Cyclosporin A provides no sustained immunologic benefit to persons with chronic HIV-1 infection starting suppressive antiretroviral therapy: results of a randomized, controlled trial of the AIDS Clinical Trials Group A5138.
BACKGROUND
Although the determinants of immune deficiency and immune restoration in chronic human immunodeficiency virus (HIV)-1 infection are not well understood, immune activation has been proposed as being central to the pathogenesis of HIV.


METHODS
A randomized, controlled trial of cyclosporin A treatment for 2 weeks was performed in persons with chronic HIV-1 infection who were beginning a standardized antiretroviral therapy (ART) regimen.


RESULTS
Treatment with cyclosporin A provided only a marginal and transient enhancement in circulating T cell restoration that was largely restricted to cells expressing the CCR7 chemokine receptor and that did not persist beyond 2 weeks.


CONCLUSIONS
Cyclosporin A coadministered for 2 weeks with ART provided no sustained immunologic benefit to persons with chronic HIV-1 infection. If immune activation drives progressive immune deficiency in chronic HIV-1 infection, these activation pathways may not be sensitive to cyclosporin.
Lederman
Michael M
MM
Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH 44106, USA. MXL6@case.edu
Smeaton
Laura
L
Smith
Kim Y
KY
Rodriguez
Benigno
B
Pu
Minya
M
Wang
Hongying
H
Sevin
Anne
A
Tebas
Pablo
P
Sieg
Scott F
SF
Medvik
Kathy
K
Margolis
David M
DM
Pollard
Richard
R
Ertl
Hildegund C J
HC
Valdez
Hernan
H
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D007166:Immunosuppressive Agents; D019707:Receptors, Chemokine; D016572:Cyclosporine