HIV & Infectious Diseases

Clinical research in pediatric and adolescent HIV infection

Washington, DC, is ranked first in the nation in HIV infection and AIDS prevalence, particularly among children and youth. This is the result of an overall high HIV prevalence rate in the community, previous high rates of perinatal transmission, and a growing number of behaviorally acquired cases of infection. Several investigators are involved in funded research looking at infection trends and responses to treatment. Dr. D’Angelo is the Principal Investigator for the Adolescent Trials Unit site in Washington, DC, part of the national Adolescent Trials Network. This 18-site network looks at a range of behavioral and biologic factors influencing HIV disease in adolescents and young adults. Currently nine protocols are open to patient enrollment focusing on early treatment interventions, adjunctive vitamin D therapy, vaginal microbicides, risk factors for HIV infection, pre-exposure prophylaxis and adherence to therapy. Dr. Rakhmanina collaborates with investigators at the MedStar Washington Hospital Center to look at the current algorithm used for maternal HIV testing during pregnancy and the use of antiretrovirals as prophylaxis of effective perinatal HIV transmission. Specifically, Dr. Rakhmanina is interested in determining whether any differences exist in transmission rates between African American women of U.S. origin and African immigrant mothers. In addition, she leads a multidisciplinary team of clinical researchers studying the most efficient mechanism of screening youth in pediatric Emergency Departments. Dr. Zeichner is the Principal Investigator for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group, a large multi-center international network of investigators sponsored by the NIH. IMPAACT sponsors many trials for HIVinfected children, including approaches to preventing infants born to HIV-infected mothers from acquiring the disease, and new drugs for HIV infection and the diseases that accompany HIV infection. The Children’s National IMPAACT site has sub-sites at MedStar Washington Hospital Center, where HIV-infected pregnant women are treated, and at Johns Hopkins University. Dr. Zeichner also is the Principal Investigator for an NIH-sponsored project to understand how HIV microbicides may affect the vaginal microbial flora as a way of understanding why some of the clinical trials of HIV microbicides failed. Dr. Zeichner is the local Principal Investigator for industry-sponsored studies that give HIVinfected children in the Washington area access to new investigational agents that may prove useful in patients for whom conventional therapies are no longer effective.

Faculty with interests in clinical research in pediatric and adolescent HIV infection include:

Pharmacology of antiretroviral therapies in children and adolescents

The treatment of HIV infection requires lifelong administration of multiple antiretroviral (ARV) agents. Dr. Rakhmanina focuses her research on the pharmacology of ARV therapy in pediatric patients. She specifically investigated the effects of developmental changes on the pharmacokinetics and pharmacodynamics of ARV therapy in children and adolescents. Her work in this field has contributed to the identification of saliva as a non-invasive alternative for therapeutic drug monitoring of nevirapine in children. She found that the recommended and approved dose of the ARV drug lopinavir provides suboptimal plasma concentrations in treatment-experienced children and adolescents and is related to suboptimal virus suppression. In collaboration with researchers from the University of California, Dr. Rakhmanina also has demonstrated subtherapeutic levels from crushed tablets of lopinavir when compared to the whole tablets in pediatric and adolescent patients with HIV infection. Dr. Rakhmanina works in close collaboration with Dr. Hoffman in the Center for Genetic Medicine Research to establish the effect of human host factors, such as mutations in CYP 450, MDR1, and SLCO genes on the metabolism and distribution of ARV drugs. Her most recent studies focus on the effect of puberty on the expression of the CYP2B6 enzyme and metabolism of the ARV drug efavirenz. These studies are aimed at creating effective paradigms for the study of HIV therapeutics that will lead to individualized therapy and improved outcome in pediatric and adolescent patients with HIV infection worldwide. Dr. Rakhmanina also is the Principal Investigator of several industry sponsored clinical trials of antiretroviral drugs in pediatric HIV patients receiving care at Children’s National.

Faculty with interests in the pharmacology of antiretroviral therapies in children and adolescents include: