Robert Redfield

Immune cell function testing: An adjunct to therapeutic drug monitoring in transplant patient management

Abstract:u2002 Each year, 55u2003000 organ transplants are performed worldwide. Cumulatively, the number of living organ recipients is now estimated to be over 300u2003000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Controlled doses of these drugs are required to prevent over‐medication, which may leave the patient susceptible to opportunistic infection and drug toxicity effects, or under‐dosing, which may lead to shortened graft survival because of rejection episodes.

Modification and structure–activity relationship of a small molecule HIV-1 inhibitor targeting the viral envelope glycoprotein gp120

This paper describes selected modification and structure-activity relationship of the small molecule HIV-1 inhibitor, 4-benzoyl-1-[(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2-(R)-methylpiperazine (BMS-378806). The results revealed: i) that both the presence and configuration (R vs. S) of the 3-methyl group on the piperazine moiety are important for the antiviral activity, with the 3-(R)-methyl derivatives showing the highest activity; ii) that the electronegativity of the C-4 substituent on the indole or azaindole ring seems to be important for the activity, with a small, electron-donating group such as a fluoro or a methoxy group showing enhanced activity, while a nitro group diminishes the activity; iii) that the N-1 position of the indole ring is not eligible for modification without losing activity; and iv) that bulky groups around the C-4 position of the indole or azaindole ring diminish the activity, probably due to steric hindrance in the binding. We found that a synthetic bivalent compound with two BMS-378806 moieties being tethered by a spacer demonstrated about 5-fold enhanced activity in an nM range against HIV-1 infection than the corresponding monomeric inhibitor. But the polyacrylamide-based polyvalent compounds did not show inhibitory activity at up to 200 nM.

Association between Longer Duration of HIV-Suppressive Therapy and Partial Recovery of the Vγ2 T Cell Receptor Repertoire

Human immunodeficiency virus (HIV) infection alters the function and repertoire of peripheral blood gamma delta T cells expressing the V gamma 2/V delta 2 T cell receptor (TCR). A cross-sectional comparison of the V gamma 2 TCR repertoire was performed for 56 HIV-infected subjects, 51 of whom were receiving highly active antiretroviral therapy (HAART), to measure changes in the V gamma 2 TCR repertoire. Longer durations of HAART were associated with partial recovery of the normal TCR repertoire, and recovery was greatest in subjects with complete virus suppression. Changes in the V gamma 2 TCR repertoire are sensitive measures for the effects of HAART and of residual HIV replication.