This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Quantitative Measurement and Correlates of the Latent HIV Reservoir in Virally Suppressed Ugandans

This study is currently recruiting participants.
See Contacts and Locations
Verified March 28, 2017 by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT02154035
First received: May 31, 2014
Last updated: April 21, 2017
Last verified: March 28, 2017
  Purpose

Background:

Human Immunodeficiency Virus (HIV) is the virus that causes AIDS. HIV can hide in the blood for many years, even in people who have their HIV infection under control. HIV that is hiding in the blood is called the latent HIV reservoir. Researchers want to find out more about it in this study. This knowledge may help them develop new ways to prevent or control HIV. This study will draw its participants from the Rakai Health Sciences Program in rural southwestern Uganda.

Objective:

- To measure and learn about the latent HIV reservoir in Ugandans with HIV.

Eligibility:

- Men and women at least 18 years of age with HIV.

Design:

  • Participants will have a medical history and physical exam. Their medical records will be reviewed. Researchers will ask participants about their health and recent illnesses. Participants able to get pregnant will have their urine tested for pregnancy.
  • Participants will have their finger pricked to see if they have enough red blood cells to be eligible for the study.
  • If eligible, participants will have blood drawn through a needle in the arm. Their blood will also be tested for other diseases.
  • After the blood draw, participants will be asked to stay seated or lying down if they are not feeling well for up to 30 minutes.

Condition
HIV

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Other
Official Title: Quantitative Measurement and Correlates of the Latent HIV Reservoir in Virally Suppressed Ugandans

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):

Primary Outcome Measures:
  • Examine and measure the levels of latent HIV reservoirs in virally suppressed Ugandans and compare to that observed in Western (US) cohorts [ Time Frame: Enrollment ]
  • Determine the role of endemic infectious diseases, nadir CD4 count, and length of fully suppressive therapy on latent HIV reservoir size [ Time Frame: Enrollment ]
  • Explore the level of immune activation in virally suppressed HIV-infected Africans in correlation with the size of the reservoir [ Time Frame: Enrollment ]

Estimated Enrollment: 120
Study Start Date: May 19, 2014
Estimated Study Completion Date: December 31, 2019
Estimated Primary Completion Date: March 31, 2018 (Final data collection date for primary outcome measure)
Detailed Description:

Despite prolonged antiretroviral therapy (ART), HIV-1 can persist as transcriptionally inactive proviruses in resting memory CD4+T cells. This latent reservoir has a long half-life, and is believed to be the largest impediment to a cure by ART alone. The latent reservoir may be established when activated CD4+ T cells become infected and subsequently revert back to a resting memory state. A major approach to eradicating HIV-1 involves reversing latency in patients on ART. Cells harboring induced proviruses could be lysed by HIV-1-specific cytolytic T lymphocytes, while ART blocks new rounds of infection. The descriptions of the Berlin patient and Mississippi baby suggest that a functional cure for HIV is possible. This has led to an expansion of research examining HIV latency in the context of sustained viral suppression with an eye towards developing a possible cure regimen that could be used on a large scale. However, it has recently been demonstrated that the latent HIV reservoir could be 60 times larger than previously believed. The recent report that two HIV patients receiving CCR5-competent bone marrow transplants had a reemergence of circulating HIV after fully suppressive therapy was discontinued suggests that a functional cure for large groups of individuals will continue to be an elusive goal.

The vast majority of HIV-infected individuals currently live in sub-Saharan Africa where fully suppressive ART is expanding rapidly. Due to this expansion, a large number of Africans will be eligible candidates for cure treatment when one comes available. However, strategies needed to establish a functional cure may differ in African populations due to differences in endemic infectious disease load and in cellular immune activation among Africans as compared to Western populations. To date, there have been no systematic studies to quantify the latent reservoir in HIV-infected Africans. This is a longitudinal, descriptive study to measure the size of the latent HIV reservoir in virally suppressed HIV-infected individuals residing in Uganda and to examine the immunological and virologic correlates of the latent reservoir. The study will draw its participants from a National Institutes of Health (NIH) International Center for Excellence in Research (ICER) site, located at the Rakai Health Sciences Program (RHSP) in rural southwestern Uganda. One group of subjects will be comprised of 90 HIV-infected patients who are on ART with suppressed viral loads <40 copies per ml over a period of 10-18 months, including 20 individuals with a known window of seroconversion (an HIV-negative test result no more than 18 months before the first HIV-positive test result). A second group will be comprised of 10 HIV-infected subjects with suppressed viral load <40 copies per ml over a period of 10-18 months. Study participation will require a visit with a finger stick hemoglobin screening and a blood draw, once a year for a period of three years. Plasma and cells from the blood will be separated and processed for quantitative viral latency, circulating cytokine and chemokine analysis, co-culture, and flow cytometric and serologic assays for selected immunological parameters. Viral latency results will be compared within each individual for changes in the reservoir size that might occur over three years of continual viral suppression in order to calculate the T 1/2 or decay rate of the latent reservoir. Samples collected from individuals with known infection dates will be used to estimate

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. At least 18 years of age
    2. Hemoglobin >9g/dL as assessed by fingerstick rapid test
    3. A historical diagnosis of HIV infection as indicated by any positive serological test (ELISA, HIV rapid test, or Western Blot)
    4. Virally suppressed as defined as at least two historical viral loads <40 copies/ml obtained between 10 18 months apart, and no intervening detectable viral load result >= 40 copies/ml obtained during this period
    5. Most recent historical viral load result obtained within a year prior to the screening visit
    6. Willingness to undergo genetic testing

EXCLUSION CRITERIA:

  1. Women who are pregnant will be excluded as the required blood draw may cause anemia
  2. Inability to follow study instructions or to provide informed consent
  3. Any condition deemed by the investigators to be a contraindication to study participation including active, serious infections (other than HIV infection) during the 2 weeks prior to enrollment
  4. Malignancies of any kind (e.g., Kaposi's sarcoma)
  5. Therapy with systemic steroids, immunosuppressants or immunomodulating agents
  6. Coagulation defects or other serious bleeding disorders
  7. Current use of medications which could affect clotting
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02154035

Contacts
Contact: Kevin O Newell (301) 846-5365 newellk@mail.nih.gov
Contact: Thomas C Quinn, M.D. (410) 955-7635 tquinn@jhmi.edu

Locations
Uganda
Rakai Health Sciences Program Uganda Virus Research Institute Recruiting
Kalisizo, Uganda
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Thomas C Quinn, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02154035     History of Changes
Other Study ID Numbers: 999914123
14-I-N123
Study First Received: May 31, 2014
Last Updated: April 21, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Viral Suppression
Functional Cure

ClinicalTrials.gov processed this record on June 26, 2017