title: Reduced inflammation and CD4 loss in acute SHIV infection during oral pre-exposure prophylaxis.
abstract: BACKGROUND
  The impact of pre-exposure prophylaxis (PrEP) with antiretrovirals on breakthrough HIV or SHIV infection is not fully documented. We addressed the hypothesis that SHIV(SF162P3) infection despite active PrEP results in altered early immune parameters, compared with untreated infection.
  
  
  METHODS
  Eleven rhesus macaques were infected during repeated, rectal, low-dose SHIV(SF162P3) exposures while receiving concurrent oral PrEP (Truvada [n = 2] or GS7340 [n = 4]) or as untreated controls (n = 5). We measured SHIV RNA, inflammatory cytokines, CD4 cells, and SHIV-specific and memory T cells until 20 weeks after peak viremia.
  
  
  RESULTS
  SHIV infection during PrEP resulted in 100-fold lower peak viremia and lower IL-15, IL-18, and IL-1Ra levels, compared with controls (P < .05; Wilcoxon rank-sum test). Unlike controls, PrEP-treated macaques showed no significant CD4 cell count reduction during acute infection and developed more SHIV-specific central memory T cells, relative to controls. After in vivo CD8 cell depletion, viral load increased to similar levels, indicating that CD8 cells were critical for viral control in both groups.
  
  
  CONCLUSIONS
  PrEP with antiretrovirals has beneficial effects on early SHIV infection even when infection is not prevented. Although long-term immune control could not be examined in this SHIV infection model, our results suggest that PrEP results in improved early disease parameters in breakthrough infections.
authors: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. egk6@cdc.gov
authors: Ellen N
authors: EN
authors: Kersh
authors: Wei
authors: W
authors: Luo
authors: Qi
authors: Q
authors: Zheng
authors: Debra R
authors: DR
authors: Adams
authors: Debra
authors: D
authors: Hanson
authors: Ae S
authors: AS
authors: Youngpairoj
authors: Mian-er
authors: ME
authors: Cong
authors: Katherine
authors: K
authors: Butler
authors: R Michael
authors: RM
authors: Hendry
authors: Janet M
authors: JM
authors: McNicholl
authors: Walid
authors: W
authors: Heneine
authors: J Gerardo
authors: JG
authors: Garcia-Lerma
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000409:Alanine; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004338:Drug Combinations; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D018709:Statistics, Nonparametric; D000068698:Tenofovir / Q000031:analogs & derivatives; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D016207:Cytokines; D004338:Drug Combinations; D000069480:Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D009943:Organophosphorus Compounds; D012367:RNA, Viral; D003841:Deoxycytidine; D000068698:Tenofovir; C442442:tenofovir alafenamide; D000225:Adenine; D000409:Alanine