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

University of Melbourne

Status

Completed

Conditions

HIV

Treatments

Other: External Stress Group

Other: Diurnal Variation Group

Study type

Observational

Funder types

Other

Identifiers

NCT02895087

U19AI096109

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

Male

Ages

25 to 55 years old

Volunteers

No Healthy Volunteers

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