A Phase I /II Study of the Protease Inhibitor Indinavir (MK-0639) in Children With HIV Infection

Inclusion Criteria

Age - six months to 18 years.

PREVIOUSLY UNTREATED OR MINIMALLY TREATED PATIENTS:

Asymptomatic HIV-infected children with an age-corrected absolute CD4 count that renders
them at possible risk for an AIDS-related opportunistic infection, or;

Children with moderate to severe symptomatic HIV infection as defined by the CDC
classification.

Absence of active opportunistic infection requiring acute intervention at the time of
entry.

Prophylaxis for PCP with trimethoprim/sulfamethoxazole or pentamidine at the time of entry
will be allowed.

Availability of a parent or legal guardian to give informed consent and who is deemed
sufficiently reliable to return for the child's follow-up visits.

PREVIOUSLY TREATED PATIENTS WITH REFRACTORY DISEASE OR INTOLERANCE TO PRIOR THERAPY:

HIV-infected patients who have been previously treated with one or more dideoxynucleosides
(zidovudine, didanosine, lamivudine, stavudine, zalcitabine) or another protease inhibitor
(will be analysed separately) and have experienced either a withdrawal grade toxicity or
refractory disease evidenced by progressive clinical immunological deterioration.

Availability of a parent or legal guardian to give informed consent and who is deemed
sufficiently reliable to return for the child's follow-up visits.

ALL CHILDREN:

Must not be critically ill or clinically unstable.

Patients receiving treatment for an acute infection must have been on stable therapy for
at least 7 days prior to entry on study.

MUST NOT HAVE ONE OR MORE OF THE FOLLOWING LABORATORY FINDINGS (WITHIN 2 WEEKS OF ENTRY
AND NOT YET RESOLVED):

Total WBC count less than 1500 cells/mm(3).

Neutrophil plus band count less than 750 cells/mm(3).

Hemoglobin less than 8.0 g/dl (history of recent transfusion is not an exclusion).

Platelet count less than 500,000/mm(3).

Creatinine greater than 2 times the upper limit of normal.

Liver transaminase greater than 3 times the upper limit of normal.

Bilirubin greater than 1.5 mg/dL.

Hematuria.

Because of the possibility for an increased risk of kidney stone formation patients must
not have severe recurrent or persistent diarrhea, or a family history of kidney stones.

Patients must not have received, within 30 days prior to entry, therapy with
immunomodulating agents (interleukin-2, interferons, growth hormone, IGF-1, or other
biological response modifier), cytolytic chemotherapeutic agents, radiation therapy.

Stable (e.g., for greater than 4 weeks prior to entry) corticosteroids therapy for the
treatment of lymphocytic interstitial pneumonitis or an autoimmune process or stable
therapy with G-CSF (Neupogen) at the same dosage for at least 4 weeks are acceptable.

Must not have an active opportunistic infection requiring acute intervention.

Women must not be pregnant or breast feeding.