults and adolescents. Public Health Approach 2010 Revision. World Health Organization. Geneva, Switzerland; ISBN 978 92 4 159976 4. Integrated national guidelines on [...], Introduction: In 2011 Uganda recommended boosted atazanavir (ATV/r) as the preferred PI for second line due to once daily dosing, replacing aluvia (LPV/r) [1, 2]. The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was performed in a high?income setting, on patients with prior PI use and resistance testing [2, 3]. There are no RCTs or observational studies comparing use of ATV/r with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub?Saharan Africa [3, 4]. The Infectious Diseases Institute (IDI) has a large second line cohort (>1838). This aims to compare clinical, immunologic and virologic response of LPV/r versus ATV/r at IDI. Methods: Retrospective cohort analysis on routinely collected data of patients switched to second line with NRTI backbones TDF/3TC or FTC, AZT/3TC, ABC/3TC from January 2009 to December 2013. Students T?tests and Chi?square tests were used in this analysis. Results: A total of 1286 (73.5% female) patients were switched to LPV/r 991 (77%) and ATV/r 295 (23%) (p Conclusions: This is an observational study based on our experience at IDI. Like elsewhere in Africa, there is no routine viral load testing, making it difficult to get sensitive analysis of data on ART efficacy within routine clinical practice. Nevertheless, this observational study is reassuring in terms of efficacy of both ATV/r and LPV/r for patients failing first line therapy in our setting.

Figure 1: Maximum drug concentrations in comparision to reference ranges. [Figure omitted] References Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs. 2002;62: 2169?83. Chideya S, Winston CA, [...], Introduction: There is limited data available on exposure to anti?tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti?TB drugs in the HIV/TB co?infected population in Sub?Saharan Africa. Our objective is to describe the concentration of anti?TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB. Methods: This study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti?TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti?TB treatment using ultraviolet high?performance liquid chromatography (UV?HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies. Results: We started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m[sup.2] and a median CD4 cell count of 142 cells/?. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R. Levels of H were found to be below the reference ranges (3?6 ?/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8?24 ?/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2?D2.1 ?/mL and 4.0?D3.1 ?/mL for E and 41.6?D13.1 ?/mL and 42.6?D16.4 ?/mL for Z. Conclusion: We observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co?infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.

Background: Mortality among children under 5 years of age admitted to malnutrition units in sub-Saharan Africa remains high. The burden of HIV infection, a major risk factor for mortality among patients with severe acute malnutrition (SAM), has reduced due to concerted prevention and treatment strategies. None the less, anecdotal reports from the malnutrition unit at Uganda's National Referral Hospital (NRH) indicate that there is high mortality among patients with severe acute malnutrition (SAM) in routine care. Uganda has recently adopted the revised World Health Organization (WHO) treatment guidelines for SAM to improve outcomes. The mortality among children with SAM in routine care has not been recently elucidated. We report the magnitude and factors associated with mortality among children under 5 years of age admitted to the NRH for routine care of SAM.Methods: This was a cohort study of all severely malnourished children admitted to the NRH between June and October 2017. The primary outcome was two-week mortality. Mortality was calculated using simple proportions and Cox regression analysis was used to determine factors associated with time to mortality. Data was entered into Epidata and analysed using Stata v14.Results: Two-hundred-sixty (98.5%) children: 59.6% male; mean age 14.4 (SD 9.4) months, completed two weeks of follow-up. Of these, 25.2% (95% CI 19.9-30.4%) died. In-hospital mortality was 20.7% (95% CI15.9-25.6%). The prevalence of HIV infection was 12.2%. Factors associated with mortality included: positive HIV status (AHR 2.2, (95% CI; 1.2-4.2), p = 0.014), bacteraemia (AHR 9 (95% CI 3.4-23.0), p < 0.001, and low glomerular filtration rate (eGFR), AHR 3.2; (95% CI 1.7-6.3), p = 0.001).Conclusions: A 25% mortality among children with severe malnutrition remains unacceptably high despite significant reduction in HIV prevalence. Children with SAM who are HIV infected, have eGFR below 60 mL/min/1.73m2 or have bacteraemia, are more likely to die. Further studies to explore the relationship between eGFR and mortality among children with SAM are needed. Studies to establish efficacious antibiotics are urgently required to inform treatment guidelines for children with SAM. [ABSTRACT FROM AUTHOR]

