Phase I Study to Evaluate the Safety and Immunogenicity of HIV-1 Immunogen in Children With HIV-1 Infection
Phase I Study to Evaluate the Safety and Immunogenicity of HIV-1 Immunogen in Children With HIV-1 Infection
This is a single dose, phase I study to evaluate the safety/tolerance and the immunogenicity
 of HIV-1 Immunogen, gp120-depleted inactivated HIV-1 preparation in Incomplete Freund's
 Adjuvant (IFA), in children with HIV-1 infection. A total of 32 children with HIV-1 infection
 will be enrolled in the study. Arm A of the study will enroll children who have no or
 moderate immune suppression at the time of study entry as defined by CDC classification and
 who have no history of and do not require antiretroviral therapy. Antiretroviral treatment
 given for less than 7 weeks (up to 6 weeks and 6 days) prior to entry will be considered as
 "no history" of treatment (treatment naive). Arm B will enroll children who have no or
 moderate immune suppression at the time of study entry as defined by CDC classification and
 who are on or have received antiretroviral treatment for more than 7 weeks. In order to
 assess the age-associated impact on the immune response rate, we plan to continue to attempt
 to enroll infants younger than 24 months of age. Children in each arm will receive 10 units
 of HIV-1 Immunogen intramuscularly at 0, 3, 6, 9, and 12 months.

 Antiretroviral treatment will commence once patients meet the criteria for an initiation of
 the treatment as defined in the protocol. All antiretroviral agents that are currently
 approved by FDA for clinical indications in HIV-1-infected children (pediatric labeling) are
 permitted in the protocol. If the child has been receiving a single agent other than ddI, or
 has been on investigational antiretroviral agents, his/her antiretroviral therapy will have
 to be changed to an optimal combination regimen of the approved agents at least 6 weeks prior
 to the enrollment.
This is a single dose, phase I study to evaluate the safety/tolerance and the immunogenicity
 of HIV-1 Immunogen, gp120-depleted inactivated HIV-1 preparation in Incomplete Freund's
 Adjuvant (IFA), in children with HIV-1 infection. A total of 32 children with HIV-1 infection
 will be enrolled in the study. Arm A of the study will enroll children who have no or
 moderate immune suppression at the time of study entry as defined by CDC classification and
 who have no history of and do not require antiretroviral therapy. Antiretroviral treatment
 given for less than 7 weeks (up to 6 weeks and 6 days) prior to entry will be considered as
 "no history" of treatment (treatment naive). Arm B will enroll children who have no or
 moderate immune suppression at the time of study entry as defined by CDC classification and
 who are on or have received antiretroviral treatment for more than 7 weeks. In order to
 assess the age-associated impact on the immune response rate, we plan to continue to attempt
 to enroll infants younger than 24 months of age. Children in each arm will receive 10 units
 of HIV-1 Immunogen intramuscularly at 0, 3, 6, 9, and 12 months.

 Antiretroviral treatment will commence once patients meet the criteria for an initiation of
 the treatment as defined in the protocol. All antiretroviral agents that are currently
 approved by FDA for clinical indications in HIV-1-infected children (pediatric labeling) are
 permitted in the protocol. If the child has been receiving a single agent other than ddI, or
 has been on investigational antiretroviral agents, his/her antiretroviral therapy will have
 to be changed to an optimal combination regimen of the approved agents at least 6 weeks prior
 to the enrollment.
Children between the ages of 3 months and 18 years.

 Diagnosis of HIV-1 infection as defined by the Centers for Disease Control (CDC)
 Definition. Children and adolescents with vertically, transfusion or sexually acquired
 HIV-1 infection are eligible.

 Availability of a parent or guardian to provide Informed Consent.

 ARM A:

 Children and adolescents with vertically, transfusion or sexually acquired HIV-1 infection.

 No or moderate immune suppression at the time of study entry as defined by the CDC
 Classification System, Immune Categories 1 and 2.

 No history of or indication for antiretroviral intervention at time of enrollment or not
 receiving antiretroviral treatment because: (a) the patient has elected to decline
 treatment or (b) in the opinion of the patient's health care provider, antiretroviral
 treatment is not currently recommended because of the patient's inability to adhere to
 therapy, promoting the development of viral resistance.

 Children younger than 24 months of age must not have had plasma HIV-1 RNA levels greater
 than 8 X 10(4) copies/ml previously and at the time of initial evaluation, confirmed at
 least at two different time points 2 to 4 weeks apart, showing no sign of increase
 (increment less than 0.5 log(10). If the child has had plasma HIV-1 RNA levels greater than
 8 X 10(4) copies/ml at some point prior to the initial evaluation, he/she will have to be
 placed on antiretroviral treatment and must meet all the criteria for Arm B.

 ARM B:

 Children and adolescents with vertically, transfusion, or sexually acquired HIV-1
 infection, who are on or have received antiretroviral treatment of longer than 7 weeks.

 No or moderate immune suppression at the time of study entry as defined by CDC
 Classification System, Immune Categories 1 and 2.

 Children younger than 24 months or age, who meet all the inclusion criteria for army B must
 have plasma HIV-1 RNA levels less than 5 X 10(4) copies/ml while receiving optimal
 antiretroviral therapy, confirmed at least two different time points 2 to 4 weeks apart,
 showing no sign of increase (increment less than 0.5 log(10). If the child has been
 previously treated with antiretroviral drugs for more than 7 weeks (therefore not eligible
 for arm A) and is currently off drugs, he/she will have to be placed on optimal
 antiretroviral agents and will have to maintain viral RNA levels below 5 X 10(4) copies/ml
 prior to the entry.

 Each child enrolled in arm B has to be on constant regimen of antiretroviral treatment for
 at least 6 weeks-prior to the first inoculation. Children in immune categories 1 and 2 at
 the time of study entry will be allowed to enroll.

 Not critically ill or clinically unstable or no presence of active infection requiring
 on-going (or induction) therapy.

 No evidence of severe immune suppression at the time of study entry as defined by CDC
 classification system, Immune Category 3.

 For children younger than 24 months of age, no plasma HIV-1 RNA levels greater than or
 equal to 5 x 10(4) copies/ml despite appropriate antiretroviral treatment, confirmed at
 least at two different time points 2 to 4 weeks apart.

 No use of tube feeding or intravenous hyperalimentation itself will be allowed as long as
 it is a stable regimen.

 No administration of chemotherapeutic agents, or use of immunomodulating agents such as
 corticosteroids, interferons, G-CSF, EPO, growth hormone (GH) or IVIG within one month of
 enrollment.

 No abnormalities of laboratory findings within one month of enrollment including the
 following: SGPT or SGOT greater than 5 times the normal value; Total bilirubin greater than
 3 times normal; BUN or creatinine greater than 2 times normal; Total WBC greater than
 150/mm(3) or ANC greater than 750/mm(3); Hemoglobin greater than 8.0 g/dl (transfusions are
 allowed); Platelet count greater than 100,000/mm(3).

 Not pregnant or not planning to become pregnant.

 No active substance abuse.

 Able to comply with the study requirements for scheduled evaluations such as periodic
 clinic visits or blood sampling.