DESCRIPTION (provided by applicant): Candidate: Dr. Grace John-Stewart has had a highly productive research career focusing on international HIV-1 studies in Africa, particularly focused on mother-to-child transmission of HIV-1. She has mentored over 20 clinician-researchers, and 3 individuals who have received K-awards. For the K24 Mid-Career Investigator Award, the candidate, Dr. John-Stewart, proposes to develop a research program on pediatric HIV-1 treatment in Africa using historical and new research cohorts. The candidate has excellent research support that will provide many opportunities for new clinical-research trainees. Research: Pediatric HIV-1 treatment lags considerably behind adult treatment in newly expanded programs in Africa, in part because of insufficient experience and data. HIV-1 infected infants have staggeringly high mortality with >50% of untreated infants dying before 2 years of age. Infant immune development, HAART adherence, and the use of surrogate markers for therapeutic decision-making are key areas requiring further research to guide pediatric HIV-1 treatment programs. The aims proposed for the K24 are: 1. To determine effects of HIV-1 on the developing infant immune system by comparing immunologic parameters in infants who are HIV-1 uninfected, HIV-1 infected treated with early HAART, and HIV-1 infected untreated. 2. To determine adherence and rates of viral suppression among infants initiating HAART in the first few months of life. 3. To determine sensitivity, specificity, and predictive value of clinical markers, CD4%, and HIV-1 RNA for guiding therapeutic change during infancy in African HIV-1 infected infants. Relevance: The new studies will provide opportunities for trainees interested in pediatrics, immunology, HAART adherence, and HIV-1 treatment. Dr. John-Stewart's familiarity with conducting research in Africa and breadth of experience will contribute to excellent mentorship. The K24 will allow Dr. John-Stewart to develop new pediatric HIV-1 research and to mentor a new cadre of clinical researchers. Currently, about 90% of HIV-1 infected children worldwide reside in Africa. The proposed studies will be relevant to pediatric HIV-1 treatment programs and will contribute to improved health-care and child survival in Africa.