Mapping the Human HIV Chronobiome (HCB)

Mapping the Human Immunodeficiency Virus Chronobiome, (HIV)

Individuals infected with HIV have a high risk of developing metabolic comorbidities not traditionally associated with the immune dysregulation and deficiency associated with HIV infection and AIDS. Many of these comorbidities in HIV uninfected individuals have been linked to a disordered circadian clock function. The study investigators will further evaluate the circadian clock in HIV infection as a mechanism underlying the metabolic dysregulation in this population.

Study Overview

• Status: Suspended
• Conditions: Healthy; Hiv
• Intervention / Treatment: Other: Observational

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Cohort 1: patients infected with HIV off antiretroviral therapy;

Cohort 2: patients infected with HIV experiencing virologic control, but with blunted immunologic recovery;

Cohort 3: matched healthy volunteers.

Description

Inclusion Criteria:

• Cohort 1: Diagnosis of HIV infection with CD4+ counts <500 cells/mm3 while untreated;
• Cohort 2: Diagnosis of HIV infection with CD4+ counts <300 cells/mm3 on ARV;
• Cohort 3: Volunteers must be in good health as based on medical history, physical examination, vital signs, and laboratory tests as deemed by PI;
• Volunteers are capable of giving informed consent;
• 25-50 years of age;
• Own a smartphone which installs the remote sensing applications;
• Non-smoking;
• Male subjects only if feasible during recruitment; and
• In case female volunteers are invited to enroll: non-pregnant, female subjects must consent to a urine pregnancy test.
• Females of child bearing potential will be asked to use a medically accepted method of birth control (such as oral contraceptives, intra-uterine device (IUD), or condom with spermicide) while you participate in the study.
• The use of contraception will NOT be required for male participants.

Exclusion Criteria:

• Recent travel across more than two (2) time zones (within the past month);
• Planned travel across more than two (2) time zones during the planned study activities;
• Volunteers with irregular work hours, e.g. night shifts or becoming a parent;
• Use of illicit drugs;
• High dose vitamins (Vitamin A, Vitamin C, Vitamin E, Beta Carotene, Folic Acid and Selenium), alcohol and any over-the counter NSAID in the (2) two weeks before the start of the 48 hour deep phenotyping period (Females who are taking birth control pills can continue so for the duration of this study).;
• History of abdominal surgery;
• Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening;
• Subjects with any abnormal laboratory value or physical finding that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject.
• Women who are breastfeeding.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; Patients infected with HIV off antiretroviral therapy	Other: Observational; We will use a deep phenotyping approach to collect multidimensional datasets from individuals infected with HIV compared to healthy controls to define circadian rhythm disruptions associated with HIV infection.
Cohort 2; Patients infected with HIV experiencing virologic control, but with blunted immunologic recovery	Other: Observational; We will use a deep phenotyping approach to collect multidimensional datasets from individuals infected with HIV compared to healthy controls to define circadian rhythm disruptions associated with HIV infection.
Cohort 3; Matched healthy volunteers	Other: Observational; We will use a deep phenotyping approach to collect multidimensional datasets from individuals infected with HIV compared to healthy controls to define circadian rhythm disruptions associated with HIV infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-of-day fluctuations in core clock gene expression	Relative expression normalized to housekeeping genes (GAPDH, ACTB) plotted by time of day (morning, afternoon, evening, night with target times of 08:00, 14:00, 20:00, 02:00 +/- 1 hour)	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variance explained [R^2 values]	To evaluate the linear relationships between every pairwise combination of variables in the integrated dataset, the R^2, or coefficient of determination, will be calculated for each pair using linear regression. A heat map of the proportion of variance in each variable (e.g. mobility, light exposure, systolic blood pressure) explained by each other variable will then be constructed to allow an integrative exploration of these data. This approach allows to integrate multiple measurements with different units of measure. The measurements include communication (number of phone calls and text messages), mobility (miles traveled), light exposure, blood pressure, heart rate, heart rate variability, sleep/wake times, body core temperature, multiomics outputs (abundance of metabolites, proteins, microbiota) and markers of cellular and inflammatory function and disease state (HIV infection).	48 hours
Variance explained [R^2 values]	To evaluate the linear relationships between every pairwise combination of variables in the integrated dataset, the R^2, or coefficient of determination, will be calculated for each pair using linear regression. A heat map of the proportion of variance in each variable (e.g. mobility, light exposure, systolic blood pressure) explained by each other variable will then be constructed to allow an integrative exploration of these data. This approach allows to integrate multiple measurements with different units of measure. The measurements include communication (number of phone calls and text messages), mobility (miles traveled), light exposure, and sleep/wake times.	up to 4 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Carsten Skarke, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2017
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: December 21, 2016
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Health Services Administration; Quality of Health Care; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Watchful Waiting
• Other Study ID Numbers: 825626

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: To be determined