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