HIV/AIDS Tuberculosis
Conditions
Interventions
Superboosting LPV/r 1:1
Sponsors
Drugs for Neglected Diseases Initiative
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Documentation of a confirmed diagnosis of HIV-1 infection following SA clinical guidelines Weight >3kg and 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 rifampicin-based therapy Parent or legal guardian able and willing to provide written informed consent and able to attend study visits.
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate that the proportion of subjects achieving LPV C0/morning trough above 1mg/L during superboosting of LPV with RTV (in a 1:1 ratio) while on RIF-based anti-TB treatment, is not inferior the proportion of subjects achieving LPV C0/morning trough above 1 mg/L during ART with LPV/r (in a 4:1 ratio) in the absence of anti-TB treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of LPV/r liquid formulation in HIV-infected infants and children with RTV superboosting (1:1 ratio LPV/r) with concomitant RIF-based anti-TB treatment. ;Compare the model-based estimates of the LPV PK measures of exposure (C0/morning trough, C12/evening trough, Cmax, AUC) during anti-TB treatment and superboosting vs. during treatment with standard LPV/r doses 1 month after completing TB therapy.;To explore the effects of age, weight, sex, initial severity of tuberculosis and anthropometric measurements on LPV & RTV pharmacokinetics, i.e. exposure, C12/evening trough, Cmax and C0/morning trough concentrations with/without concomitant anti-TB treatment.;To determine the pharmacokinetics of anti-TB drugs concomitantly administered with superboosted PI.;To assess adherence to therapy ;To describe viral load evolution before, during and after superboosting and monitor resistance in children failing therapy;To compare abacavir (ABC) blood levels during and after co-treatment with rifampicin based anti-TB therapy;To determine the pharmacokinetics of anti-TB drugs concomitantly administered with superboosted PI. | — |
Countries
South Africa
Contacts
Public ContactMarc Lallemant
Head of Paediatric HIV Program
Outcome results
None listed