This study will continue to follow children who participated in an earlier National Cancer
Institute trial of HIV treatment with a protease inhibitor. Children in this study will
receive a combination of at least three drugs that include at least one protease inhibitor
and one reverse transcriptase inhibitor.
The study will examine to what extent these drugs can restore immune function in
HIV-infected children and over what length of time. It will look at changes in the amounts
of virus and the specific types of immune cells in the body over the 96-week trial period.
It will also examine patients' immune system response to influenza and tetanus vaccinations.
The children will either continue to receive the anti-HIV drugs they have been taking, or
their medicines will be changed to a different combination of protease inhibitor and reverse
transcriptase inhibitor. Before and during the study, patients will undergo various tests,
including a physical examination, blood tests and chest X ray, immune response tests, CT
scan, eye examination, electrocardiogram and echocardiogram. A procedure called apheresis
may be done to collect white blood cells. In this procedure, whole blood is drawn similar to
donating blood, the white cells are separated out by a machine, and the red cells are
returned to the body.
This study will evaluate the extent of immunoreconstitution in children receiving
combination antiretroviral therapy that includes a protease inhibitor and reverse
transcriptase inhibitors. The children who will be evaluated and followed in this study are
those who have previously been studied on other protease inhibitor-containing anti-HIV
protocols within the HIV and AIDS Malignancy Branch. This study will provide a mechanism to
assess the long-term immunologic changes of potent combination therapy in this unique
population and to relate this to the virologic changes. A total of 50 HIV-1 infected
children will be studied. The children enrolled in this protocol will either continue their
current combination of protease inhibitor and reverse transcriptase therapy or, if deemed
clinically appropriate, will be changed to a new, best available combination of protease
inhibitor and reverse transcriptase inhibitors. Long-term immunoreconstitution, defined as
the repopulation of naive CD4+T lymphocytes, will be studied by determining the presence and
extent of production of new naive (thymic derived) CD4+T cells and by the ability of
patients to mount new helper T cell responses after immunization with influenza and tetanus
toxoid. Expansion of T cell receptor will also be explored in subsets of enrolled patients.
In addition, unforeseen toxicities attributable to the use of combination antiretroviral
therapy have been recognized and described in adult patients. This study will evaluate
abnormalities in lipid and glucose metabolism, changes in the distribution of body fat, and
surrogate markers of cardiovascular disease risk in this cohort of pediatric patients.
Age greater than 1 year and less than 21 years.
Diagnosis of HIV-1 infection as defined by the Centers for Disease Control (CDC).
Currently on at least a three drug combination that includes a protease inhibitor (PI) and
reverse transcriptase inhibitor (RTI) therapy for at least 6 months.
Patient must have received initial protease inhibitor treatment in studies in the HIV and
AIDS Malignancy Branch but need not be enrolled on another NIH study to be eligible for
Age-adjusted CD4+ T lymphocytes greater than 200 cells/ml.
Measurements of CD4+45RA+ and CD4+45RO+ T lymphocytes taken within 9 weeks of the time of
initiation of protease-inhibitor therapy.
Availability of a parent or guardian to provide informed consent.
Critically ill or clinically unstable child.
Patients receiving treatment for an infection that requires prolonged treatment must have
been stable on therapy for at least 14 days prior to study entry.
Administration of chemotherapeutic agents or use of immunomodulating agents such as high
dose corticosteroids, interferons, pentoxifylline, G-CSF/GM-CSF, erythropoietin, growth
hormone and other growth factors within one month of enrollment. However, patients on
anti-inflammatory drugs or stable doses of immunoglobulins (including hyperimmune
immunoglobulin) will be eligible unless the latter are directed at a T-cell specific
Sexually active post-menarchal female unwilling to use a barrier method of contraception
or unwilling to remain sexually abstinent.
Patients who, in the opinion of the Protocol Chairperson or Principal Investigator:
may not be likely to benefit from this study,
may be put at undue risk by participation in this study,
are unlikely to comply with the study requirements.