Skip to main content
OpenTrials
Completed

NCT Number: NCT02630082

Feasibility of Measuring Immune Resp, Activation in Foreskin/Mucosa in HIV-, Uncircumcised High-HIV-risk MSM, Lima Peru

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. The purpose of this study is to evaluate the feasibility of methods for assessing baseline characteristics of the mucosa of MSM at risk of HIV infection in Lima, Peru.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

HIV Infections Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Disease Attributes Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections Pathologic Processes Pathological Conditions, Signs and Symptoms RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

21 year–30 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

About this study

The worldwide HIV/AIDS epidemic may only be controlled through development and utilization of a safe and effective vaccine that will prevent HIV infection. To fill gaps in the understanding of HIV vaccines, studies of mucosal immunity aim to complement assessments of systemic immunity. Yet it is unclear, and important to understand, how mucosal collections and the kinetics of immune activation they might initiate may impact peripheral blood endpoints in HIV vaccine trials. The HIV Vaccine Trials Network (HVTN) and the National Institute of Allergy and Infectious Diseases (NIAID) are conducting a single-site, exploratory cohort study evaluating the feasibility of sampling mucosa and assessing cellular immune responses in sexually active men who have sex with men, a population in which later-phase HIV vaccine clinical trials are often conducted.

The primary purpose of HVTN 914 is to assess the feasibility of performing safe and tolerable circumcision and rectosigmoid biopsy studies on a study population of 30 healthy, HIV-seronegative, uncircumcised men in Lima, Peru, aged 21 to 30 years, who have sex with men and who are at high risk for acquisition of HIV; to assess institutional capacities to process mucosal samples; and to identify methods of evaluating foreskin and rectosigmoid mucosal immune responses that provide minimal variability for analysis of small sample sizes.

The study is designed to mimic an HIV vaccine study mucosal collection protocol. Participants agree to elective sigmoidoscopy biopsy collections and circumcision, and actively participate in this study for approximately 7 months. The primary analysis will focus on pre- and post-procedure retention, safety laboratory values, sexual satisfaction, HIV risk behaviors, and levels of activation markers associated with vulnerability to HIV infection in samples of peripheral blood mononuclear cells. A total of 11 study visits (including a screening visit) occur at Weeks 0-5, 10, and 26-28. Study procedures include physical exams, blood and urine collection, HIV testing, and questionnaire. Elective rectosigmoid bioscopy is performed at Weeks 2 and 27. Elective circumcision is performed at Week 4. Some blood collected from participants will be stored and used in future research. Risk-reduction counseling will be conducted at all study visits.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male, age 21 to 30 years, who, in the 6 months prior to screening, experienced 1 or both of the following HIV risk criteria:
  • unprotected anal intercourse with 1 or more male or MTF transgender partner(s); or
  • anal intercourse with 2 or more male or MTF transgender partners. Note: Volunteers who have been in a monogamous relationship with an HIV-seronegative partner for > 6 months are excluded.
  • Ability and willingness to provide informed consent
  • Assessment of understanding: volunteer demonstrates understanding of the procedures and purpose of this study. Participants will complete a questionnaire prior to enrollment with verbal demonstration of understanding of all questionnaire items answered incorrectly.
  • Willingness to receive HIV test results
  • Willingness to discuss HIV infection risks (including sexual behavior and drug use) and amenable to HIV risk reduction counseling
  • Willingness to undergo phlebotomy, rectal swab, sigmoidoscopy, and circumcision
  • Willingness to adhere to safety protocols before and after sigmoidoscopy and circumcision
  • Agrees not to enroll in another study of an investigational research agent prior to completion of the last required protocol clinic visit
  • Hemoglobin ≥ 13.0 g/dL
  • White blood cell (WBC) count = 3300 to 12,000 cells/mm3
  • Total lymphocyte count ≥ 800 cells/mm3
  • Remaining differential either within institutional normal range or with site physician approval
  • Platelets = 125,000 to 550,000/mm3
  • Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.25 institutional upper limit of normal; International Normalized Ratio (INR) ≤ 1.5
  • Negative HIV-1 and -2 blood test: May use locally available assays that have been approved by HVTN Laboratory Operations.

