Analysis of HIV-1 Replication During Antiretroviral Therapy

This study will determine if the level of virus in HIV-infected patients taking antiretroviral medications for prolonged periods decreases or persists at a stable level. It will also examine whether new gene changes (mutations) occur during drug suppression.

HIV-infected patients who are 18 years of age or older, have been enrolled in another NIH protocol, have been suppressed on antiretroviral therapy and have very low levels of virus in their blood may be eligible for this 5-year (or more) study.

Participants come to the NIH Clinical Center about every 6 months for a physical examination, routine and research blood tests and leukapheresis to collect white blood cells for T cell analysis. For leukapheresis, blood is collected through a vein much like donating whole blood, but the blood is directed through a machine that separates and extracts the white cells and returns the rest of the blood components to the patient. Patients may also have an optional third clinic visit each year for another blood draw.

Study Overview

• Status: Enrolling by invitation
• Conditions: HIV

Detailed Description

Combination antiretroviral therapy for human immunodeficiency virus serotype 1 (HIV-1) infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. How drug resistance emerges during suppressive antiretroviral therapy remains poorly understood. Investigating the characteristics of HIV-1 replication during suppressive antiretroviral therapy will yield important insights in understanding the emergence resistance, and requires patients who have suppressed viral RNA levels. Prior National Institutes of Health (NIH) protocols have made important observations regarding the kinetics of HIV-1 decline in response to therapy, the levels of HIV-1 viremia during suppressive therapy, and the nature of HIV-1 genetic diversity prior to and following initiation of antiretroviral therapy. In the process, these studies have generated a useful cohort of patients with suppressed viral RNA levels, who have been extensively characterized from a virologic and immunologic standpoint. Similarly, patients from other NIH protocols have been followed for prolonged periods before and after therapy has been initiated, and they also have stored sample sets that would be useful in new studies of HIV replication. The HIV Drug Resistance Program (DRP) has studied samples from protocols 00-I-0110 and 97-I-0082 to develop a number of new, sensitive laboratory techniques to measure and quantitate genetic variation and to investigate immune response parameters. To further advance understanding of HIV-1 replication during suppressive antiretroviral therapy and the emergence of drug resistance, we propose a new protocol to study these 2 patient cohorts (from the above cited protocols) and selected patients in other protocols with a new series of studies. The primary objective of this protocol is to investigate the virologic and immunologic characteristics of HIV-infected individuals undergoing antiretroviral therapy. Upon implementation, this new protocol will provide human subjects protection for samples collected under the two prior protocols, whether patients enroll in the new study or not.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients from studies: 00-I-0110 and 97-I-0082 are eligible for enrollment. Patients in other NIH studies would be considered for co-enrollment in this study if continued longitudinal sample acquisition is deemed desirable.

Description

• INCLUSION CRITERIA:

Inclusion criteria for this protocol comprise all of the following conditions:

• Age greater than or equal to 18 years.
• HIV infection with documented reactive ELISA and positive western blot.

• Prior enrollment in 00-I-0110, 97-I-0082 OR patients with long term evaluation at NIH for whom additional sampling will be useful for protocol objectives, including:

  • Available stored specimens from pretherapy period.
  • Ongoing suppression of viremia with bDNA less than 50 copies/mL, OR
  • Suppression of viremia to less than 50 copies/mL followed by rebound viremia during therapy.
• Patients must have a private physician for routine medical care.

EXCLUSION CRITERIA:

Any prospective study subject who has been previously withdrawn from any prior study for inability to comply with study procedures will be considered ineligible for this study.

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients; HIV-infected patients who are 18 years of age or older, have been enrolled in another NIH protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
We plan to investigate the relationship of HIV-1 viral RNA levels and genetic variation in patients on antiretroviral therapy over prolonged periods.	HIV-1 viral RNA	every 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Provide human subjects protection oversight for samples accrued in protocol 97-I-0082 and 00-I-0110	protection	ongoing
Investigate the genetic and immunologic characteristics of patients with HIV-1 suppression on antiretroviral therapy who experience rebound viremia	genetic and immunologic	ongoing
Investigate determinants of HIV-1 DNA quantity and characteristics in suppressed patients	HIV DNA quantity and characteristics	ongoing

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Frank Maldarelli, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2008

Study Registration Dates

• First Submitted: October 6, 2008
• First Submitted That Met QC Criteria: October 6, 2008
• First Posted (Estimated): October 7, 2008

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: February 9, 2024

More Information

Terms related to this study

• Keywords: HIV; Natural History
• Other Study ID Numbers: 080221; 08-I-0221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .Identified data in BTRIS (automatic for activities in the Clinical Center).@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements.
• IPD Sharing Time Frame: Identified data in BTRIS (automatic for activities in the Clinical Center and will be available for use following the BTRIS Policy for Data Sharing and Use).
• IPD Sharing Access Criteria: Identified data in BTRIS (automatic for activities in the Clinical Center and will be available for use following the BTRIS Policy for Data Sharing and Use).@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No