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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02348177
Recruitment Status : Completed
First Posted : January 28, 2015
Last Update Posted : May 11, 2017
University of Cape Town
Medecins Sans Frontieres, Netherlands
French Development Agency
UBS Optimus Foundation
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Acquired Immunodeficiency Syndrome Tuberculosis Drug: lopinavir with ritonavir in 1:1 ratio Drug: Lopinavir/ritonavir 4:1 Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 96 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pharmacokinetics Study Comparing Lopinavir Plasma Exposure When Given as Lopinavir/Ritonavir (1:1) in the Presence of Rifampicin and Lopinavir/Ritonavir (4:1) Without Rifampicin in HIV and TB Co-infected Children in South Africa.
Study Start Date : January 2013
Primary Completion Date : December 2016
Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arm Intervention/treatment
Experimental: TB/HIV co-infection
Superboosting lopinavir with ritonavir in 1:1 ratio during TB/HIV co-infection and treatment of HIV with lopinavir/ritonavir 4:1
Drug: lopinavir with ritonavir in 1:1 ratio
During co-treatment of rifampicin containing tuberculosis treatment and lopinavir/ritonavir (4:1) based therapy, additional ritonavir is given to make lopinavir/ritonavir 1:1 ratio
Other Names:
  • Lopinavir/ritonavir
  • Ritonavir
Drug: Lopinavir/ritonavir 4:1
This is the conventional dosing of LPV/r 4:1 for HIV when TB treatment has not been started or has been stopped
Other Name: Lopinavir/ritonavir

Primary Outcome Measures :
  1. Modelled C0/morning trough [ Time Frame: Predose ]
    Proportions of children treated with modelled lopinavir morning C0/morning trough <1mg/L at each of the intensive PK evaluations.

Secondary Outcome Measures :
  1. C0/morning trough [ Time Frame: Predose ]
    Proportions of children with observed lopinavir morning trough, C0/morning trough <1mg/L at each of the intensive PK evaluations

  2. ALT [ Time Frame: baseline, PK1, PK2, PK3 ]
    Safety and tolerability of superboosting focusing on liver functions through clinical and biochemical monitoring.

  3. ECG [ Time Frame: 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

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02348177

South Africa
The Children's Infectious Disease Clinical Research Unit; University of Stellenbosch
Cape Town, Western Cape, South Africa, 7505
Enhancing Care Foundation; Wendworth Hospital
Durban, South Africa, 4013
Perinatal HIV Research Unit
Johannesburg, South Africa, 1864
Shandukani Research WRHI
Johannesburg, South Africa, 2001
Empilweni Services and Research Unit
Johannesburg, South Africa, 2093
Sponsors and Collaborators
Drugs for Neglected Diseases
University of Cape Town
Medecins Sans Frontieres, Netherlands
French Development Agency
UBS Optimus Foundation
Principal Investigator: Mark Cotton, Professor University of Stellenbosch

Additional Information:

Responsible Party: Drugs for Neglected Diseases Identifier: NCT02348177     History of Changes
Other Study ID Numbers: DNDiHIVPed001
First Posted: January 28, 2015    Key Record Dates
Last Update Posted: May 11, 2017
Last Verified: May 2017

Keywords provided by Drugs for Neglected Diseases:
Human immunideficiency virus
lopinavir/ritonavir 1:1
Pediatric TB/HIV co-infection

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antibiotics, Antitubercular