Journal Article

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

Lama, Javier R., Lemos, Maria P., Segura, Patricia, Montano, Silvia M., De Rosa, Stephen C., Sanchez, Jorge, Lacherre, Martin, Buchbinder, Susan, Karuna, Shelly T., Ganoza, Carmela, Swann, Edith M., McElrath, M. Juliana, Grant, Shannon P.

2016

Overview

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. 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. 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. 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. ClinicalTrials.gov NCT02630082.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Activation / Adult / AIDS / AIDS vaccines / Biology and Life Sciences / Biopsy / CCR5 protein / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / Chlamydia / Circumcision / Circumcision, Male / Clinical trials / Cohort analysis / Cohort Studies / Complications / Gonorrhea / Health aspects / Health risk assessment / Health risks / HIV / HIV infections / HIV Infections - epidemiology / HIV Infections - immunology / HIV Infections - prevention & control / Homosexuality, Male / Human immunodeficiency virus / Humans / Immunity, Cellular / Infections / Lentivirus / Lymphocytes / Lymphocytes T / Male / Medical research / Medicine and Health Sciences / Mucosa / People and Places / Peripheral blood / Peru - epidemiology / Prevention / Rectum / Retroviridae / Risk / Risk Factors / Risk reduction / Safety / Sexual Behavior / Sexually transmitted diseases / Sigmoidoscopy / STD / Vaccines / Young Adult