Anti-HIV Drug Regimens With or Without Protease Inhibitors and Drug Level Monitoring in HIV Infected Adolescents
Summary
The purpose of this study is to compare the effectiveness of anti-HIV drug regimens with or without a protease inhibitor (PI) in HIV infected adolescents. It will also determine if monitoring drug levels and adjusting the dose as necessary improves the effectiveness of these regimens.
Description
HIV infected adolescents may have a significantly higher capacity for immune reconstitution following highly active antiretroviral therapy (HAART), compared to adults. Despite this advantage, HIV infected adolescents are often reluctant to get proper medical care, follow through with doctor appointments, and adhere to medication schedules and regimens necessary to keep their infection under control. Lopinavir/ritonavir (LPV/r), a PI, and efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), both have long half-lives that make them ideal drugs for the adolescent population, as they are more forgiving if patients miss or sleep through doses. The availability of once-daily dosing of LPV/r will reduce pill burden and offers more flexibility in medication scheduling, also helping to promote treatment adherence among this age group. This study will examine the effectiveness of two HAART regimens, one with the PI LPV/r and two nucleoside reverse transcriptase inhibitors (NRTIs), and the other with the NNRTI EFV and two NRTIs. The efficacy of therapeutic drug monitoring (TDM) and subsequent dose adjustment will also be assessed with both regimens.
Patients will be enrolled in this study for 96 weeks and will be randomly assigned into one of two groups. Group 1 will receive LPV/r and 2 NRTIs. Treatment naive patients in Group 1 will have the option of receiving either once-daily dosing or twice-daily dosing of LPV/r. Treatment experienced patients will receive twice-daily dosing of LPV/r. Patients on once-daily dosing of LPV/r who become intolerant to the regimen will be permitted to switch to twice-daily dosing. Group 2 will receive EFV and 2 NRTIs. All patients will be independently and simultaneously randomly assigned to undergo either TDM with subsequent dose adjustment if necessary or no TDM.
Patient medical history and physical exam will be conducted at screening, entry, Weeks 2, 4, 8, every 8 weeks until Week 48, and every 12 weeks thereafter. Blood collection will occur at all study visits. Self-reported pill counts and MEMS TrackCap readings (on LPV/r and EFV bottles) will be noted at most visits. Patients will be asked to complete adherence questionnaires at selected study visits.
Patients enrolled in PACTG 390 (Different Combination Regimens and Treatment-Switching Guidelines in HIV Infected Children 18 Years of Age and Younger) are encouraged to coenroll simultaneously in this study and in PACTG 219C (Long-Term Effects of HIV Exposure and Infection in Children).
Study Design
Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
HIV Infections
Intervention
Efavirenz + 2 NRTIs, Lopinavir/Ritonavir + 2 NRTIs, Therapeutic Drug Monitoring
Location
Phoenix Children's Hospital
Phoenix
Arizona
United States
85006
Status
Completed
Source
National Institute of Allergy and Infectious Diseases (NIAID)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00075907
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Biomarkers, Pharmacological
Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING).
Fetal Monitoring
Physiologic or biochemical monitoring of the fetus. It is usually done during LABOR, OBSTETRIC and may be performed in conjunction with the monitoring of uterine activity. It may also be performed prenatally as when the mother is undergoing surgery.
Ritonavir
An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV.
Drug Monitoring
The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.
Drug Carriers
Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
Clinical Trials
The purpose of this study was to compare the safety and tolerability of the to-be-marketed lopinavir/ritonavir (LPV/r) tablet formulation with the marketed soft gel capsule (SGC) formulati...
The purpose of this study was to compare the safety, tolerability, and antiviral activity of once-daily (QD) and twice-daily (BID) dosing of the lopinavir/ritonavir (LPV/r) tablet formulat...
A study comparing Indinavir plus Ritonavir plus 2 NRTIs vs. Nelfinavir 1250 plus two nucleoside reverse transcriptase inhibitors (NRTIs) in the treatment of HIV positive patients who have...
This study will compare an anti-HIV drug combination of protease inhibitor plus a nonnucleoside reverse transcriptase inhibitor (NNRTI) to one that includes three nucleoside reverse transc...
A Comparison of Two Anti-HIV Drug Regimens for Youth Who Have Failed Prior Therapy
HIV infected children and adolescents who have taken many anti-HIV drugs may have limited treatment options and are at high risk for progressing to AIDS. The purpose of this study is to de...
PubMed Articles
BACKGROUND: The role of exposure to specific antiretroviral drugs on risk of myocardial infarction in human immunodeficiency virus (HIV)-infected patients is debated in the literature. METHODS: To ass...
Antiretroviral release from poly(DL-lactide-co-glycolide) nanoparticles in mice.
Objectives Free ritonavir, lopinavir and efavirenz injected intraperitoneally were compared with antiretroviral (AR) nanoparticles (NPs). Methods This is a prospective study in BALB/c mice comparing t...
Nucleoside reverse transcriptase inhibitors (NRTIs) are a key class of drugs for the treatment of HIV infection. NRTIs are intracellularly phosphorylated to their active triphosphate metabolites and c...
OBJECTIVES: Rifampicin profoundly reduces lopinavir concentrations. Doubled doses of lopinavir/ritonavir compensate for the effect of rifampicin in adults, but fail to provide adequate lopinavir conce...
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Doubling the dose of lopinavir/ritonavir overcomes the effect of rifampicin on lopinavir concentrations. However, lopinavir concentrations are highly variable...
