We propose to develop a pediatric AIDS clinical trials group at the Babies Hospital, Division of the Presbyterian Hospital in the City of New York, and Harlem Hospital Center in northern Manhattan, both of which are units of the Columbia University College of Physicians & Surgeons. We have commitment, capability, and relevant patient population to participate in drug studies of infants and children infected with human immunodeficiency virus (HIV). There is a serious need for such a project because we are at the epicenter of the acquired immunodeficiency syndrome (AIDS) epidemic in women and children. As a result, we have a large, localized population that is a major resource for testing potential methods of treatment. Moreover, this population now has no access to drug protocols against HIV. Our hospitals serve communities where IV drug abuse is widespread and where 2-4% of all newborn infants are seropositive against HIV (of which 40% are probably infected). We predict that in the next 5 years 50-120 HIV infected infants per year will be born in our hospitals. The expertise at Babies Hospital in designing, conducting, and analyzing clinical trials, together with the extensive experience at Harlem Hospital in dealing with the sociological complexities of providing health care to HIV-infected children and their families, provides an ideal collaborative structure for the development, evaluation, and implementation of therapeutic drug regimens. We propose to evaluate a hypothetical new anti-retroviral drug we have called """"""""ENDAIDS"""""""" (Phases I, II, & III). While no such drug yet exists, a protocol is presented to illustrate how a potentially useful compound when available, can be tested in our population of patients and with our facilities. We will study the pharmacokinetics, toxicity, and efficacy (measuring clinical, immunologic, and virological indicators) of ENDAIDS in infants and children proven to be infected with HIV. We will also develop improved methods for the diagnosis of HIV infection, especially in young infants, and we will develop strategies to help disadvantaged parents to care for their HIV infected children. Phase I will involve 10 symptomatic children and will be designed to detect drug toxicity and to evaluate the pharmacokinetics of ENDAIDS over 10 weeks. Baseline and follow up clinical, virological, and immunological tests will be performed. If there is no limiting toxicity, we will conduct Phase II studies in 30 ambulatory HIV infected subjects for continued evaluation of safety and beginning studies on efficacy of ENDAIDS. Because of the uniformly fatal outcome of untreated AIDS, considerable toxicity can be acceptable in a useful drug. Limiting toxicity would be that which itself is life-threatening or which irreversibly impairs the quality of life. Treatment will be for 1 year in Phase II with use of strategies to maximize chance of patient follow up and compliance. Subjects will be followed medically at intervals and evaluated with regard to their growth, development, resistance to opportunistic infections, drug compliance, and virologic and immunologic indicators of control of disease. Monitoring for toxicity of ENDAIDS will be performed. Improvement in symptoms and in laboratory indicators will be interpreted as a positive effect of ENDAIDS against HIV. If potential benefits of ENDAIDS appear to outweigh its risks, randomized, controlled phase III studies will begin. The efficacy of ENDAIDS will be compared with that of AZT symptomatic subjects. ENDAIDS will be also compared with AZT and placebo in addition asymptomatic subjects. The groups will be compared with regard to duration and quality of life, opportunistic infections, and changes in virologic and immunologic indicators of disease. In selected patients, respiratory, cardiac, and neurologic status will also be evaluated prospectively.
