A5012522909- HIV/AIDS drug development and treatment
- HIV/AIDS Research and Interventions
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Tuberculosis Research and Epidemiology
- Pharmaceutical studies and practices
- HIV-related health complications and treatments
- Child Nutrition and Water Access
- Pharmacological Effects and Toxicity Studies
- Health Systems, Economic Evaluations, Quality of Life
- Pneumonia and Respiratory Infections
- Adolescent Sexual and Reproductive Health
- Global Maternal and Child Health
- Diagnosis and treatment of tuberculosis
- Drug Transport and Resistance Mechanisms
- Ethics in Clinical Research
- Hemoglobinopathies and Related Disorders
- Neonatal and Maternal Infections
- Pharmacogenetics and Drug Metabolism
- Statistical Methods in Clinical Trials
- Infant Development and Preterm Care
- Global Health and Epidemiology
- Cytomegalovirus and herpesvirus research
- Adolescent and Pediatric Healthcare
- Chronic Lymphocytic Leukemia Research
University Teaching Hospital
2012-2024
University of Zambia
2007-2024
University of Lusaka
2024
Two thirds of children with tuberculosis have nonsevere disease, which may be treatable a shorter regimen than the current 6-month regimen.We conducted an open-label, treatment-shortening, noninferiority trial involving nonsevere, symptomatic, presumably drug-susceptible, smear-negative in Uganda, Zambia, South Africa, and India. Children younger 16 years age were randomly assigned to 4 months (16 weeks) or 6 (24 standard first-line antituberculosis treatment pediatric fixed-dose...
Mortality of children with Severe Acute Malnutrition (SAM) in inpatient set-ups sub-Saharan Africa still remains unacceptably high. We investigated the prevalence and effect diarrhea HIV infection on treatment outcome complicated SAM receiving units. A cohort 430 aged 6-59 months old admitted to Zambia University Teaching Hospital's stabilization centre from August December 2009 were followed. Data nutritional status, socio-demographic factors, admission medical conditions collected up...
Introduction A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions sustain high levels adherence. Methodology/Principal Findings Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, medication event monitoring...
Background: There are few data on predictors of HIV progression in untreated children resource-limited settings. Methods: Children with Antibiotic Prophylaxis (CHAP) was a randomized trial comparing cotrimoxazole prophylaxis placebo HIV-infected Zambian children. The prognostic value baseline characteristics investigated using Cox models. Results: Five hundred fourteen aged 1 to 14 (median 5.5) years contributed 607 follow-up (maximum 2.6 years). Half were boys, and 67%, the mother primary...
Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear.CHAP was a randomized trial comparing cotrimoxazole with placebo HIV-infected children Zambia where background bacterial resistance to is high. We compared causes of hospital admissions, antibiotic use between groups.Of 534 (median age, 4.4 years; 32% 1-2 years), 186 died 166 had one or more admissions not ending death. associated lower mortality, both outside...
WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) Africa, where most live. We aimed to compare stavudine, zidovudine, or abacavir as dual triple fixed-dose-combination tablets with lamivudine and nevirapine efavirenz.In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled from one centre Zambia...
Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment largely extrapolated from adult studies. Trials adults with smear-negative suggest that can be effectively shortened 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced many countries, making the implementation World Health Organisation (WHO)-revised dosing recommendations feasible. The...
Background.Data on the population effectiveness of cotrimoxazole prophylaxis and antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–infected African children are few. Methods.A total 534 Zambian with HIV infection were randomized to receive daily or placebo Children Antibiotic Prophylaxis trial. Following trial closure, who received initiated prophylaxis, all observed a closed cohort. Mortality hospital admission rates compared, over calendar time, 9-month periods:...
Objective: Triomune Baby and Junior have been developed in response to the urgent need for appropriate paediatric fixed-dose combination antiretroviral tablets, with higher nevirapine stavudine lamivudine ratios than adult accordance recommendations. We determined whether this ratio results optimal exposure target population. Methods: Seventy-one Zambian children were treated or dosed according weight bands. After 4 weeks more, a 12-h pharmacokinetic curve was recorded. Antiretroviral plasma...
