Natascha Ching is a Pediatric Infectious Diseases specialist and Clinical Instructor, proposed Assistant Professor in Pediatrics, at the University of California, Los Angeles. The candidate's career objective is to become an independent investigator in patient oriented research, specializing in pediatric HIV-1 infection. The candidate became interested in the immune reconstitution of Pediatric HIV patients on highly active antiretroviral therapy (HAART) during fellowship. She initiated a prospective evaluation of cellular and humoral immune responses to recall antigens (tetanus booster/Hepatitis A). Based on her preliminary data, she expanded the project by learning a new technique of HIV cytotoxic T lymphocyte (CTL) peptide mapping to evaluate a cross-section of patients in the proposed study population. She detected HIV specific CTL responses in 82% of children and adolescents on HAART (undetectable viral load + HIV viremia). Autologous neutralizing antibody (ANAB) responses were also detected in pediatric HIV patients with prolonged viral suppression on HAART. This proposed career development plan will consist of closely mentored patient oriented research with Yvonne Bryson and Otto Yang as mentors, a structured laboratory evaluation of the clinical population along with a didactic curriculum in UCLA K30 translational research program.
Aims : We propose a prospective analysis of the protective immune correlates and viral containment in two well-characterized cohorts of pediatric HIV patients treated with HAART. We hypothesize that differences in the progression of pediatric HIV disease are directly related to variability in host immune pressures including HIV specific cellular immune responses (CDS CTL and CD4 help), ANAB responses and viral diversity and will be altered by initiation of HAART. Subjects: Cohort I is a group of chronically HIV-1 infected children/adolescents on HAART. Cohort II is a group of newly diagnosed perinatally HIV-1 infected infants prospectively randomized to early or deferred HAART, followed over 5 years. HIV specific cellular and humoral immune responses may vary according to the level and durability of virological responses to HAART in cohort I. Early treatment with HAART may contain viral replication, effect viral diversity, and preserve the immune system in cohort II. HIV cellular and humoral immune responses may vary between early vs. deferred treatment groups and by disease progression.
Ching, Natascha; Nielsen-Saines, Karin A; Deville, Jaime G et al. (2010) Autologous neutralizing antibody to human immunodeficiency virus-1 and replication-competent virus recovered from CD4+ T-cell reservoirs in pediatric HIV-1-infected patients on HAART. AIDS Res Hum Retroviruses 26:585-91 |