title: Cross-sectional detection of acute HIV infection: timing of transmission, inflammation and antiretroviral therapy.
abstract: BACKGROUND
  Acute HIV infection (AHI) is a critical phase of infection when irreparable damage to the immune system occurs and subjects are very infectious. We studied subjects with AHI prospectively to develop better treatment and public health interventions.
  
  
  METHODS
  Cross-sectional screening was employed to detect HIV RNA positive, antibody negative subjects. Date of HIV acquisition was estimated from clinical history and correlated with sequence diversity assessed by single genome amplification (SGA). Twenty-two cytokines/chemokines were measured from enrollment through week 24.
  
  
  RESULTS
  Thirty-seven AHI subjects were studied. In 7 participants with limited exposure windows, the median exposure to HIV occurred 14 days before symptom onset. Lack of viral sequence diversification confirmed the short duration of infection. Transmission dates estimated by SGA/sequencing using molecular clock models correlated with transmission dates estimated by symptom onset in individuals infected with single HIV variants (mean of 28 versus 33 days). Only 10 of 22 cytokines/chemokines were significantly elevated among AHI participants at enrollment compared to uninfected controls, and only 4 participants remained seronegative at enrollment.
  
  
  CONCLUSIONS
  The results emphasize the difficulty in recruiting subjects early in AHI. Viral sequence diversity proved accurate in estimating time of infection. Regardless of aggressive screening, peak viremia and inflammation occurred before enrollment and potential intervention. Given the personal and public health importance, improved AHI detection is urgently needed.
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America. cynthia_gay@med.unc.edu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gay
authors.forename: Oliver
authors.initials: O
authors.lastname: Dibben
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Anderson
authors.forename: Andrea
authors.initials: A
authors.lastname: Stacey
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Mayo
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: JoAnn D
authors.initials: JD
authors.lastname: Kuruc
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: Charles
authors.initials: C
authors.lastname: Hicks
authors.forename: David
authors.initials: D
authors.lastname: Margolis
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Barton
authors.initials: B
authors.lastname: Haynes
authors.forename: Ronald
authors.initials: R
authors.lastname: Swanstrom
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D001499:Bayes Theorem; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D003430:Cross-Sectional Studies; D003710:Demography; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000635:transmission*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D019562:Viral Load; D055815:Young Adult
chemical_list: D018925:Chemokines