Exclusion criteria

  • Volunteers who, in the six months prior to screening, have had sexual partners known to be HIV-infected
  • Volunteers who, for the 6 months prior to screening, have been in a monogamous relationship with an HIV-seronegative partner
  • History of immunodeficiency
  • Foreskin covering less than half the glans
  • Absolute medical indication for circumcision (balanitis or phimosis)
  • Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions). [This exclusion also applies to therapeutic anticoagulation that results in a prolonged PT/INR or PTT.]
  • HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who received control/placebo in an HIV vaccine trial, the HVTN 914 PSRT will determine eligibility on a case-by-case basis
  • Untreated clinical signs or symptoms of genitourinary or colonic infection
  • Any medical condition contraindicating circumcision or flexible sigmoidoscopy with biopsies
  • History of transactional sex (ie, exchange of sex for money, shelter, food, or drugs) in the preceding 6 months
  • Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, or a participant's ability to give informed consent
  • History of keloid scarring

Treatment and study plan

Circumcision

Procedure

Flexible sigmoidoscopy

Procedure

Primary outcomes

  1. Pre- and post-procedure retention

    Time frame: 28 weeks

    Number of enrolled trial participants that underwent each procedure visit and attended each follow-up visit

  2. White blood cell counts

    Time frame: 28 weeks

    White blood cells per mm^3

  3. Hematocrit

    Time frame: 28 weeks

    Hematocrit values measured as percentage

  4. Hemoglobin

    Time frame: 28 weeks

    Hemoglobin g/dL

  5. Sexual satisfaction

    Time frame: 28 weeks

    Sexual satisfaction during receptive, insertive sex, and abstinence periods using a CASI behavioral questionnaire (5 point Likert Scale)

  6. HIV risk behaviors

    Time frame: 28 weeks

    Sex without a condom according to a CASI behavioral questionnaire (Yes, No)

  7. Levels of activation markers associated with vulnerability to HIV infection

    Time frame: 28 weeks

    Levels of CCR5, ki67+ Bcl2low, and integrin alpha4beta7 expression on CD4+ CD3+ T cells collected in blood

  8. Procedure-related events

    Time frame: 28 weeks

    Number of procedure related events such as adverse drug reactions, hermorrage/hematoma, infection, pain, perforation/anatomic injury, and edema assessed for severity (NIH/NIAID DIvision of AIDS table for Grading of Severity of Adult and Pediatric Adverse Experiences).

  9. Number of operational protocol deviations per mucosal sample

    Time frame: through study completion, an average of 7 months

    Number of deviations per mucosal sample

  10. Proportion of mucosal samples that are evaluable

    Time frame: through study completion, an average of 7 months

    Percent of total samples (%)

  11. Inter-person variability in mucosal responses

    Time frame: 28 weeks

    Median and range of variables in peripheral blood mononuclear cells, foreskin, and rectosigmoid mucosa

  12. Intra-person differences in mucosal responses obtained from the rectosigmoid colon

    Time frame: 28 weeks

    Median and range of variables in peripheral blood mononuclear cells, foreskin, and rectosigmoid mucosa

  13. Number of clinical protocol deviations per mucosal sample

    Time frame: through study completion, an average of 7 months

    Number of deviations per mucosal sample

  14. Number of laboratory protocol deviations per mucosal sample

    Time frame: through study completion, an average of 7 months

    Number of deviations per mucosal sample

Sponsors and collaborators

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Nih

Registry information

Official study title

A Cohort Study in Lima, Peru to Evaluate Feasibility of Measuring Immune Responses & Activation Levels in the Foreskin & Rectosigmoid Mucosa in HIV-negative, Uncircumcised Men Who Have Sex With Men & Who Are at High Risk for HIV Acquisition

Acronym: HVTN 914

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
Dec 15, 2015
Registry last updated
Dec 15, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.