A Comparative Trial of Protease-Containing and Protease-Sparing HAART Regimens in HIV-Infected Adolescents With an Evaluation of Therapeutic Drug Monitoring
Data Collection
Blood-Borne Infections+11
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
Summary
Study start date: July 1, 2004
Actual date on which the first participant was enrolled.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).
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.240 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 13 to 23 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: * HIV infected * HIV RNA viral load of 10,000 copies/ml or more at screening * Weigh 35 kg (77.2 lbs) or more * HAART naive or received a single regimen of combination therapy consisting of NRTIs with or without a single PI (except LPV). Patients who received zidovudine monotherapy during pregnancy or used low-dose ritonavir (RTV) as a PI boost are not excluded. * For PI experienced patients, have sensitivity to LPV at screening * Able to receive, as part of background HAART chosen by their physician, at least one new NRTI that is likely to be active against the patient's virus and unlikely to have cross-resistance with previously used NRTIs * Willing to use acceptable forms of contraception * Parent or legal guardian willing to provide informed consent, if applicable Exclusion Criteria: * Prior receipt of any NNRTI or LPV * Require certain medications * Grade 3 or 4 clinical or laboratory toxicity, as defined by the Division of AIDS Toxicity Table for Grading Severity of Pediatric Adverse Effects * Chemotherapy for active malignancy * Acute opportunistic or serious bacterial infection requiring therapy at study entry * Investigational treatment within 30 days of study entry * Score of 20 or more on Beck Depression Inventory (BDI-II) or suicidal thoughts on BDI-II (score of 2 or 3 on Question 9), regardless of total score * Pregnant within 48 hours of starting EFV * Breastfeeding
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.Study Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 13 locations
Long Beach Memorial Med. Ctr., Miller Children's Hosp.
Long Beach, United StatesChildren's Hospital of Los Angeles NICHD CRS
Los Angeles, United StatesUniv. of Colorado Denver NICHD CRS
Aurora, United States