A5059971268- Tuberculosis Research and Epidemiology
- Antibiotics Pharmacokinetics and Efficacy
- Pharmaceutical studies and practices
- HIV/AIDS drug development and treatment
- Drug Transport and Resistance Mechanisms
- Cervical Cancer and HPV Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Hepatitis B Virus Studies
- Pharmacogenetics and Drug Metabolism
- Pneumonia and Respiratory Infections
- Genital Health and Disease
- Pharmacological Effects and Toxicity Studies
- Antimicrobial Resistance in Staphylococcus
- Cancer therapeutics and mechanisms
- Ocular Diseases and Behçet’s Syndrome
- Herpesvirus Infections and Treatments
- Infectious Diseases and Tuberculosis
- Reproductive tract infections research
- Pharmacological Effects of Natural Compounds
- Adolescent Sexual and Reproductive Health
- Cerebral Venous Sinus Thrombosis
- Respiratory and Cough-Related Research
Desmond Tutu HIV Foundation
2016-2025
Stellenbosch University
2014-2025
University of Cape Town
2021-2024
Tygerberg Hospital
2014-2017
Brooklyn Chest Hospital
2016
Abstract Background Paediatric pharmacokinetic and safety data for clofazimine are limited. We described the pharmacokinetics of in South African children treated multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB). Methods Children <18 years being routinely MDR/RR-TB were eligible study participation. Soft gel capsules (Novartis Pharma AG) administered using WHO-recommended weight-based dosing. Sparse semi-intensive sampling was completed at baseline, Week 2 16. Clofazimine...
Rifampicin doses of 40 mg/kg in adults are safe and well tolerated, may shorten anti-TB treatment improve outcomes, but have not been evaluated children.To characterize the pharmacokinetics safety high rifampicin children with drug-susceptible TB.The Opti-Rif trial enrolled dosing cohorts 20 aged 0-12 years, incremental dose escalation each subsequent cohort, until achievement target exposures or concerns. Cohort 1 opened a 15 for 14 days, single higher (35 mg/kg) on day 15. Pharmacokinetic...
Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment prevention, but the existing pharmacokinetic data in have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient meta-analysis available studies determine optimal dosing children.
Moxifloxacin is a priority drug for treating rifampicin-resistant tuberculosis (RR-TB). We assessed the pharmacokinetics of child-friendly, dispersible 100 mg tablet moxifloxacin formulation (dispersed in water) compared to standard 400 non-dispersible (crushed and suspended children evaluated current dosing recommendations. The CATALYST trial investigated with RR-TB. Children were enrolled South Africa, India Philippines. Intensive pharmacokinetic sampling was undertaken while taking...
This study sought to assess the feasibility of conducting a phase III HIV prevention trial using multivalent human papillomavirus (HPV) vaccine (Gardasil; Merck, Whitehouse Station, NJ).A total 479 sexually active women aged 16-24 years in Western Cape, South Africa, were enrolled Efficacy HPV Vaccine Reduce Infection (EVRI) Trial. Of these, 402 negative, nonpregnant, and randomized 1:1 receive Gardasil or saline placebo vaccine. doses administered at enrollment, month 2, 6, participants...
Objective To estimate the prevalence and describe patterns of concurrent human papillomavirus (HPV) STIs associated factors among HIV-negative young Western Cape, South African women participating in Efficacy HPV Vaccine to Reduce HIV Infection (EVRI) trial. Methods aged 16–24 years old were enrolled EVRI trial ( NCT01489527 ) randomised receive licensed four-valent vaccine or placebo. At study entry, participants clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2),...
In 2010, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using current dispersible fixed-dose combination (FDC) tablet rifampicin/isoniazid/pyrazinamide; 75/50/150 mg, and suggest a new FDC with weight bands.Children drug-susceptible tuberculosis in Malawi South Africa underwent pharmacokinetic sampling while receiving...
Moxifloxacin is a recommended drug for rifampin-resistant tuberculosis (RR-TB) treatment, but there limited pediatric pharmacokinetic and safety data, especially in young children. We characterize moxifloxacin population pharmacokinetics QT interval prolongation evaluate optimal dosing children with RR-TB.Pharmacokinetic data were pooled from 2 observational studies South African RR-TB routinely treated oral once daily. The Fridericia-corrected (QTcF)-interval characterized NONMEM....
