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

Not Applicable

Completed

• Conditions: RNA Virus Infections; Acquired Immunodeficiency Syndrome; Sexually Transmitted Diseases; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Lentivirus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral
• Interventions: Procedure: Circumcision; Procedure: Flexible sigmoidoscopy

• Registration Number: NCT02630082
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2011-04
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Study First Submitted: 2015-08-24
• Status Verified: 2015-12
• Study First Submitted QC: 2015-12-10
• Last Update Submitted: 2015-12-10
• Study First Posted: 2015-12-15
• Last Update Posted: 2015-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 29

Inclusion Criteria

1. 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.

2. Ability and willingness to provide informed consent

3. 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.

4. Willingness to receive HIV test results

5. Willingness to discuss HIV infection risks (including sexual behavior and drug use) and amenable to HIV risk reduction counseling

6. Willingness to undergo phlebotomy, rectal swab, sigmoidoscopy, and circumcision

7. Willingness to adhere to safety protocols before and after sigmoidoscopy and circumcision

8. Agrees not to enroll in another study of an investigational research agent prior to completion of the last required protocol clinic visit

9. Hemoglobin ≥ 13.0 g/dL

10. White blood cell (WBC) count = 3300 to 12,000 cells/mm3

11. Total lymphocyte count ≥ 800 cells/mm3

12. Remaining differential either within institutional normal range or with site physician approval

13. Platelets = 125,000 to 550,000/mm3

14. Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.25 institutional upper limit of normal; International Normalized Ratio (INR) ≤ 1.5

15. Negative HIV-1 and -2 blood test: May use locally available assays that have been approved by HVTN Laboratory Operations.

Exclusion Criteria

1. Volunteers who, in the six months prior to screening, have had sexual partners known to be HIV-infected
2. Volunteers who, for the 6 months prior to screening, have been in a monogamous relationship with an HIV-seronegative partner
3. History of immunodeficiency
4. Foreskin covering less than half the glans
5. Absolute medical indication for circumcision (balanitis or phimosis)
6. 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.]
7. 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
8. Untreated clinical signs or symptoms of genitourinary or colonic infection
9. Any medical condition contraindicating circumcision or flexible sigmoidoscopy with biopsies
10. History of transactional sex (ie, exchange of sex for money, shelter, food, or drugs) in the preceding 6 months
11. 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
12. History of keloid scarring

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Flexible sigmoidoscopy	Circumcision and flexible sigmoidoscopy
Intervention	Circumcision	Circumcision and flexible sigmoidoscopy

Primary Outcome Measures

Name	Time	Method
Hematocrit	28 weeks	Hematocrit values measured as percentage
Hemoglobin	28 weeks	Hemoglobin g/dL
Levels of activation markers associated with vulnerability to HIV infection	28 weeks	Levels of CCR5, ki67+ Bcl2low, and integrin alpha4beta7 expression on CD4+ CD3+ T cells collected in blood
Number of operational protocol deviations per mucosal sample	through study completion, an average of 7 months	Number of deviations per mucosal sample
Proportion of mucosal samples that are evaluable	through study completion, an average of 7 months	Percent of total samples (%)
Pre- and post-procedure retention	28 weeks	Number of enrolled trial participants that underwent each procedure visit and attended each follow-up visit
White blood cell counts	28 weeks	White blood cells per mm\^3
Sexual satisfaction	28 weeks	Sexual satisfaction during receptive, insertive sex, and abstinence periods using a CASI behavioral questionnaire (5 point Likert Scale)
HIV risk behaviors	28 weeks	Sex without a condom according to a CASI behavioral questionnaire (Yes, No)
Procedure-related events	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).
Inter-person variability in mucosal responses	28 weeks	Median and range of variables in peripheral blood mononuclear cells, foreskin, and rectosigmoid mucosa
Intra-person differences in mucosal responses obtained from the rectosigmoid colon	28 weeks	Median and range of variables in peripheral blood mononuclear cells, foreskin, and rectosigmoid mucosa
Number of clinical protocol deviations per mucosal sample	through study completion, an average of 7 months	Number of deviations per mucosal sample
Number of laboratory protocol deviations per mucosal sample	through study completion, an average of 7 months	Number of deviations per mucosal sample