Transient Peripheral Immune Activation follows Elective Sigmoidoscopy or Circumcision in a Cohort Study of MSM at Risk of HIV Infection

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02630082" target="_blank">NCT02630082</a></p></div

MedDRA-coded Procedure Related Events.

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Immune Activation Associated with Interventional Procedures.

<p>A) Representative flow cytometry panels indicating live, CD3⁺, CD14^-, CD4⁺ cells and the gating scheme for CCR5⁺, Ki-67⁺Bcl-2^low, α4β7⁺, CD103⁺β7⁺, and CLA⁺ cells. 3 samples of 168 were excluded due to cell viability less than 70%.B) Percent CCR5⁺CD4⁺ T cells in blood over time. C) Percent α4β7⁺CD4+ T cells in blood over time. D) LBP concentration in serum over time. In panels B-D, dots indicate individual measurements, with box plots summarizing median and IQR; whiskers represent the range. S marks sigmoidoscopy visit, C indicates the circumcision visit. P-values are from Wilcoxon tests used to examine difference between sigmoidoscopy visits (week 2 and 27) and follow-up at weeks 3 and 28, respectively; only significant values are shown. Similar analysis was conducted comparing the circumcision visit (week 4) with the follow-up period including weeks 5 and 10.</p

Self-reported Demographic and Sexual Behavior of Study Participants During the Six Months Prior to Screening.^*

<p>Self-reported Demographic and Sexual Behavior of Study Participants During the Six Months Prior to Screening.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160487#t001fn001" target="_blank">*</a>}</p

Study Conduct.

<p>Flow chart indicates the number and percentage (%) of participants at screening who underwent procedures at each study visit. Also included are those who left the study, and the reasons why. The dashed boxes indicate the visit added after 8 participants had already completed the protocol.</p