Fluoroquinolones are a key component of multidrug-resistant tuberculosis treatment. We describe the first reported case probable levofloxacin-associated intracranial hypertension in 6-year-old girl with pulmonary tuberculosis. The highlights potential risk secondary patients who require prolonged fluoroquinolone therapy and need for ophthalmologic screening children suggestive signs symptoms.
Lopinavir-ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs children high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir-ritonavir. We describe pharmacokinetics drug-drug lopinavir-ritonavir drugs routinely used for A combined population pharmacokinetic model was developed jointly lopinavir ritonavir 32 (16...
Levofloxacin is used for treatment and prevention of rifampicin-resistant (RR)-TB in children. Recent data showed higher exposures with 100 mg dispersible compared non-dispersible tablet formulations potentially important dosing implications We aimed to verify better characterize this finding.We conducted a crossover pharmacokinetic trial children aged ≤5 years receiving levofloxacin RR-TB preventive therapy. Pharmacokinetic sampling was done after 15-20 mg/kg doses crushed 250 formulations....
HPV antibodies are a marker of past exposure to the virus. Our objective was assess serostatus pre- and post-vaccination among HIV-negative women.Women aged 16-24 years old were randomized in placebo controlled trial utilizing 4-valent (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received 4vHPV or following three dose schedule. Sera collected at Day 1 Month 7 for assessment 6, 11, 16, 18 neutralizing antibody levels using multiplex competitive Luminex immunoassay...
BACKGROUND: High-dose isoniazid (INH H ) (15–20 mg/kg/day) could be administered to overcome low-level INH resistance, but pharmacokinetic data are sparse. METHODS: This observational study included South African children (<15 years) receiving as preventive therapy, or treatment for multidrug-resistant TB (MDR-TB) exposure disease. Pharmacokinetic sampling was performed after an dose of 20 mg/kg. Non-compartmental analysis and multivariable regression models were used evaluate...
There are no pharmacokinetic data in children on terizidone, a pro-drug of cycloserine and World Health Organization (WHO)-recommended group B drug for rifampicin-resistant tuberculosis (RR-TB) treatment. We collected <15 years routinely receiving 15-20 mg/kg daily terizidone RR-TB developed population model assuming 2-to-1 molecular ratio between cycloserine. included 107 with median (interquartile range) age weight 3.33 (1.55, 5.07) 13.0 (10.1, 17.0) kg, respectively. The pharmacokinetics...
Given the high prevalence of multidrug-resistant (MDR)-TB in HIV burden settings, it is important to identify potential drug-drug interactions between MDR-TB treatment and widely used nucleoside reverse transcriptase inhibitors (NRTIs) HIV-positive children. Population pharmacokinetic models were developed for lamivudine (n = 54) abacavir 50) 54 children established on NRTIs; 27 with (combinations high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, fluoroquinolones,...
Abstract Background Linezolid, an important component of rifampicin- and multidrug-resistant tuberculosis (RR/MDR-TB) treatment, is associated with treatment-limiting toxicities, including anemia. Patient-level linezolid pharmacokinetic risk factors for anemia have not been well described in children treated RR/MDR-TB. Methods We evaluated the pharmacokinetics longitudinal hemoglobin data to validate existing population model. assessed impact developing a prospectively enrolled cohort...
The complexity of the currently registered dosing schedules for bedaquiline and delamanid is a barrier to uptake in drug‐resistant tuberculosis treatment across all ages. A simpler once‐daily schedule critical ensure patient‐friendly regimens with good adherence. We assessed expected drug exposures proposed doses adults compared novel model‐informed strategies children current World Health Organization (WHO) recommended dosing. reference individual virtual pediatric population were generated...
Treatment options for children with Rifampicin-resistant tuberculosis (RR-TB) remain limited, and para-aminosalicylic acid (PAS) is still a relevant component of treatment regimens. Prevention resistance to companion drugs by PAS dose related, at higher concentrations, may exhibit significant bactericidal activity in addition its bacteriostatic properties. The optimal dosing uncertain, specifically delayed-release granule preparations, which are the most used. A population pharmacokinetic...