A Multicenter Placebo-Controlled Trial To Evaluate the Safety and Efficacy of Oral Zidovudine in the Treatment of Children Infected With Human Immunodeficiency Virus With Mild to Moderate Symptoms (Including LIP)

Inclusion Criteria

Concurrent Medication:

Allowed:

• Prophylaxis for Pneumocystis carinii pneumonia (PCP) in children with AIDS or CD4 cell count = or < 500 cells/mm3.

Children must demonstrate the following clinical and laboratory findings:

• Laboratory evidence of HIV infection as demonstrated by either a positive viral culture or detectable serum p24 antigen or = or > two positive tests for HIV antibody, which must be determined by a federally licensed ELISA test and confirmed by Western blot.
• Children < 15 months of age, who are thought to have acquired HIV through perinatal transmission and whose only laboratory evidence of HIV infection is a positive antibody test, must also have one or more of the following laboratory criteria indicative of immunologic abnormality:
• hypergammaglobulinemia (IgG or IgA) defined as greater than the upper limit of normal for age-adjusted normals; absolute depression in the CD4+ cells to = or < 500 cells/mm3; decreased helper/suppressor ratio < 1.0; depressed in vitro mitogen response to at least one antigen/mitogen.
• Absence of serious bacterial infections as defined in Exclusion Criteria requiring therapy at the time of entry.
• Hemophiliacs are included.

Exclusion Criteria

Co-existing Condition:

Children will be excluded for the following reasons:

• Recurrent or life-threatening toxicity. Several allergic reactions such as exfoliative erythroderma, anaphylaxis, or vascular collapse. The presence of one or more of the indicator diseases of AIDS, such as opportunistic infections, malignancy, recurrent bacterial infections, or encephalopathy. Development of two or more episodes of recurrent varicella zoster infection or chronic zoster defined as = or > 30 days duration. Development of AIDS related complex, with failure to thrive, persistent or recurrent oral candidiasis, plus at least one of the following:
• Diarrhea that is either persistent or recurrent, lymphadenopathy at two or more noncontiguous sites, organomegaly, nephropathy manifested by nephrotic syndrome without evidence of renal failure, two or more episodes of herpes stomatitis or one or more episodes of herpes zoster within a 1 year period; plus at least one of the following:
• hypergammaglobulinemia, depression in the CD4+ cells to = or < 500/mm3, decreased helper/suppressor ratio < 1.0, depressed in vitro mitogen response to at least one antigen/mitogen.

Concurrent Medication:

Excluded:

• Hepatotoxic drugs.
• Steroids for lymphocytic interstitial pneumonitis (LIP).
• Prophylaxis for oral candidiasis, or otitis media.
• Immunoglobulin therapy.
• Chronic use of drugs that are metabolized by hepatic glucuronidation.

Concurrent Treatment:

Excluded:

• Supplemental oxygen treatment for lymphocytic interstitial pneumonitis (LIP).

Children will be excluded from the study for the following reasons:

• AIDS-defining opportunistic infection or neoplasm.
• Unexplained recurrent, serious bacterial infections (= or > 2 within a 2-year period) including sepsis, meningitis, pneumonia, abscess of an internal organ, and bone/joint infections caused by Haemophilus, Streptococcus, or other pyogenic bacteria.
• Encephalopathy.
• One or both of the following:
• Failure to thrive, defined as a child who crosses two percentile lines on the growth chart or a child who is less than the fifth percentile and does not follow the curve; and/or persistent (= or > 2 months) oral candidiasis despite appropriate topical therapy.
• Children with lymphocytic interstitial pneumonitis (LIP) who are steroid dependent or requiring supplemental oxygen or who have a pretreatment PaO2 < 70 mmHg.
• Children who qualify for the entrance criteria to open-label zidovudine (AZT) or AZT plus or minus gammaglobulin.

Prior Medication:

Excluded:

• Rifampin or rifampin derivatives.
• Antiretroviral agents.
• Zidovudine (AZT).
• Excluded within 2 weeks of study entry:
• Other experimental therapy.
• Drugs which cause prolonged neutropenia or significant nephrotoxicity.
• Excluded within 4 weeks of study entry:
• Immunomodulating agents including immunoglobulin, interferon, isoprinosine, and IL-2.

Prior Treatment:

Excluded within 4 weeks of study entry:

• Lymphocyte transfusions.

Active alcohol or drug abuse.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety