title: Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV.
abstract: OBJECTIVE
  To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+).
  
  
  METHODS
  24-week randomized open-label prospective evaluation.
  
  
  METHODS
  Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls.
  
  
  RESULTS
  At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group.
  
  
  CONCLUSIONS
  A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART.
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Valcour
authors.affiliation: Department of Neurology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Serena S
authors.initials: SS
authors.lastname: Spudich
authors.affiliation: Huntington Medical Research Institutes, Pasadena, California, United States of America.
authors.forename: Napapon
authors.initials: N
authors.lastname: Sailasuta
authors.affiliation: South East Asia Research Collaboration with Hawaii, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Sukalaya
authors.initials: S
authors.lastname: Lerdlum
authors.affiliation: South East Asia Research Collaboration with Hawaii, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: James L K
authors.initials: JL
authors.lastname: Fletcher
authors.affiliation: South East Asia Research Collaboration with Hawaii, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.|Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, United States Component, Bangkok, Thailand.
authors.forename: Eugene D M B
authors.initials: ED
authors.lastname: Kroon
authors.affiliation: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Jagodzinski
authors.affiliation: Department of Biostatistics and Epidemiology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Isabel E
authors.initials: IE
authors.lastname: Allen
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Collin L
authors.initials: CL
authors.lastname: Adams
authors.affiliation: South East Asia Research Collaboration with Hawaii, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Peeriya
authors.initials: P
authors.lastname: Prueksakaew
authors.affiliation: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
authors.forename: Bonnie M
authors.initials: BM
authors.lastname: Slike
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Hellmuth
authors.affiliation: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.|United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C584933:CCR5 protein, human; D019428:HIV Integrase Inhibitors; D019713:Receptors, CCR5