title: Addition of cyclophosphamide to antiretroviral therapy does not diminish the cellular reservoir in HIV-infected persons.
abstract: The chronically HIV-infected cellular reservoir in lymphoid tissue (LT) represents a formidable obstacle to the long-term success of antiretroviral therapy. Cytoreductive chemotherapy with cyclophosphamide (CTX) reduces cells in LT, and we hypothesized that coadministration of antiretroviral therapy with CTX may diminish the cellular reservoir over time. Ten antiretroviral treatment-naive subjects were recruited, and they received stavudine, lamivudine and nelfinavir (antiretroviral therapy, ART) until 2 consecutive plasma HIV RNA levels measured < 50 copies/ml (step 1). Five subjects then received ART alone, whereas five subjects received ART plus three escalating doses of CTX (step 2). Viral DNA was measured in LT obtained by excisional lymph node biopsy and peripheral blood mononuclear cells (PBMCs), using quantitative polymerase chain reaction at three time points in both groups (before steps 1 and 2, and after CTX). Viral DNA declined in both groups after the initiation of ART alone in step 1. During step 2 both groups experienced a modest decline compared with step 1. However, no significant differences were observed in viral DNA in LT or PBMCs between the ART alone and the ART plus CTX groups. Suppression of plasma HIV RNA levels < 50 copies/ml was not maintained in the ART plus CTX group, perhaps because of inadequate medication adherence. The group receiving ART plus CTX had lower CD4(+) lymphocyte counts and absolute total lymphocytes compared with the ART alone group. We conclude that the addition of CTX to ART did not diminish the cellular reservoir in HIV-infected persons.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. jab5@acpub.duke.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Bartlett
authors.forename: G Diego
authors.initials: GD
authors.lastname: Miralles
authors.forename: Anne D
authors.initials: AD
authors.lastname: Sevin
authors.forename: Martha
authors.initials: M
authors.lastname: Silberman
authors.forename: Scott K
authors.initials: SK
authors.lastname: Pruitt
authors.forename: Janet
authors.initials: J
authors.lastname: Ottinger
authors.forename: Victoria
authors.initials: V
authors.lastname: Gryszowska
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: R Pat
authors.initials: RP
authors.lastname: Bucy
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008221:Lymphoid Tissue / Q000821:virology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000821:virology; D019888:Nelfinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D003520:Cyclophosphamide; D018119:Stavudine; D019888:Nelfinavir