Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
- Conditions
- Acquired Immunodeficiency SyndromeTuberculosis
- Registration Number
- NCT02348177
- Lead Sponsor
- Drugs for Neglected Diseases
- Brief Summary
The purpose of this study is to determine the lopinavir levels in blood of HIV and TB infected children (3-15kg) when given lopinavir/ritonavir in a 1:1 ratio with rifampicin containing TB regimen and its safety.
- Detailed Description
This is a multicentre, open label, non-randomized, prospective, noninferiority study to compare the pharmacokinetics of lopinavir administered with superboosting (LPV/r 1:1) and concurrent RIF treatment or with standard boosting (LPV/r 4:1) without concurrent RIF treatment, and to assess the safety, tolerance, and virological effect of superboosting in HIV-TB co-infected infants and children weighing \>3 kg and ≤15 kg.
LPV/r will be administered as the liquid 80/20 mg/mL formulation (4:1 standard boosting ratio). During anti-TB treatment, additional RTV liquid formulation will be provided to deliver a 1:1 superboosting ratio of LPV to RTV. Actual doses for antiretrovirals and anti-TB drugs will be based on the South African (SA) weight band dosing recommendations and provided as per the site standard of care.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 96
- Documentation of a confirmed diagnosis of HIV-1 infection following SA clinical guidelines
- Weight >3kg ≤15 kg at enrolment
- > 42 weeks gestational age
- On LPV/r-based therapy or about to start a LPV/r-based antiretroviral combination therapy with 2 NRTIs [ABC+3TC or AZT+3TC or d4T+3TC]
- Clinical diagnosis of TB requiring RIF-based therapy
- Parent or legal guardian able and willing to provide written informed consent and able to attend study visits.
- For neonates, less than 42 weeks gestation and 14 days old
- Concomitant/chronic treatment with potent enzyme-inducing/inhibiting drugs other than those in the study treatments . See Appendix E (minor inducers/inhibitors and drugs used as part of management of the condition are allowed eg. Steroids)
- Anticipation at the start that anti-TB treatment duration will be longer than 9 months
- Any other condition/finding that, in the investigator's opinion, would compromise the child's participation in this study eg. alanine transferase (ALT) more than 10 times upper limit of normal (ULN), or chronic renal, hepatic or gastrointestinal disease such as malabsorption.
- Children with known malignancies and contraindications to taking LPV/r
- Treatment with experimental drugs for any indication within 30 days prior to study entry; participation in another study may be approved by the study team.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Modelled C0/morning trough Predose Proportions of children treated with modelled lopinavir morning C0/morning trough \<1mg/L at each of the intensive PK evaluations.
- Secondary Outcome Measures
Name Time Method ALT baseline, PK1, PK2, PK3 Safety and tolerability of superboosting focusing on liver functions through clinical and biochemical monitoring.
C0/morning trough Predose Proportions of children with observed lopinavir morning trough, C0/morning trough \<1mg/L at each of the intensive PK evaluations
ECG baseline, 2 weeks after LPV/r 1:1, PK1 Potential superboosting cardiac effect monitored by electrocardiogram at the beginning of anti-TB and HIV concomitant therapy
Trial Locations
- Locations (5)
Enhancing Care Foundation; Wendworth Hospital
🇿🇦Durban, South Africa
Perinatal HIV Research Unit
🇿🇦Johannesburg, South Africa
Empilweni Services and Research Unit
🇿🇦Johannesburg, South Africa
Shandukani Research WRHI
🇿🇦Johannesburg, South Africa
The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch
🇿🇦Cape Town, Western Cape, South Africa