title: Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study.
abstract: BACKGROUND
  People infected with HIV have a higher risk for developing insulin resistance, diabetes, and cardiovascular disease than the general population. Dipeptidyl peptidase IV (DPP4) inhibitors are glucose-lowering medications with pleiotropic actions that may particularly benefit people with HIV, but the immune and virological safety of DPP4 inhibition in HIV is unknown.
  
  
  OBJECTIVE
  DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive adults.
  
  
  METHODS
  This was a randomized, placebo-controlled, double-blind safety trial of sitagliptin in HIV-positive adults.
  
  
  METHODS
  The study was conducted at an academic medical center.
  
  
  METHODS
  Twenty nondiabetic HIV-positive men and women (9.8 ± 5.5 years of known HIV) taking antiretroviral therapy and with stable immune (625 ± 134 CD4+ T cells per microliter) and virological (<48 copies HIV RNA per milliliter) status.
  
  
  METHODS
  The intervention included sitagliptin (100 mg/d) vs matching placebo for up to 24 weeks.
  
  
  METHODS
  CD4+ T cell number and plasma HIV RNA were measured every 4 weeks; fasting serum regulated upon activation normal T-cell expressed and secreted (RANTES), stromal derived factor (SDF)-1α, Soluble TNF receptor II, and oral glucose tolerance were measured at baseline, week 8, and the end of study. ANOVA was used for between-group comparisons; P < .05 was considered significant.
  
  
  RESULTS
  Compared with placebo, sitagliptin did not reduce CD4+ T cell count, plasma HIV RNA remained less than 48 copies/mL, RANTES and soluble TNF receptor II concentrations did not increase. SDF1α concentrations declined (P < .0002) in the sitagliptin group. The oral glucose tolerance levels improved in the sitagliptin group at week 8.
  
  
  CONCLUSIONS
  Despite lowering SDF1α levels, sitagliptin did not adversely affect immune or virological status, or increase immune activation, but did improve glycemia in healthy, nondiabetic HIV-positive adults. These safety data allow future efficacy studies of sitagliptin in HIV-positive people with cardiometabolic complications.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Goodwin
authors.forename: Dominic N
authors.initials: DN
authors.lastname: Reeds
authors.forename: Michael
authors.initials: M
authors.lastname: Royal
authors.forename: Heidi
authors.initials: H
authors.lastname: Struthers
authors.forename: Erin
authors.initials: E
authors.lastname: Laciny
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Yarasheski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011719:Pyrazines / Q000009:adverse effects* / Q000494:pharmacology; D012367:RNA, Viral / Q000276:immunology; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D012367:RNA, Viral; D014230:Triazoles; D000068900:Sitagliptin Phosphate