title: Transient Peripheral Immune Activation follows Elective Sigmoidoscopy or Circumcision in a Cohort Study of MSM at Risk of HIV Infection.
abstract: BACKGROUND
  Rectal and genital sampling in HIV prevention trials permits assessments at the site of HIV entry. Yet the safety and acceptability of circumcision and sigmoidoscopy (and associated abstinence recommendations) are unknown in uncircumcised men who have sex with men (MSM) at high risk of HIV infection.
  
  
  METHODS
  Twenty-nine HIV-seronegative high-risk Peruvian MSM agreed to elective sigmoidoscopy biopsy collections (weeks 2 and 27) and circumcision (week 4) in a 28-week cohort study designed to mimic an HIV vaccine study mucosal collection protocol. We monitored adherence to abstinence recommendations, procedure-related complications, HIV infections, peripheral immune activation, and retention.
  
  
  RESULTS
  Twenty-three (79.3%) underwent a first sigmoidoscopy, 21 (72.4%) were circumcised, and 16 (55.2%) completed a second sigmoidoscopy during the study period. All who underwent procedures completed the associated follow-up safety visits. Those completing the procedures reported they were well tolerated, and complication rates were similar to those reported in the literature. Immune activation was detected during the healing period (1 week post-sigmoidoscopy, 6 weeks post-circumcision), including increases in CCR5+CD4+T cells and α4β7+CD4+T cells. Most participants adhered to post-circumcision abstinence recommendations whereas reduced adherence occurred post-sigmoidoscopy.
  
  
  CONCLUSIONS
  Rectosigmoid mucosal and genital tissue collections were safe in high-risk MSM. Although the clinical implications of the post-procedure increase in peripheral immune activation markers are unknown, they reinforce the need to provide ongoing risk reduction counseling and support for post-procedure abstinence recommendations. Future HIV vaccine studies should also consider the effects of mucosal and tissue collections on peripheral blood endpoints in trial design and analysis.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02630082.
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Lama
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Shelly T
authors.initials: ST
authors.lastname: Karuna
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Shannon P
authors.initials: SP
authors.lastname: Grant
authors.affiliation: Vaccine Clinical Research Branch, Division of AIDS, National Institutes of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Swann
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
authors.forename: Carmela
authors.initials: C
authors.lastname: Ganoza
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
authors.forename: Patricia
authors.initials: P
authors.lastname: Segura
authors.affiliation: US Naval Medical Research Unit No. 6, Callao, Peru.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Montano
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
authors.forename: Martin
authors.initials: M
authors.lastname: Lacherre
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Department of Global Health, University of Washington, Seattle, Washington, United States of America.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.affiliation: San Francisco Department of Health, San Francisco, California, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.affiliation: Asociacion Civil Impacta Salud y Educacion, Lima, Peru.|Department of Global Health, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.|Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Lemos
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002944:Circumcision, Male; D015331:Cohort Studies; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D018451:Homosexuality, Male; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D010568:Peru / Q000453:epidemiology; D012307:Risk Factors; D012725:Sexual Behavior; D012812:Sigmoidoscopy; D055815:Young Adult