First-Line Antituberculosis Drug Concentrations in Infants With HIV and a History of Recent Admission With Severe Pneumonia.

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.

Evaluating the Effectiveness of Interactive Virtual Patients for Medical Education in Zambia: Randomized Controlled Trial.

BACKGROUND: Zambia is facing a severe shortage of health care workers, particularly in rural areas. Innovative educational programs and infrastructure have been established to bridge this gap; however, they encounter substantial challenges because of constraints in physical and human resources. In response to these shortcomings, strategies such as web-based and blended learning approaches have been implemented, using virtual patients (VPs) as a means to promote interactive learning at the Levy Mwanawasa Medical University (LMMU) in Zambia. OBJECTIVE: This study aimed to evaluate the students' knowledge acquisition and acceptance of 2 VP medical topics as a learning tool on a Zambian higher education e-learning platform. METHODS: Using a mixed methods design, we assessed knowledge acquisition using pre- and posttests. In a randomized controlled trial setting, students were assigned (1:1) to 2 medical topics (topic 1: appendicitis and topic 2: severe acute malnutrition) and then to 4 different learning tools within their respective exposure groups: VPs, textbook content, preselected e-learning materials, and self-guided internet materials. Acceptance was evaluated using a 15-item questionnaire with a 5-point Likert scale. RESULTS: A total of 63 third- and fourth-year Bachelor of Science clinical science students participated in the study. In the severe acute malnutrition-focused group, participants demonstrated a significant increase in knowledge within the textbook group (P=.01) and the VP group (P=.01). No substantial knowledge gain was observed in the e-learning group or the self-guided internet group. For the appendicitis-focused group, no statistically significant difference in knowledge acquisition was detected among the 4 intervention groups (P=.62). The acceptance of learning materials exhibited no substantial difference between the VP medical topics and other learning materials. CONCLUSIONS: In the context of LMMU, our study found that VPs were well accepted and noninferior to traditional teaching methods. VPs have the potential to serve as an engaging learning resource and can be integrated into blended learning approaches at LMMU. However, further research is required to investigate the long-term knowledge gain and the acceptance and effectiveness of VPs in medical education. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR202211594568574; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=20413.

Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change.

BACKGROUND: Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment. METHODS: This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r. RESULTS: In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough <1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin. CONCLUSION: Double-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir.