A Pilot Study of the Immunologic Reconstitution in HIV-1 Infected Children Receiving Highly Active Antiretroviral Therapy With Combination Ritonavir, Nevirapine and Stavudine

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001688
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: November 2001
  Purpose

This is a pilot study to evaluate the ability of highly active antiretroviral therapy administered to children with HIV-1 infection to effect immunoreconstitution in children with HIV-1 infection. In addition, this study will determine the safety of combination therapy with ritonavir, nevirapine and stavudine (d4T) as well as the anti-HIV activity of combination therapy with ritonavir, nevirapine and stavudine. A total of 25 HIV-1 infected children will be studied, including both moderately and severely immunocompromised individuals. The children will be treated with ritonavir, nevirapine and stavudine or with predefined drug substitutions in the case of intolerance. Immunoreconstitution, defined as the repopulation of naive T cells, will be studied by determining the presence and extent of production of new naive (thymic derived) CD4+ T cells and their T cell receptor repertoire. Drug pharmacokinetic profiles in this regimen will be examined.


Condition Intervention Phase
HIV Infection
Drug: Ritonavir
Drug: Nevirapine
Drug: Stavudine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: A Pilot Study of the Immunologic Reconstitution in HIV-1 Infected Children Receiving Highly Active Antiretroviral Therapy With Combination Ritonavir, Nevirapine and Stavudine

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 25
Study Start Date: January 1998
Estimated Study Completion Date: November 2001
Detailed Description:

This is a pilot study to evaluate the ability of highly active antiretroviral therapy administered to children with HIV-1 infection to effect immunoreconstitution in children with HIV-1 infection. In addition, this study will determine the safety of combination therapy with ritonavir, nevirapine and stavudine (d4T) as well as the anti-HIV activity of combination therapy with ritonavir, nevirapine and stavudine. A total of 25 HIV-1 infected children will be studied, including both moderately and severely immunocompromised individuals. The children will be treated with ritonavir, nevirapine and stavudine or with predefined drug substitutions in the case of intolerance. Immunoreconstitution, defined as the repopulation of naive T cells, will be studied by determining the presence and extent of production of new naive (thymic derived) CD4+ T cells and their T cell receptor repertoire. Drug pharmacokinetic profiles in this regimen will be examined.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Children between ages of 4 years and 18 years.

Diagnosis of HIV-1 infection as defined by the Centers for Disease Control (CDC) Definition.

Availability of a parent or guardian to provide Informed Consent.

Child is not critically ill or clinically unstable.

No CDC categories N1 and A1 (1994 revised classification for HIV infection in children less than 13 years of age) and the CDC 1993 revised HIV classification and expanded AIDS surveillance definition for adolescents and adults.

Non-presence of an active opportunistic infection requiring acute intervention at the time of entry (e.g. CMV, aspergillosis, cryptococcosis, Candida, etc.). Patients receiving treatment for an infection that requires prolonged treatment must have been stable on therapy for at least 30 days prior to study entry.

No administration of chemotherapeutic agents, investigational agents or use of immunomodulating agents such as IVIG, corticosteroids, interferons, pentoxifylline, G-CSF/GM-CSF, erythropoeitin, growth hormone and other growth factors within one month of enrollment.

None of the following laboratory abnormalities within 2 weeks of study entry:

Total WBC count less than 1500/mm(3) or an absolute neutrophil count less than 750/mm(3);

Hemoglobin less than 8.0 g/dl;

Platelet count less than 75,000/mm(3);

Creatinine greater than 2.0 x normal;

Creatinine clearance less than or equal to 50 mL/min/m(2);

Total bilirubin greater than 2 x normal;

SGOT/SGPT greater than 5 x normal;

Serum amylase pancreatic isoenzyme greater than 90 U/L (2 x upper limit of normal for adult). Serum amylase pancreatic isoenzyme should be obtained only if total serum amylase is greater than 180 U/L.

No history of clinical pancreatitis and/or elevation in serum amylase pancreatic isoenzyme of greater than 180 U/L.

No history of peripheral neuropathy of Grade II or greater severity.

No previous treatment with ritonavir, indinavir, nelfinavir, nevirapine or stavudine. Patients may have received treatment with ritonavir, indinavir, nelfinavir for less than 4 weeks.

Ability to swallow tablets.

No child for whom the volume of research blood required for study evaluation exceeds the maximum volume of research blood allowable (3 ml/kg in a single blood withdrawal and 7 ml/kg in a 6-week period). This would be applicable to a child less than 16.5 kg.

No patients who refuse or cannot have leukapheresis done.

Sexually active post-menarchal females must be willing to use a barrier method of contraception or be willing to remain sexually abstinent.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001688

Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001688     History of Changes
Other Study ID Numbers: 980041, 98-C-0041
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
CD4 Cells
Cytokines
Anti-Retroviral Activity
V Beta Repertoire
CD-4-Naive T Cells
CD-4-Memory T Cells

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Nevirapine
Ritonavir
Stavudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014