Pneumonia remains an important cause of morbidity and mortality among children in low- and middle-income countries. Poor outcomes are associated with undernutrition. Nutritional supplementation may be beneficial. We examined the effect of supplementation with lipid-based ready-to-use therapeutic food (RUTF) on the body composition of children with severe pneumonia. Non-severely malnourished children (6-59 months) with severe pneumonia enrolled into the Children's Oxygen Administration Strategies and Nutrition trial in Uganda and Kenya, and randomized to receive a diet supplemented with RUTF (500 Kcal/day) for 56 days versus usual diet alone (control) were included. We assessed arm anthropometry and bioimpedance analysis at admission and days 28, 90, and 180 of follow-up. We used mixed effects linear regression to compare body composition between groups. We included 737 participants (369 in intervention; 368 in control group). The median age was 16 months (IQR; 9, 26), and 58.1% were male. Overall, baseline mean arm fat area (AFA), arm muscle area, and arm muscle circumference were 5.8 ± 1.8 cm2, 11.6 ± 2.3 cm2, and 12.3 ± 1.2 cm2, respectively. The mean fat mass and fat-free mass calculated in 116 participants were 5.5 ± 1.5 kg and 5.5 ± 1.5 kg, respectively. There were modest increases in most body composition parameters. RUTF significantly increased AFA at days 28 and 90 but not at day 180 (P-value = .03, .02, and .99, respectively). RUTF did not change other body composition parameters. Despite initial increases in AFA, RUTF did not change the body composition of children with severe pneumonia., (© The Author(s) [2025]. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Pneumonia remains the commonest cause of ill health and mortality among children worldwide. Severe undernutrition increases the mortality risk among children with pneumonia. While children with pneumonia are at increased risk of developing malnutrition, the impact of pneumonia on mortality and nutritional status of non-severely undernourished children is not well described. The impact of nutritional supplementation on mortality and nutritional status in this population is not well understood. This review will collate available evidence on the all-cause mortality and anthropometric indices outcomes following pneumonia, as well as the impact of nutritional supplementation on mortality and anthropometry among non-severely malnourished children with pneumonia., Methods: The review will be done using a priori criteria developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data will be obtained from data bases, grey literature, and bibliographies. An experienced librarian will conduct article search in PUBMED, MEDLINE, EMBASE, Web of Science, Google scholar, and Scopus. Retrieved articles will be entered in Endnote ver 9.0, duplicates removed, and transferred to Epi-reviewer for screening and data abstraction. Risk of bias in the included articles will be assessed using standard criteria. Heterogeneity will be assessed using I 2 -statistic and sub-group analysis will be done. Data will be analysed using both narrative and quantitative synthesis. Quantitative synthesis will be done using DeSimonian and Laird Random-effects model in STATA ver 15.0., Conclusions: The results will provide baseline information about the mortality and anthropometric outcomes of pneumonia among non-severely malnourished children as well as the potential effect of nutritional supplementation on these outcomes. This will provide a basis to explore the potential for nutritional supplementation improving clinical outcomes like mortality and occurrence of severe acute malnutrition among children with severe pneumonia worldwide., Registration: The review has been registered in PROSPERO (CRD42021257272; 15 July 2021)., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Nalwanga D et al.)

Background: Severe Pneumonia is still the leading cause of morbidity and mortality among children worldwide. Many children with severe pneumonia are reported to die in hospital as well as following discharge due to malnutrition. Severe pneumonia is a catabolic illness, which predisposes to severe malnutrition. WHO and United Nations Children's Fund (UNICEF), recommend 'continued' feeding but do not give any specific recommendations for nutritional support. This could influence health workers' and caregivers' attitudes, practices and understanding regarding the topic. This study aimed to explore the attitudes, practices and understanding of health workers regarding the relationship between severe pneumonia and malnutrition., Methods: We conducted an exploratory qualitative study among health workers and caregivers of children hospitalized with severe pneumonia at Mulago National Referral Hospital in Uganda. Data were collected using focus-groups involving caregivers and key informant interviews with health workers and analysed using the content-thematic analysis approach. Both manual coding and Atlas Ti software were used to support the analysis., Results: Some of the health workers and caregivers were aware of the relationship between severe pneumonia and malnutrition to various degrees, citing reduced appetite, difficulty in breathing and persistent vomiting as pathways to malnutrition in patients with severe pneumonia, which called for a balanced diet and more frequent breastfeeding. Suppressed immunity in malnourished children was mentioned as the pathway to severe pneumonia. Some caregivers confessed not knowing anything about the relationship between the two conditions., Conclusion: Attitudes, practices and understanding regarding the deadly relationship between severe pneumonia and malnutrition among care givers could further be improved by health education and mass sensitization. Clarifying practice guidelines could further enhance attitudes and practices of health workers to reduce preventable pneumonia deaths., Competing Interests: Competing interests The authors declare that they have no competing interests.