Raltegravir Activity In Lymphoid Tissues

Withdrawn before enrolling · Not applicable

Conditions studied: HIV Infection, HIV Infections

In brief

The reduction with antiretroviral therapy (ART) of HIV RNA in blood, and HIV RNA in infected cells and in viruses associated with the follicular dendritic cell (FDC) network in lymphatic tissues, typically follows a two-phase pattern of decline. The half-life of the first-phase is about 1 day and that of the second phase is about 14 days, with comparable estimates for first-phase decay in SIV-infected rhesus macaques. While substantial evidence supports the current view that first-phase decay reflects the death of activated CD4+ T cells infected before ART was begun, the sources of viral RNA in the second phase have not as yet been conclusively established. Possible sources of viral RNA that have been invoked in mathematical models, or for which there is experimental evidence, include longer-lived infected cells such as macrophages and resting CD4+ T cells, dissociation of virus from the FDC network, and productively infected CD4+ T cells that are not subject to clearance by host immune responses because of waning levels of HIV antigen. Raltegravir (MK-0518) belongs to a new class of integrase inhibitors that potently suppress HIV and SIV replication, and reportedly markedly alters the second phase HIV decline in a way that challenges the current view that longer-lived infected cells are the source of virus in this phase. While mathematical modeling of decay of HIV RNA in blood was most consistent with 1) cells newly infected by long-lived cells, or 2) from activation of latently infected cells with full-length unintegrated HIV DNA as a source of second phase virus, we think the data are also quite consistent with the greater efficacy of integrase inhibitors in a particular cell type and/or anatomic site such as the gut. In this protocol we will test the hypothesis that the rapid decrease in HIV replication associated with raltegravir is due to a more complete suppression of viral replication in lymphatic compartments such as lymph nodes and gastrointestinal lymphatic tissue. We will also investigate compartment-specific intracellular levels of raltegravir to potentially explain differences in changes in these compartments.

Key facts

Study ID

NCT00863668

Run by

University of Minnesota

People needed

0

Starts

2009-03-01

Expected to finish

2011-03-01

Last updated by the study team

2015-05-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• HIV positive (proven serologically at the time of screen, unless evidence for seroconversion)
• Evidence of recent (proven seroconversion within 4 months) or acute infection (HIV antibody negative, HIV RNA positive), or CD4 T Cells > 350 in peripheral blood and plasma viral load > 100,000 copies/ml
• Antiretroviral therapy naive (no prior history of antiretroviral therapy)
• Negative pregnancy test for eligible women of childbearing potential

You may not qualify if…

• Contraindication to surgical and endoscopic procedures (as judged by the principal investigator)
• Psychiatric or psychological illness that would make adherence to protocol procedures unlikely
• Pregnancy

Where it is running

• University of Minnesota Medical Center, Division of Infectious Diseases — Minneapolis, Minnesota, United States

Full record on ClinicalTrials.gov

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