title: Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection.
abstract: BACKGROUND
  Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.
  
  
  RESULTS
  We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm(3). HIV RNA was 5.5 log(10) copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/10(6) PBMC) vs. Fiebig I (8 copy/10(6) PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).
  
  
  CONCLUSIONS
  Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.
authors.affiliation: South East Asia Research Collaboration with Hawaii, Pathumwan, Bangkok, Thailand. jintanat.a@searchthailand.org
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.forename: Claire
authors.initials: C
authors.lastname: Vandergeeten
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Mark
authors.initials: M
authors.lastname: de Souza
authors.forename: Rungsun
authors.initials: R
authors.lastname: Rerknimitr
authors.forename: Robin
authors.initials: R
authors.lastname: Dewar
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.forename: Frits
authors.initials: F
authors.lastname: van Griensven
authors.forename: Rafick
authors.initials: R
authors.lastname: Sekaly
authors.forename: Suteeraporn
authors.initials: S
authors.lastname: Pinyakorn
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.forename: Rapee
authors.initials: R
authors.lastname: Trichavaroj
authors.forename: Wiriya
authors.initials: W
authors.lastname: Rutvisuttinunt
authors.forename: Nitiya
authors.initials: N
authors.lastname: Chomchey
authors.forename: Robert
authors.initials: R
authors.lastname: Paris
authors.forename: Sheila
authors.initials: S
authors.lastname: Peel
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.forename: Frank
authors.initials: F
authors.lastname: Maldarelli
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Nelson
authors.initials: N
authors.lastname: Michael
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007422:Intestines / Q000276:immunology* / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D019713:Receptors, CCR5 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D019562:Viral Load; D017735:Virus Latency / Q000276:immunology*
chemical_list: D016207:Cytokines; D019713:Receptors, CCR5