Clinical trial NCT00767312: Analysis of HIV-1 Replication During Antiretroviral Therapy
Official title: Analysis of HIV-1 Replication During Antiretroviral Therapy
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: HIV
Keywords: HIV
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2008-10-07
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.

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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.

Eligibility criteria: * 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.

Primary outcomes:
measure: We plan to investigate the relationship of HIV-1 viral RNA levels and genetic variation in patients on antiretroviral therapy over prolonged periods.
timeFrame: every 6 months
Secondary outcomes:
measure: Provide human subjects protection oversight for samples accrued in protocol 97-I-0082 and 00-I-0110
timeFrame: ongoing
measure: Investigate the genetic and immunologic characteristics of patients with HIV-1 suppression on antiretroviral therapy who experience rebound viremia
timeFrame: ongoing
measure: Investigate determinants of HIV-1 DNA quantity and characteristics in suppressed patients
timeFrame: ongoing
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Frank Maldarelli, M.D.
role: PRINCIPAL_INVESTIGATOR
References: