Analysis of HIV-1 Replication During Antiretroviral Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00767312
Recruitment Status : Enrolling by invitation
First Posted : October 7, 2008
Last Update Posted : March 29, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

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.

Condition or disease
HIV Infection

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
Actual Enrollment : 43 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Analysis of HIV-1 Replication During Antiretroviral Therapy
Study Start Date : October 1, 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Primary Outcome Measures :
  1. We plan to investigate the relationship of HIV-1 viral RNA levels and genetic variation in patients on antiretroviral therapy over prolonged periods. [ Time Frame: End of Study ]

Secondary Outcome Measures :
  1. 1. Investigate the determinants of HIV- 1 viremia in suppressed patients [ Time Frame: End of Study ]
  2. 3. Investigate the genetic and immunologic characteristics of patients with HIV-1 suppression on antiretroviral therapy who experience rebound viremia [ Time Frame: End of Study ]
  3. 2. Provide human subjects protection oversight for samples accrued in protocol 97-I-0082 and 00-I-0110 [ Time Frame: End of Study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00767312

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Frank Maldarelli, M.D. National Cancer Institute (NCI)

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00767312     History of Changes
Other Study ID Numbers: 080221
First Posted: October 7, 2008    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: December 19, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Antiretrovial Therapy
Genetic Analysis
Single Copy Assay

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases