To evaluate the clinical, immunologic, and virologic effects of oral zidovudine (AZT) plus intravenous immunoglobulin (IVIG) versus AZT plus placebo (albumin). It is estimated that by 1991, there may be 10,000 to 20,000 HIV-infected children in the United States. HIV infection in children is most often associated with symptomatic disease and poor prognosis. Treatment with antiviral therapy may be effective in changing the course of disease and decreasing mortality in this vulnerable population. AZT treatment has been shown to decrease mortality and the frequency of opportunistic infections in certain adult AIDS patients; therefore, it is likely that children may also benefit from this antiviral therapy. In addition, bacterial infections are frequently found in HIV-infected children. Because pooled human serum immunoglobulin, another name for antibodies, is effective in reducing bacterial infection in patients with defects of immunity, it may reduce the rate of bacterial infection in HIV-infected children as well. In this study, AZT will be administered together with IVIG to determine safety, tolerance, and efficacy of the combined treatment.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Globulin, Immune  Drug: Zidovudine	Phase III

Further Study Details: 

Expected Total Enrollment:  250

It is estimated that by 1991, there may be 10,000 to 20,000 HIV-infected children in the United States. HIV infection in children is most often associated with symptomatic disease and poor prognosis. Treatment with antiviral therapy may be effective in changing the course of disease and decreasing mortality in this vulnerable population. AZT treatment has been shown to decrease mortality and the frequency of opportunistic infections in certain adult AIDS patients; therefore, it is likely that children may also benefit from this antiviral therapy. In addition, bacterial infections are frequently found in HIV-infected children. Because pooled human serum immunoglobulin, another name for antibodies, is effective in reducing bacterial infection in patients with defects of immunity, it may reduce the rate of bacterial infection in HIV-infected children as well. In this study, AZT will be administered together with IVIG to determine safety, tolerance, and efficacy of the combined treatment.

The study includes 250 children, 3 months to 12 years of age. All participants receive oral AZT. IVIG or intravenous placebo is administered every 28 days. Patients are followed for the development of serious bacterial infection, as well as for a number of factors relating to safety, tolerance, progression of disease, and survival. This is an outpatient study conducted over a minimum 100-week period. The children are evaluated every 2 weeks for the first 8 weeks, and monthly thereafter.

Ages Eligible for Study:  3 Months   -   12 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Allowed:

• Benadryl and/or acetaminophen may be given before and during intravenous immunoglobulin (IVIG) infusion in patients demonstrating mild reactions during infusion.
• Acetaminophen for short-term fever and pain.
• Zidovudine (AZT).
• Steroids.
• Oral or systemic (swish and swallow) nystatin.
• Maintenance therapy for fungal disease or tuberculosis.
• Prophylaxis for a previous episode of Pneumocystis carinii pneumonia (PCP) including the use of trimethoprim / sulfamethoxazole (TMP / SMX). The dosage is specified as TMP 75 mg/m2 twice daily 3 times a week and SMX 375 mg/m2 twice daily 3 times a week.
• Recommended:
• Children with AIDS and / or CD4 count = or < 500 cells/mm3 should receive primary PCP prophylaxis as described.

Concurrent Treatment: Allowed:

• Blood transfusion for hemoglobin < 8 g/dl and hematocrit < 24 percent or bone marrow suppression.
• Supplemental oxygen with a prestudy PaO2 < 70 mmHg.

Children must have one or more of the indicator diseases of AIDS; however, there must be an absence of acute opportunistic infection and an absence of bacterial infection requiring treatment at the time of entry into the study.

• Children with lymphoid interstitial proliferation (LIP) are excluded from enrollment unless they have had additional AIDS-defining opportunistic infections, meet ARC criteria, have had two or more serious bacterial infections in the 12 months prior to study entry, have evidence of HIV encephalopathy, or are currently on supplemental oxygen and steroids with a pre-treatment PaO2 < 70 mm Hg.
• Children with concurrent LIP and ARC are eligible for inclusion. Thrombocytopenia is an exclusion except if it is HIV-associated.
• Children randomized prior to their 13th birthday are eligible.
• All lab values must be within 4 weeks of study entry.

Prior Medication: Allowed:

• Zidovudine (AZT).

Exclusion Criteria

Co-existing Condition: Patients with the following will be excluded:

• Lymphoid interstitial proliferation (LIP) not requiring steroids and supplemental oxygen or with other lymphoproliferative diseases as their sole clinical evidence of HIV infection.
• Known hypersensitivity to immunoglobulin.
• Active HIV thrombocytopenia requiring IVIG therapy.

Concurrent Medication: Excluded:

• Chronic acetaminophen.
• Drugs that are metabolized by hepatic glucuronidation should not be used for more than 24 hours without notifying the study physician.
• Antibacterial prophylaxis for otitis, sinusitis, or urinary tract infection.
• Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP) prior to the first episode of laboratory-documented PCP.
• Immunoglobulin (IVIG) therapy required for active HIV thrombocytopenia.

Patients with the following will be excluded:

• Lymphoid interstitial proliferation (LIP) not requiring steroids and supplemental oxygen or with other lymphoproliferative diseases as their sole clinical evidence of HIV infection.
• Known hypersensitivity to immunoglobulin.
• Active HIV thrombocytopenia requiring IVIG therapy.
• Inability to establish or maintain intravenous access.
• Lack of parental or guardian authorization for intravenous access.

Prior Medication: Excluded within 4 weeks of study entry:

• Any other experimental therapy.
• Other antiretroviral agents.
• Drugs which cause prolonged neutropenia or significant nephrotoxicity.
• Immunoglobulins.
• Immunomodulating agents.

Active alcohol or drug abuse.

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      Kaiser Permanente / UCLA Med Ctr, Downey,  California,  902422814,  United States
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States
      Children's Hosp of Los Angeles/UCLA Med Ctr, Los Angeles,  California,  900276016,  United States
      Cedars Sinai / UCLA Med Ctr, Los Angeles,  California,  900481804,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
      Martin Luther King Jr Gen Hosp / UCLA Med Ctr, Los Angeles,  California,  900593019,  United States
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States
      Stanford Univ School of Medicine, Menlo Park,  California,  94025,  United States
      Northern California Pediatric AIDS Treatment Ctr / UCSF, San Francisco,  California,  94143,  United States
      Olive View Med Ctr, Sylmar,  California,  91342,  United States
Connecticut
      Univ of Connecticut Health Ctr / Pediatrics, Farmington,  Connecticut,  06032,  United States
Georgia
      Emory Univ School of Medicine, Atlanta,  Georgia,  30303,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Univ of Illinois College of Medicine, Chicago,  Illinois,  60612,  United States
Louisiana
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
      Univ of Massachusetts Med Ctr, Worcester,  Massachusetts,  01655,  United States
      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
New Jersey
      Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  071072198,  United States
New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Albert Einstein College of Medicine, Bronx,  New York,  10461,  United States
      Metropolitan Hosp Ctr, New York,  New York,  10029,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Columbia Univ Babies' Hosp, New York,  New York,  10032,  United States
      Lincoln Hosp Ctr / Pediatrics, Bronx,  New York,  10451,  United States
      SUNY / Health Sciences Ctr at Brooklyn / Pediatrics, Brooklyn,  New York,  11203,  United States
      Westchester Hosp / New York Med College / Pediatrics, Valhalla,  New York,  10595,  United States
      Schneider Children's Hosp / Long Island Jewish Med Ctr, New Hyde Park,  New York,  11042,  United States
      City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst,  New York,  11373,  United States
      Beth Israel Med Ctr / Pediatrics, New York,  New York,  10003,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      Columbus Children's Hosp, Columbus,  Ohio,  432052696,  United States
      Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati,  Ohio,  452670405,  United States
      Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
Pennsylvania
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Hermann Hosp / Univ Texas Health Science Ctr, Houston,  Texas,  77030,  United States
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States
Washington
      Children's Hosp of Seattle, Seattle,  Washington,  98105,  United States
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico
      UPR Children's Hosp / San Juan City Hosp, San Juan,  00936,  Puerto Rico
      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00619,  Puerto Rico

Study chairs or principal investigators

Spector, SA,  Study Chair

Study ID Numbers:  ACTG 051
Record last reviewed:  May 1994
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000720
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08