Optimizing Antiretroviral Therapy in HIV-Infected Children and Adolescents

NCT00207948 | Terminated DMC

• 1 other identifier: 1K12RR017613-03
• Study Type: observational
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This was a feasibility study aimed at elevating protease inhibitors (PI) dosage as a part of active antiretroviral therapy (HAART). After the pharmacokinetics for the currently prescribed PI were determined,patients with a vIQ\<1 were eligible for a 50% dose increase for an 8 week time frame after which their vIQ would be reassessed to determine if increasing their PI dosage thereby increasing the bioavaiability would reduce their viral load.

Conditions

HIV Infections

Keywords

Human Immunodeficiency Virus; Protease Inhibitors; Pharmacogenetics; Genes, MDR1, Cytochrome P-450 enzymes; Pharmacokinetics; Pediatrics; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• evaluation of vIQ

  vIQ would be reassessed to determine if increasing their PI dosage thereby increasing the bioavaiability would reduce their viral load.

  8 weeks

Study Arms (1)

Therapeutic Dose Adjustment

To adjust the doses of medications to meet target therapeutic concentrations

Drug: Dose adjustment of Kaletra

Interventions

Dose adjustment of Kaletra DRUG

Adjust the dose by up to +50% of reccomended dosa off the drug to meet target therapeutic concentrations

Also known as: Lopinavir, Ritonavir

Therapeutic Dose Adjustment

Eligibility Criteria

• Age: 4 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The total number of recruited subjects in a previous the study was 78 with 50 subjects on LPV/RTV based ART. Based on PK analysis 4 patients fit inclusion criteria for a dose adjustment feasibility pilot (this study)

You may qualify if:

• Evidence of HIV infection confirmed by positive culture or PCR on at least two occasions, or a positive ELISA and a confirmatory Western Blot. At least one of these tests must be done in an ACTG certified laboratory which is approved to perform the assay for protocol testing
• Age 4-21 years
• Current use of HAART regimen (NRTI or/and NNRTI based) containing a PI
• HIV-RNA levels above 1,000 copies/mL (Stage II)
• vIQ\<1 for Kaletra
• Signed informed consent and, if indicated, signed informed assent or waiver of assent.

You may not qualify if:

• Grade 3-4 DAIDS defined toxicity
• Use of cimetidine (used as the internal standard for the HPLC-MS/MS assay)
• Any active opportunistic infection
• Any of the following laboratory findings at entry: absolute neutrophil count \<750 cells/mm3; platelet count \<75,000 cells/mm3; AST \>3 times upper limit of age adjusted normal values; ALT \>3 times upper limit of age adjusted normal values; serum creatinine \>1.2mg/dL.
• Patients on dual PI regimen (except when second PI is given for boosting) at the time of enrollment

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (3)

• Rakhmanina N, van den Anker J, Baghdassarian A, Soldin S, Williams K, Neely MN. Population pharmacokinetics of lopinavir predict suboptimal therapeutic concentrations in treatment-experienced human immunodeficiency virus-infected children. Antimicrob Agents Chemother. 2009 Jun;53(6):2532-8. doi: 10.1128/AAC.01374-08. Epub 2009 Mar 2.

  PMID: 19258274 RESULT

• Neely MN, Rakhmanina NY. Comment on: Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother. 2010 Apr;65(4):808-9; author reply 809-10. doi: 10.1093/jac/dkp489. Epub 2010 Jan 19. No abstract available.

  PMID: 20086000 RESULT

• Rakhmanina NY, Neely MN, Van Schaik RH, Gordish-Dressman HA, Williams KD, Soldin SJ, van den Anker JN. CYP3A5, ABCB1, and SLCO1B1 polymorphisms and pharmacokinetics and virologic outcome of lopinavir/ritonavir in HIV-infected children. Ther Drug Monit. 2011 Aug;33(4):417-24. doi: 10.1097/FTD.0b013e318225384f.

  PMID: 21743379 RESULT

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Lopinavir; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• Natella Y Rakhmanina, MD

  Children's National Medical Center, Children's Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 21, 2005
• Study Start: November 1, 2004
• Primary Completion: May 1, 2009
• Study Completion: July 1, 2009
• Last Updated: August 5, 2015

Record last verified: 2015-08

Locations

US (1)