Abstract Background Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced 2015. We report the first pharmacokinetic data for these FDC Zambian and South African children treatment-shortening SHINE trial. Methods Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, 4 daily, respectively (rifampicin/isoniazid/pyrazinamide...
Abstract Background Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH children not living HIV treated for nonsevere TB the SHINE trial. Methods was a randomized trial that enrolled aged <16 years smear-negative, who were to receive 4 versus 6 months treatment followed 72 weeks. assessed relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse...
Objective: To assess the cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children Zambia, as implementation at local health centre level has yet to be undertaken many resource-limited countries despite recommendations recent updated World Health Organization (WHO) guidelines. Design: A probabilistic decision analytical model HIV/AIDS progression based on CD4 cell percentage (CD4%) was populated with data from placebo-controlled Children HIV Antibiotic Prophylaxis trial that...
Objective To investigate nevirapine concentrations in African HIV-infected children receiving divided Triomune tablets (stavudine+lamivudine+nevirapine). Design Cross-sectional study. Methods Steady-state plasma were determined Malawian and Zambian aged 8 months to 18 years routine outpatient settings. Predictors from height-for-age, body mass index (BMI)-for-age, age, sex, post-dose sampling time dose/m 2 /day investigated using centre-stratified regression with backwards elimination (...
The impact of cotrimoxazole (CTX) on growth and/or anemia was investigated in 541 human immunodeficiency virus-infected, antiretroviral therapy–naive Zambian children enrolled the Children with HIV Antibiotic Prophylaxis trial. Compared randomized to receive placebo, CTX had slower decreases weight-for-age (P = .04) and height-for-age .01), greater increase hemoglobin level .01). These findings argue for expanded early use.
Aims Using a model‐based approach, the efavirenz steady‐state pharmacokinetics in African children is characterized, quantifying demographic and genotypic effects on drug's disposition. Simulations are also conducted allowing prediction of optimized doses this population. Methods We modelled population Ugandan Zambian using nonlinear mixed‐effects modelling. Individual mid‐dose concentrations were derived simulations explored genotype‐based dose optimization strategies. Results A...
Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this is usually only considered cases of prolonged symptoms antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case and reduce mortality.We did a stepped-wedge cluster-randomised trial 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, Zambia) high incidence tuberculosis. Children younger than 5 years WHO-defined received...
Fixed-dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Triomune Baby Junior; Cipla Ltd) are simpler cheaper than liquid formulations have correct dose ratios for human immunodeficiency virus-infected children. However, they cannot be used escalation (DE) of nevirapine.Children were randomized to initiate antiretroviral therapy with full-dose (FD) or Junior in the morning evening) versus DE (half-dose 14 days [Triomune stavudine-lamivudine {Lamivir-S}...
Abstract Background We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving twice daily (BID) rifampicin-based tuberculosis (TB) treatment compared once (OD) without rifampicin. Methods Infants HIV aged 1–12 months, weighing ≥3 kg, and BID rifampicin or OD were eligible. Six blood samples taken over 12 24 hours (OD). Dolutegravir pharmacokinetic parameters, viral load (VL) data, adverse events (AEs) reported. Results Twenty-seven of 30 enrolled...
In children with severe acute malnutrition (SAM) tuberculosis is common, challenging to diagnose, and often fatal. We developed treatment decision algorithms (TDAs) for under the age of 5 years SAM.
There is an urgent need to optimize cotreatment for children with tuberculosis and HIV infection. We described nevirapine pharmacokinetics in Zambian aged less than 3 years, cotreated nevirapine, lamivudine stavudine fixed-dose combination (using WHO weight bands) rifampicin-based antituberculosis treatment.Twenty-two received antiretroviral therapy (ART) concurrently 4 weeks before pharmacokinetic sampling. Plasma concentrations were determined samples taken immediately before, 1, 2 6 h...
Abstract Background We evaluated the pharmacokinetics of tenofovir alafenamide fumarate (TAF) and in a subset African children enrolled CHAPAS-4 trial. Methods Children aged 3–15 years with human immunodeficiency virus infection failing first-line antiretroviral therapy were randomized to emtricitabine/TAF versus standard-of-care nucleoside reverse transcriptase inhibitor combination, plus dolutegravir, atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. Daily was dosed...