Anti-HIV Drug Regimens With or Without Protease Inhibitors and Drug Level Monitoring in HIV Infected Adolescents

NCT ID: NCT00075907

Last Updated: 2013-10-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-07-31

Study Completion Date

2006-09-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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HIV Infections

Keywords

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Acute Infection Treatment Experienced Treatment Naive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Efavirenz + 2 NRTIs

Intervention Type DRUG

Lopinavir/Ritonavir + 2 NRTIs

Intervention Type DRUG

Therapeutic Drug Monitoring

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

13 Years

Maximum Eligible Age

23 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Margarita Silio, MD

Role: STUDY_CHAIR

Tulane Medical Center

Russell Van Dyke, MD

Role: STUDY_CHAIR

Tulane Medical Center

Locations

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Usc La Nichd Crs

Alhambra, California, United States

Site Status

Long Beach Memorial Med. Ctr., Miller Children's Hosp.

Long Beach, California, United States

Site Status

Children's Hospital of Los Angeles NICHD CRS

Los Angeles, California, United States

Site Status

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, United States

Site Status

Chicago Children's CRS

Chicago, Illinois, United States

Site Status

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, United States

Site Status

Children's Hosp.

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases

Baltimore, Maryland, United States

Site Status

SUNY Stony Brook NICHD CRS

Stony Brook, New York, United States

Site Status

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, United States

Site Status

St. Jude/UTHSC CRS

Memphis, Tennessee, United States

Site Status

Children's Med. Ctr. Dallas

Dallas, Texas, United States

Site Status

Texas Children's Hosp. CRS

Houston, Texas, United States

Site Status

Countries

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Puerto Rico United States

References

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Eron JJ, Feinberg J, Kessler HA, Horowitz HW, Witt MD, Carpio FF, Wheeler DA, Ruane P, Mildvan D, Yangco BG, Bertz R, Bernstein B, King MS, Sun E. Once-daily versus twice-daily lopinavir/ritonavir in antiretroviral-naive HIV-positive patients: a 48-week randomized clinical trial. J Infect Dis. 2004 Jan 15;189(2):265-72. doi: 10.1086/380799. Epub 2004 Jan 7.

Reference Type BACKGROUND
PMID: 14722892 (View on PubMed)

Deschamps AE, Graeve VD, van Wijngaerden E, De Saar V, Vandamme AM, van Vaerenbergh K, Ceunen H, Bobbaers H, Peetermans WE, de Vleeschouwer PJ, de Geest S. Prevalence and correlates of nonadherence to antiretroviral therapy in a population of HIV patients using Medication Event Monitoring System. AIDS Patient Care STDS. 2004 Nov;18(11):644-57. doi: 10.1089/apc.2004.18.644.

Reference Type BACKGROUND
PMID: 15633262 (View on PubMed)

Murphy DA, Sarr M, Durako SJ, Moscicki AB, Wilson CM, Muenz LR; Adolescent Medicine HIV/AIDS Research Network. Barriers to HAART adherence among human immunodeficiency virus-infected adolescents. Arch Pediatr Adolesc Med. 2003 Mar;157(3):249-55. doi: 10.1001/archpedi.157.3.249.

Reference Type BACKGROUND
PMID: 12622674 (View on PubMed)

Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, Squier C, Wagener MM, Singh N. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000 Jul 4;133(1):21-30. doi: 10.7326/0003-4819-133-1-200007040-00004.

Reference Type BACKGROUND
PMID: 10877736 (View on PubMed)

Van Dyke RB, Lee S, Johnson GM, Wiznia A, Mohan K, Stanley K, Morse EV, Krogstad PA, Nachman S; Pediatric AIDS Clinical Trials Group Adherence Subcommittee Pediatric AIDS Clinical Trials Group 377 Study Team. Reported adherence as a determinant of response to highly active antiretroviral therapy in children who have human immunodeficiency virus infection. Pediatrics. 2002 Apr;109(4):e61. doi: 10.1542/peds.109.4.e61.

Reference Type BACKGROUND
PMID: 11927734 (View on PubMed)

Related Links

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http://clinicaltrials.gov/ct/show/NCT00039741

Click here for more information about PACTG 390

http://clinicaltrials.gov/ct/show/NCT00006304

Click here for more information about PACTG 219C

Other Identifiers

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DAIDS-ES ID 10043

Identifier Type: -

Identifier Source: secondary_id

PACTG P1034

Identifier Type: -

Identifier Source: org_study_id