title: Markers of HIV reservoir size and immune activation after treatment in acute HIV infection with and without raltegravir and maraviroc intensification.
abstract: BACKGROUND
  It is unclear whether intensification of standard highly active antiretroviral therapy (HAART) with entry and integrase inhibitors during acute HIV infection (AHI) could yield greater benefits in reducing markers for HIV reservoir size and immune activation.
  
  
  METHODS
  Thai patients with Fiebig I-IV AHI were prospectively enrolled and offered treatment. They were randomised 1:1 to HAART (tenofovir/emtricitabine/efavirenz,n=31) or megaHAART, a standard regimen intensified by raltegravir/maraviroc (n=31), during the first 24 weeks of therapy. Participants were monitored at weeks 0, 2, 4, 8 and 12, then every 12 weeks. Frequencies of peripheral blood mononuclear cells (PBMCs) carrying HIV DNA (total, integrated and 2-LTR episomes), plasma C-reactive protein (CRP) concentrations, and frequencies of activated T cells were measured. Flexible sigmoidoscopy was performed in willing participants (n=25) at baseline, weeks 24 and 96, and proviral DNA and RNA were determined.
  
  
  RESULTS
  Baseline characteristics were similar in the HAART and megaHAART arms. Median age was 28 years and 95% were men. Median CD4 cell count was 388 cells/mm3. HIV RNA was 5.6 log10copies/mL. HIV RNA declined more rapidly in the first 4 weeks with megaHAART (median -3.3 log10) than HAART (-2.6 log10). Time to achieve HIV RNA <50 copies/mL was shorter with megaHAART (median 55 days) than HAART (83 days,P=0.04). Viral suppression rates after week 12 did not differ between arms, and overall, 97% achieved suppression by week 48. The frequency of cells harbouring total HIV DNA was similarly low after 96 weeks in both treatment arms (median of 7 and 4 copies/106PBMCs in the megaHAART and HAART arms, respectively,P=0.41). At weeks 2 and 12, frequency of cells carrying 2-LTR circles were significantly higher with megaHAART (P=0.03). In the sigmoid colon, total HIV DNA and HIV RNA declined after treatment, with no differences between arms. The frequencies of cells with 2-LTR circles were also higher in the sigmoid colon at week 24 with megaHAART. Plasma levels of CRP and frequencies of CD4+ and CD8+ T cells expressing CD38 and HLA-DR or Ki67 were similar between arms.
  
  
  CONCLUSIONS
  Intensification of standard HAART with raltegravir and maraviroc was not associated with either statistically significant reductions of markers of HIV reservoir size in blood and sigmoid colon or markers of immune activation in blood.
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; US Military HIV Research Program, Bethesda, MD, USA.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: Vaccine and Gene Therapy Institute-Florida, Port St Lucie, FL, USA; Department of Microbiology, Infectiology and Immunology, Université de Montréal, Faculty of Medicine, and Centre de Recherche du CHUM, Montréal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: James Lk
authors.initials: JL
authors.lastname: Fletcher
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; US Military HIV Research Program, Bethesda, MD, USA.
authors.forename: Suteeraporn
authors.initials: S
authors.lastname: Pinyakorn
authors.affiliation: Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; Armed Forces Research Institute of Medical Sciences, US Component, Bangkok, Thailand.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Rungsun
authors.initials: R
authors.lastname: Rerknimitr
authors.affiliation: Leidos Biomedical Research Inc, Virus Isolation and Serology Laboratory, Frederick, MD, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Dewar
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kroon
authors.affiliation: Vaccine and Gene Therapy Institute-Florida, Port St Lucie, FL, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Vandergeeten
authors.affiliation: Armed Forces Research Institute of Medical Sciences, US Component, Bangkok, Thailand.
authors.forename: Rapee
authors.initials: R
authors.lastname: Trichavaroj
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nitiya
authors.initials: N
authors.lastname: Chomchey
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Thep
authors.initials: T
authors.lastname: Chalermchai
authors.affiliation: US Military HIV Research Program, Bethesda, MD, USA; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: US Military HIV Research Program, Bethesda, MD, USA; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
keywords: ART; Acute HIV infection; HIV DNA; immune activation; maraviroc; raltegravir; reservoir
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