This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a study on the latently infected reservoir of replication-competent HIV in resting memory CD4 cells. The major objective is to determine whether a combination of T20 plus tenofovir + lamivudine + saquinavir + ritonavir can reduce the HIV in the latently infected reservoir. This persistence of HIV in the long-lived reservoir is considered to be one possible reason for the failure to eradicate the HIV with standard antiretroviral therapy. Activated T cells enter a memory state, and if activated CD4 cells with integrated HIV revert to the resting memory state, these cells could serve as a latent reservoir. Then subsequent activation of these cells could result in re-emergence of the HIV. T20 is a peptide motif found within the gp41 transmembrane protein of HIV and binds to gp41, a protein involved in the fusion of HIV to the host cell membrane. This HIV drug is therefore the first in a class of fusion inhibitors. One group (Dr. Siliciano) has identified HIV by a PCR assay in resting CD4 T cells, and these cells when activated produced HIV. In patients who were treated with antiretroviral therapy and responded, there was no change in the HIV level in the resting CD4 cell population. In this open-label, single-arm, pathophysiology study, the major objective is to determine whether a combination of T20 plus tenofovir + lamivudine + saquinavir + ritonavir can reduce HIV in the resting CD4 cells. The patient's peripheral blood CD4 cells will be purified by magnetic beads, activated by allogeneic feeder cells and uninfected CD8-depleted lymphoblasts. HIV replication will then be monitored using p24 production. Treatment will consist of 96 weeks of administration in HIV patients with >1000 copies of HIV RNA and CD4 >100 and previously untreated. Patients with drug-resistant strains, determined by genotyping, will be ineligible. Once the HIV is <50 copies, the latent cell reservoir HIV will be measured at weeks 48, 72 and 96. Those who do not achieve <50 copies of HIV can continue on T20. The study's significance is that T20 plus ART may be able to reduce HIV in the latent cell reservoir.
Showing the most recent 10 out of 470 publications
