Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB

Drugs for Neglected Diseases

Status and phase

Completed

Phase 4

Conditions

Tuberculosis

Acquired Immunodeficiency Syndrome

Treatments

Drug: lopinavir with ritonavir in 1:1 ratio

Drug: Lopinavir/ritonavir 4:1

Study type

Interventional

Funder types

Other

Identifiers

NCT02348177

DNDiHIVPed001

Details and patient eligibility

About

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.

Full 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.

Enrollment

96 patients

Sex

All

Ages

2+ weeks old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

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.