As part of the Institute of Human Virology, my research interests are primarily focused on antiretroviral clinical trials and novel therapeutic strategies for HIV treatment. This is particularly focused on strategies that will improve the rates of treatment success not only in the United States but also in resource limited settings. Examples of these studies include induction-maintenance strategies and the use of cell-cycle agents in combination with antiretrovirals. Dr. Redfield, Dr. Heredia and others from the IHV have demonstrated the ability of cell cycle agents such as hydroxyurea and rapamycin to downregulate CCR5 receptors and upregulate chemokine production. These strategies have the potential to increase the durability of treatment regimens while reducing costs and toxicities. We are developing studies to evaluate the activity of cell cycle agents in early infection and, in collaboration with Dr. Heredia and Dr. DeVico, we are evaluating the ability of cell cycle agents to reduce the number of CCR5 receptors in the cervical/vaginal tissue of macaques. If administration of cell cycle agents can reduce CCR5 receptors in cervical/vaginal tissue, future studies of their role in preventing transmission of HIV would be pursued.
In addition to therapy trials I also have an interest in therapeutic and preventive HIV vaccines. Recently, we completed a Phase I trial of a Tat toxoid vaccine, in HIV infected individuals produced by Aventis Pasteur, both alone and adjuvanted with Alum. A similar trial was completed in Belgium utilizing an experimental adjuvant, DC-Chol. Preliminary results in both trials demonstrated safety. I am also collaborating with George Lewis, Tony DeVico and others in the Vaccine Research Division in transitioning both the gp120-CD4 mimetic complex and the full length single chain gp120-CD4 complex into clinical trials, both as preventive and therapeutic agents. The gp120-CD4 vaccines are protein vaccines which have the potential to induce broadly neutralizing antibodies to primary isolates. Once the lot has been produced and vialed, a concept proposal will be presented for a safety and immunogencity trials in both healthy and HIV infected individuals. This is the first step in the development plan of the gp120-CD4 complex products.