title: Nelfinavir monotherapy increases naïve T-cell numbers in HIV-negative healthy young adults.
abstract: Although patients treated with HIV protease inhibitor (PI) containing regimens manifest increases in naïve T cell number, it is unclear whether this is due to reduction in viral replication or a direct drug effect. We questioned whether Nelfinavir monotherapy directly impacted naïve T-cell number in HIV-negative individuals. HIV-negative volunteers received Nelfinavir, 1250 mg orally, BID for 3 weeks, and T-cell receptor recombination excision circles (TREC) content in peripheral blood were assessed. Whereas TREC copies did not change over 3 weeks in untreated controls, TREC copies/copies CCR5 increased following Nelfinavir monotherapy in 8 patients (p < 0.02), and did not change in 7 patients (p = NS). Those patients who responded were younger than those who did not with a median age of 55 years for responders and 71 years for non-responders (p < 0.03). The increase in TREC was most pronounced in those patients less than 40-years old (p < 0.01). Moreover, the patients who did not increase TREC levels were more likely to have suffered a medical illness previously shown to reduce thymic function. In HIV-negative patients, monotherapy with the HIV PI Nelfinavir for 21 days increases TREC-positive naïve T cell number, particularly in individuals who are healthy and young.
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Stacey R
authors.initials: SR
authors.lastname: Rizza
authors.forename: Eric G
authors.initials: EG
authors.lastname: Tangalos
authors.forename: Mark D
authors.initials: MD
authors.lastname: McClees
authors.forename: Michael A
authors.initials: MA
authors.lastname: Strausbauch
authors.forename: Paul V
authors.initials: PV
authors.lastname: Targonski
authors.forename: David J
authors.initials: DJ
authors.lastname: McKean
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wettstein
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Badley
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D018023:HIV Seronegativity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D019888:Nelfinavir / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D017320:HIV Protease Inhibitors; D019888:Nelfinavir