HIV-1 Viral Dynamics in Subjects Initiating Raltegravir Therapy

This study has been terminated.
(lack of accrual)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00709397
First received: July 1, 2008
Last updated: July 29, 2010
Last verified: July 2010
  Purpose

This study is designed to determine how quickly HIV-1 is cleared from the blood in treatment-experienced patients beginning a salvage therapy regimen that includes the integrase inhibitor raltegravir. The hypothesis is that HIV-1 is cleared as rapidly in these patients as in treatment-naive patients starting a raltegravir-based regimen.


Condition Intervention
HIV-1 Infection
Other: blood drawing

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: HIV-1 Viral Dynamics in Subjects Initiating Raltegravir Therapy

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • first- and second-phase decay rates of plasma HIV-1 RNA [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1. As exploratory analyses, to compare the observed first-phase decay rate of plasma HIV-1 RNA in treatment-experienced patients receiving raltegravir to treatment-naïve patients in other studies. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 2. Quantify changes in the intracellular levels of HIV-1 proviral DNA and LTR circles during raltegravir therapy. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 3. Correlate changes in the intracellular DNA compartments with first- and second-phase plasma HIV-1 RNA clearance rates. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Peripheral blood mononuclear cells will be tested for HIV-1 DNA levels. The cell pellets obtained from each of the samples will be tested for 1) total HIV-1 DNA and 2-LTR circles using real-time quantitative PCR and 2) integrated proviral DNA using Alu real-time nested PCR.


Enrollment: 3
Study Start Date: June 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Observation
antiretroviral-experienced patients requiring raltegravir to construct an adequately potent antiretroviral regimen.
Other: blood drawing
Subjects will have been prescribed raltegravir (400 mg BID) by their primary physicians. Such subjects will have frequent blood sampling in this study to monitor the virologic response to raltegravir therapy.

Detailed Description:

This pilot study will closely examine the viral dynamics of both HIV-1 RNA and DNA in treatment-experienced subjects initiating raltegravir. The data derived from this study will further elucidate the effects of antiviral therapy on viral decay and help refine current viral dynamics models. In addition, results of this study will generate hypotheses for further testing regarding the mechanisms of action of integrase inhibitor therapy in salvage regimens. Lastly, this viral dynamic study on a unique cohort will provide an opportunity to further validate the effectiveness of the methods of measuring rate of decrease of viral RNA and DNA in piloting potential potent drug regimens.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Eligible subjects are antiretroviral-experienced patients requiring raltegravir to construct an adequately potent antiretroviral regimen.

Criteria

Inclusion Criteria:

  • HIV-infected patients age 18 years or older requiring treatment with raltegravir in order to construct an adequately active antiretroviral regimen.
  • Availability of at least two other drugs expected to have full activity based on genotypic and/or phenotypic drug resistance testing, a co-receptor tropism assay, or first use of a drug from a previously unused class of antiretroviral drugs (e.g., first use of enfuvirtide).
  • Plasma HIV-1 RNA >10,000 copies/mL at screening (within 6 weeks of study entry).
  • Negative serum or urine pregnancy test at screening and within 48 hours prior to entry for women with reproductive potential
  • Ability and willingness of subject or legal guardian/representative to provide informed consent.

Exclusion Criteria:

  • Pregnancy or breast-feeding.
  • Previous treatment with any approved or investigational strand-transfer integrase inhibitor at any time prior to study entry.
  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
  • Any subject with an acute AIDS-defining opportunistic infection (OI) who is not clinically stable or who has not been on therapy for the OI for at least 30 days prior to study entry. Subjects who have no evidence of active disease and are receiving maintenance therapy for AIDS-related OIs will be eligible.
  • Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy.

NOTE: Subjects receiving stable physiologic glucocorticoid doses, defined as prednisone ≤ 10 mg/day (or equivalent) as a stable or tapering dose, will be permitted. Subjects receiving corticosteroids for acute therapy forPneumocystis jaroveci pneumonia (PCP) or asthma exacerbation, or receiving a short course (defined as ≤ 2 weeks of pharmacologic glucocorticoid therapy) will not be excluded.

• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.

NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction.

• Substance abuse that, in the opinion of the site investigator, would interfere with adherence to study requirements.who have limited or no treatment options due to extensive antiretroviral drug resistance or drug intolerance.

  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: NCT00709397

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Daniel R Kuritzkes, MD Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Daniel R. Kuritzkes, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00709397     History of Changes
Other Study ID Numbers: 2007-P-002410/1
Study First Received: July 1, 2008
Last Updated: July 29, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
HIV-1
drug resistance
raltegravir
integrase inhibitor

ClinicalTrials.gov processed this record on October 01, 2014