Clinical trial NCT02985996: Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities
Official title: Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Preventative Medicine
Infectious Diseases
Sexually Transmitted Diseases
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2016-12-07
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine the ability of new anti-HIV agents to penetrate different body compartments in HIV negative men who have sex with men and transgender women. These new agents might be considered for pre-exposure prophylaxis regimens in the future. This study will include 90 healthy, HIV-negative men who have sex with men and transgender women who are not taking hormones aged 18-49 years. Participant must be willing to participate in 1 of the 3 study phases, be willing to take Truvada® (PrEP) or Genvoya®, and willing to undergo blood draws, urethral swabs, and rectal biopsy procedures.

Detailed description: Men who have sex with men (MSM) and Transgender women (TGW) who have sex with men continue to be disproportionately affected by HIV. Over 60% of new HIV infections in the US occur among MSM. The majority of HIV infections among MSM and TGW occur through exposure to the rectal mucosa during receptive anal intercourse (RAI). Pre-exposure prophylaxis (PrEP) is a new HIV prevention method that is recommended by CDC and WHO for MSM at risk of HIV infection. PrEP entails taking an anti-HIV medication (Truvada®; tenofovir/emtricitabine) on a daily basis to prevent HIV infection. However, current tenofovir- based regimens have shown to have side effects that researchers are hoping to reduce in newly developed anti-HIV agents. This study is designed to examine the ability of these new agents to penetrate mucosal tissues and potentially prevent HIV infection during RAI exposure for MSM and TGW.

Eligibility criteria: Inclusion Criteria:

* HIV-negative man who reports receptive anal sex with another man in the last 6 months
* Male to female transgender women who have sex with men who report receptive anal intercourse with another man in the last 6 months and are not currently taking hormonal therapy or plan to take hormonal therapy for the duration of the study
* Not currently taking PrEP and no plans to initiate during study
* Able to provide informed consent in English
* No plans for relocation in the next 3 months
* Willing to undergo peripheral blood and rectal biopsy sampling
* Willing to use study products as directed
* Willing to abstain from receptive anal intercourse 3 days prior to starting study product and for the duration of the study and for 7 days after any rectal biopsy procedure.

Exclusion Criteria:

* History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel
* Significant laboratory abnormalities at baseline visit, including but not limited to:

  1. Hgb ≤ 10 g/dL
  2. PTT \> 1.5x ULN or INR \> 1.5x ULN
  3. Platelet count \<100,000
  4. Creatinine clearance \<60
* Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:

  1. Uncontrolled or severe cardiac arrhythmia
  2. Recent major abdominal, cardiothoracic, or neurological surgery
  3. History of uncontrolled bleeding diathesis
  4. History of colonic, rectal, or vaginal perforation, fistula, or malignancy
  5. History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal or vaginal mucosa, or untreated sexually transmitted disease with mucosal involvement
* Continued need for, or use during the 14 days prior to enrollment, of the following medications:

  1. Aspirin or more than 4 doses of NSAIDs
  2. Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
  3. Any form of rectally administered agent besides products lubricants or douching used for sexual intercourse
* Continued need for, or use during the 90 days prior to enrollment, of the following medications:

  1. Systemic immunomodulatory agents
  2. Supraphysiologic doses of steroids
  3. Experimental medications, vaccines, or biologicals
* Intent to use HIV antiretroviral pre-exposure prophylaxis (PrEP) during the study, outside of the study procedures
* Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)
* Current use of hormonal therapy
* Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.

Primary outcomes:
measure: Changes in Intracellular Emtricitabine Triphosphate (FTC-TP)
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Changes in Intracellular Tenofovir Diphosphate (TFV-DP)
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
Secondary outcomes:
measure: Change in Plasma Emtricitabine (FTC) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Plasma Tenofovir Disoproxil Fumarate (TDF) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Plasma Tenofovir Alafenamide (TAF) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Plasma Elvitegravir (EVG) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Rectal Emtricitabine (FTC) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Rectal Tenofovir Disoproxil Fumarate (TDF) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Rectal Tenofovir Alafenamide (TAF) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Rectal Elvitegravir (EVG) Concentration
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Intracellular Tenofovir Alafenamide (TAF) Concentration in Peripheral Blood Mononuclear Cells (PBMCs)
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Intracellular Elvitegravir (EVG) Concentration in Peripheral Blood Mononuclear Cells (PBMCs)
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Intracellular Emtricitabine (FTC) Concentration in Rectal Tissue
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Intracellular Tenofovir (TFV) Concentration in Rectal Tissue
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Tenofovir Alafenamide (TAF) Concentration in Rectal Tissue
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Elvitegravir (EVG) Concentration in Rectal Tissue
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Emtricitabine (FTC) Concentration in Penile Secretions
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Tenofovir Disoproxil Fumarate (TDF) Concentration in Penile Secretions
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Tenofovir Alafenamide (TAF) Concentration in Penile Secretions
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: Change in Elvitegravir (EVG) Concentration in Penile Secretions
timeFrame: Baseline, Visit 4 (Up to ten days post drug)
measure: PrEP Efficacy as Measured by Inhibition of in Vitro Infection of Rectal Biopsies to HIV
timeFrame: Up to 10 months post-baseline
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Colleen Kelley, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: