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

NCT ID: NCT02895087

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2018-01-31

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.

Detailed Description

Undetectable or low circulating levels of HIV virus in blood are the result of people who have been diagnosed with a HIV-infection and who have adhered to a HIV AntiRetroviral Therapy (ART) regimen. However, the ART has not eradicated the virus from the body and individuals who cease ART can rapidly revert from a well-controlled state to showing high levels of HIV virus in the blood. 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 [or wake up] if ART is stopped. Efforts are underway to explore novel ways to entirely eradicate HIV from individuals, so that people who are HIV-infected can stop treatment and still have undetectable HIV viral load and remain well despite not being on HIV treatment.

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 reactivating. It is often used to test how well new drugs developed to eliminate the silent virus might work.

Recently as investigators involved in another clinical study, an unexpected observation was noted in a group of HIV study participants on ART between the CA-US HIV RNA levels and time of blood collection. Levels of CA-US HIV RNA appeared to be lower when blood samples were collected earlier in the morning. However, at the time of this observation, as investigators were unable to establish whether this discrepancy could be due to (i) the diurnal variation or (ii) unknown stress factors that may have been experienced by the study participants. It has previously been demonstrated that individuals with untreated HIV infection there is a variation in HIV RNA levels and the time of day. However, the effects of external factors such as time of day or stresses on CA-US HIV RNA levels in individuals while on ART have not been previously examined.

This study hopes to explore and answer the questions (i) Does the diurnal variation play a role in regulating the levels of CA-US HIV RNA in blood of individuals diagnosed with HIV and receiving ART and (ii) Does stress affect the levels of CA-US HIV RNA.

Understanding some factors that affect levels of CA-US HIV RNA may provide a new perspective on ways to eliminate the silent virus.

Conditions

HIV

Keywords

diurnal variation; stress

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cohort 1: Diurnal Variation Group

Cohort recruitment - open to recruitment

Diurnal Variation Group

Intervention Type: 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 2: External Stress Group

Cohort recruitment - closed to recruitment

External Stress Group

Intervention Type: 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.

Interventions

Diurnal Variation Group

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).

Intervention Type: OTHER

External Stress Group

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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]

Exclusion Criteria

• 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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: collaborator

University of Melbourne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sharon R Lewin, FRACP, PhD

Role: PRINCIPAL_INVESTIGATOR

The Doherty Institute for Infection and Immunity, Melbourne University

Frederick M Hecht, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Osher Center, University of California San Francisco

San Francisco, California, United States

Division of Infectious Diseases

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

U19AI096109

Identifier Type: NIH

Identifier Source: org_study_id

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