Study to Explore Natural Daily Variation and Impact of Stress in HIV Levels

NCT02895087 | Completed

• 1 other identifier: U19AI096109
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Despite advances in AntiRetroviral Therapy (ART) leading to a rapid control of the HIV virus in individuals affected, HIV can persist indefinitely and there is no cure. The HIV virus has been shown to have a unique ability to hide within the human gene inside human cells and in tissues, remaining 'silent' and rapidly reactivate 'waking up" if ART is stopped. There are a number of ways to measure the silent HIV reservoir, including a common research-based laboratory test called Cell-Associated UnSpliced (CA-US) HIV RNA. This is an early marker of the HIV virus waking up. It is often used to test how well new drugs developed to eliminate the silent virus might work. This study is examining whether the diurnal variation (daily rhythm) and/or stress can affect CA-US HIV RNA levels in individuals diagnosed with HIV and receiving ART.

Conditions

HIV

Keywords

diurnal variation; stress

Outcome Measures

Primary Outcomes (2)

• Diurnal variation effects on HIV transcription

  To determine if there are diurnal variations in cortisol and catecholamine in HIV transcription in latently-infected cells in HIV-infected participants on ART.

  24 hours

• Stress Factor effects on HIV transcription

  To determine the effects of stress-induced changes in cortisol and catecholamine on HIV transcription, in latently infected cells in HIV-infected participants on ART.

  Baseline (visit 1) and visit 2 (approximately 1 - 7 days later)

Study Arms (2)

Cohort 1: Diurnal Variation Group

Cohort recruitment - open to recruitment

Other: Diurnal Variation Group

Cohort 2: External Stress Group

Cohort recruitment - closed to recruitment

Other: External Stress Group

Interventions

Diurnal Variation Group OTHER

This intervention occurs over one 24-hour period. Eligible participants will be required to be admitted into a supervised environment for 24-hours arriving no later than 0730. Blood draws will then be taken every 4 hours (0800, 1200, 1600, 2000, 2400 and 0400). Care will be taken to ensure the total blood draws (including the screening visit) stay within Red Cross Guidelines (less than 500 ml every 8 weeks).

Cohort 1: Diurnal Variation Group

External Stress Group OTHER

2 visits will be required, each lasting approximately 2.5 hours in the afternoon. At both visits participants will rest quietly for 15 minutes, then have 3 blood draws and 4 saliva samples over approximately one hour. Participants will also be required to complete short questionnaires about their mood and experience. At the second visit, participants will also complete some thinking and talking tasks. In addition the autonomic nervous system of the participant's will be monitored throughout the visit.

Cohort 2: External Stress Group

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Cohort 1: Open to study participants who meet the inclusion/exclusion criteria and have been either referred by their health care provider or self-referred to the study team. Cohort 2: Open to study participants who meet the inclusion/exclusion criteria; participants will be primarily drawn from the pool of Options and Scope study participants who have consented to being contacted for future studies

You may qualify if:

• Male
• HIV +
• On suppressive ART \> 3 years
• Undetectable viral load, documented in past 3 months
• English speaking
• Have regular sleeping habits (\~ 6 - 8 hours a night) \[Cohort 1\]
• Do not do shift-work \[Cohort 1\]
• Have not had any transcontinental travel in the last month \[Cohort 1\]

You may not qualify if:

• Known sleep disorder, Addison's disease, diabetes or thyroid/pituitary/adrenal/splenic disorder (note: corrected hypothyroid disorder may be allowed if recent Thyroid Stimulating Hormone (TSH) results are within normal limits);
• Current cancer (radiation, chemo or surgery within past year);
• Recent anemia
• Medications that affect study outcomes, including Automatic Nervous System (ANS) measurement: Use of immunomodulation drugs (e.g. Interleukin 21, prednisone, growth hormone, tacrolimus, methotrexate; or other medications used in autoimmune disorders such as lupus, rheumatoid arthritis, Crohn's disease, MS)
• Steroids including; corticosteroids (including regular use of inhaled/nasal steroids for severe/chronic asthma or allergies), testosterone, or anabolic steroids
• Beta-blockers
• Certain psychiatric medications including regular use of medium or long-acting benzodiazepines or other anxiolytics/sedatives (note: occasional use of short-acting anxiolytics or sleep meds okay);
• Disulfiram or experimental Latent Retroviral Activation (LRA) use
• Psychiatric conditions including current major depression or severe anxiety disorder; bipolar disorder; schizophrenia; current PTSD; or severe Attention Deficit Hyperactivity Disorder (ADHD)
• Alcohol use \> 14 drinks/week, or daily use of any recreational drug other than marijuana (participant must be able abstain from alcohol and recreational drug use the day before and day of study visits)
• BMI\>34.9
• Pacemaker
• General anesthesia in the past month
• Inability to provide informed consent

Sponsors & Collaborators

• University of Melbourne: lead
• University of California, San Francisco: collaborator

Study Sites (2)

Osher Center, University of California San Francisco

San Francisco, California, 94115, United States

Location

Division of Infectious Diseases

Milwaukee, Wisconsin, 53226, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Part 1: Diurnal Variation cohort (total 15 participants) - no longer recruiting Blood samples Part 2: Stress cohort (total 20 participants) - no longer recruiting Blood samples Saliva Samples

Study Officials

• Sharon R Lewin, FRACP, PhD

  The Doherty Institute for Infection and Immunity, Melbourne University

  PRINCIPAL INVESTIGATOR

• Frederick M Hecht, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2016
• First Posted: September 9, 2016
• Study Start: March 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2018
• Last Updated: November 4, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)