Lopinavir/Ritonavir Monotherapy in Children

Study Overview
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Brief Summary
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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).

Detailed Description
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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: A decrease in total cholesterol, LDL and triglycerides An improvement in quality of life and in adherence to ARVs No change in viral load

Official Title
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Simplifying Antiretroviral Treatment in Virally Suppressed Children by Switching From Double Boosted Protease Inhibitors to Lopinavir/Ritonavir Monotherapy

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: LPV/r


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infected children ages 2 to 18 years Treated with double boosted PIs during the last three months Two consecutive plasma HIV-RNA levels < 50 copies/ml at least 3 months apart Willing to restart HAART with the same regimen as before enrollment, when indicated Signed written informed consent Exclusion Criteria: Active AIDS-defining disease at screening Pregnancy

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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efficacy, safety, pharmacokinetics, LPV/r monotherapy, Thai children, efficacy safety LPV/r monotherapy maintenance, treatment experienced