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Lopinavir/Ritonavir Monotherapy in Children

This study has been completed.
Sponsor:
Collaborators:
Chulalongkorn University
Khon Kaen University
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT00626301
First received: February 21, 2008
Last updated: June 4, 2010
Last verified: June 2010
History of Changes
  Purpose

The purpose of this study is to evaluate the efficacy (clinical, immunological, virological outcome), pharmacokinetics and safety of lopinavir/ritonavir (LPV/r) monotherapy maintenance in Thai children after viral load suppression with double boosted protease inhibitors (PIs).


Condition Intervention Phase
HIV Infections
 Drug: LPV/r
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Simplifying Antiretroviral Treatment in Virally Suppressed Children by Switching From Double Boosted Protease Inhibitors to Lopinavir/Ritonavir Monotherapy

Resource links provided by NLM:

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

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Primary Outcome Measures:
  • To evaluate efficacy (clinical, immunological, virological outcome), pharmacokinetics and safety of LPV/r monotherapy maintenance in Thai children after viral load suppression with double boosted PIs [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Estimated Enrollment: 40
Study Start Date: November 2007
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Children who have completed HIV-NAT 017. Children treated with other double boosted PIs such as indinavir plus lopinavir/ ritonavir are also included.
 Drug: LPV/r
LPV/r 230/57.5 mg/m2 orally q12h or the adjusted dose based on therapeutic drug monitoring of LPV/r prior to enrollment as maintenance monotherapy

Detailed Description:

The commonly used antiretroviral (ARV) regimen in the Thai National Access to Antiretroviral Program for People Living with HIV/AIDS is non-nucleoside reverse transcriptase (NNRTI) based HAART. However, one of the most challenging concerns of antiretroviral therapy is the emergence of drug resistance mutants which occurs in 30-40% of treated patients. Children failing nucleoside reverse transcriptase inhibitor (NRTI)/NNRTI regimens have limited options for second line therapy especially in a developing country such as Thailand.

At HIV-NAT, the Thai Red Cross AIDS Research Centre, we had a trial using standard doses of double boosted PIs, Lopinavir/ritonavir and Saquinavir, HIV-NAT 017, in 50 HIV infected children who failed the first line regimen. This ongoing trial showed the good efficacy of the double boosted PI in children, significant increasing of CD4 and decreasing of HIV-RNA in children who adhered to the treatment. However, a high number of pill counts for this regimen, 5-8 pills every 12 hours, life long can affect adherence and treatment outcome. In the HIV-NAT 017 study, a 48 week intent to treat analysis, 38% and 50% of children had total cholesterol ≥ 200 mg/dl and triglycerides ≥ 150 mg/dl after double boosted PI. Those lipid levels were significantly elevated when compared to baseline (p < 0.001). Double boosted PIs are also very costly. Studies in adults have shown that double boosted PIs had a disadvantage in lipid effect compared to a single PI-based regimen.

Lopinavir/ritonavir, the only PI co-formulated with ritonavir, is recommended as a first-line option for antiretroviral-naive patients initiating PI-based therapy and has shown a high potency, efficacy, and safety in HIV patients with high genetic barriers to resistance. LPV/r has also shown excellent efficacy in ARV-experienced children.

Mono boosted PI therapy trials in HIV adults, as the maintenance therapy after suppressed viral load, have been shown to be effective and safe. This strategy not only decreases the number of pills per dose but also saves for ARV cost and might improve the patient's adherence. As maintenance monotherapy after HIV-1 viral suppression, lopinavir/ritonavir has shown efficacy in adult trials with 80-90% virological suppression. A pilot study of a switch to lopinavir/ritonavir (LPV/r) monotherapy from nonnucleoside reverse transcriptase inhibitor-based therapy was reported with 92% of the participants on treatment at week 48 having HIV RNA < 75 copies/mL.

Therefore, in this trial, we aim to see the efficacy and safety of lopinavir/ritonavir maintenance monotherapy in Thai HIV infected children after virological suppression from previous double boosted PIs.

By simplifying maintenance antiretroviral treatment in children who are virally suppressed from previous double boosted PIs to lopinavir/ritonavir monotherapy, we hope to achieve the following:

  1. A decrease in total cholesterol, LDL and triglycerides
  2. An improvement in quality of life and in adherence to ARVs
  3. No change in viral load
  Eligibility
Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV infected children ages 2 to 18 years
  2. Treated with double boosted PIs during the last three months
  3. Two consecutive plasma HIV-RNA levels < 50 copies/ml at least 3 months apart
  4. Willing to restart HAART with the same regimen as before enrollment, when indicated
  5. Signed written informed consent

Exclusion Criteria:

  1. Active AIDS-defining disease at screening
  2. Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00626301

Locations
Thailand
Department of Pediatrics, Chulalongkorn University Hospital
Bangkok, Thailand, 10330
HIV-NAT
Bangkok, Thailand, 10330
Department of Pediatrics, Khon Kaen University
Khon Kaen, Thailand
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
Chulalongkorn University
Khon Kaen University
  More Information

Additional Information:
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Prof. Praphan Phanuphak and Dr. Pope Kosalaraksa, HIV-NAT and Khon Kaen University
ClinicalTrials.gov Identifier: NCT00626301     History of Changes
Other Study ID Numbers: HIV-NAT 077, IRB# 241/50
Study First Received: February 21, 2008
Last Updated: June 4, 2010
Health Authority: Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
efficacy
safety
pharmacokinetics
LPV/r monotherapy
 Thai children
efficacy safety LPV/r monotherapy maintenance
treatment experienced

Additional relevant MeSH terms:
Lopinavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
 HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015