A Pilot Study of the Immunologic Reconstitution in HIV-1 Infected Children Receiving Highly Active Antiretroviral Therapy With Combination Ritonavir, Nevirapine and Stavudine
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infection
Intervention: Ritonavir (Drug); Nevirapine (Drug); Stavudine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Cancer Institute (NCI)
Summary
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.
Clinical Details
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
Study design: Treatment, Safety/Efficacy Study
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
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
National Cancer Institute (NCI), Bethesda, Maryland 20892, United States
Additional Information
Related publications: Yarchoan R, Mitsuya H, Broder S. Challenges in the therapy of HIV infection. Immunol Today. 1993 Jun;14(6):303-9. Review. Mackall CL, Granger L, Sheard MA, Cepeda R, Gress RE. T-cell regeneration after bone marrow transplantation: differential CD45 isoform expression on thymic-derived versus thymic-independent progeny. Blood. 1993 Oct 15;82(8):2585-94. Mackall CL, Fleisher TA, Brown MR, Andrich MP, Chen CC, Feuerstein IM, Horowitz ME, Magrath IT, Shad AT, Steinberg SM, et al. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med. 1995 Jan 19;332(3):143-9.
Starting date: January 1998
Ending date: November 2001
Last updated: March 3, 2008
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