title: Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4+ T-cell response: a randomized controlled trial.
abstract: BACKGROUND
  Despite virally suppressive combination antiretroviral therapy (cART), some HIV-infected patients exhibit suboptimal CD4(+) T-cell recovery. This study aimed to determine the effect of intensification of cART with raltegravir or addition of hyperimmune bovine colostrum (HIBC) on CD4(+) T-cell count in such patients.
  
  
  METHODS
  We randomized 75 patients to 4 treatment groups to receive raltegravir, HIBC, placebo, or both raltegravir and HIBC in a factorial, double-blind study. The primary endpoint was time-weighted mean change in CD4(+) T-cell count from baseline to week 24. T-cell activation (CD38(+) and HLA-DR(+)), plasma markers of microbial translocation (lipopolysaccharide, 16S rDNA), monocyte activation (soluble (s) CD14), and HIV-RNA (lowest level of detection 4 copies/mL) were monitored. Analysis was performed using linear regression methods.
  
  
  RESULTS
  Compared with placebo, the addition of neither raltegravir nor HIBC to cART for 24 weeks resulted in a significant change in CD4(+) T-cell count (mean difference, 95% confidence interval [CI]: 3.09 cells/μL, -14.27; 20.45, P = .724 and 9.43 cells/μL, -7.81; 26.68, P = .279, respectively, intention to treat). There was no significant interaction between HIBC and raltegravir (P = .275). No correlation was found between CD4(+) T-cell count and plasma lipopolysaccharide, 16S rDNA, sCD14, or HIV-RNA.
  
  
  CONCLUSIONS
  The determinants of poor CD4(+) T-cell recovery following cART require further investigation.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00772590, Australia New Zealand Clinical Trials Registry: ACTRN12609000575235.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. hbyakwaga@kirby.unsw.edu.au
authors.forename: Helen
authors.initials: H
authors.lastname: Byakwaga
authors.forename: Mark
authors.initials: M
authors.lastname: Kelly
authors.forename: Damian F J
authors.initials: DF
authors.lastname: Purcell
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Hila
authors.initials: H
authors.lastname: Haskelberg
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: Roger
authors.initials: R
authors.lastname: Garsia
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boyd
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
mesh_terms: D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D003126:Colostrum / Q000276:immunology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000276:immunology / Q000302:isolation & purification; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016014:Linear Models; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium