HIV-1 Viral Dynamics in Subjects Initiating Raltegravir 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: NCT00709397
Recruitment Status : Terminated (lack of accrual)
First Posted : July 3, 2008
Last Update Posted : August 2, 2010
Merck Sharp & Dohme Corp.
Information provided by:
Brigham and Women's Hospital

Brief Summary:
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 or disease Intervention/treatment
HIV-1 Infection Other: blood drawing

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.

Study Type : Observational
Actual Enrollment : 3 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: HIV-1 Viral Dynamics in Subjects Initiating Raltegravir Therapy
Study Start Date : June 2008
Actual Primary Completion Date : December 2009
Actual Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort Intervention/treatment
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.

Primary Outcome Measures :
  1. first- and second-phase decay rates of plasma HIV-1 RNA [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. 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 ]
  2. 2. Quantify changes in the intracellular levels of HIV-1 proviral DNA and LTR circles during raltegravir therapy. [ Time Frame: 24 weeks ]
  3. 3. Correlate changes in the intracellular DNA compartments with first- and second-phase plasma HIV-1 RNA clearance rates. [ Time Frame: 24 weeks ]

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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

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.

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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): NCT00709397

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.
Principal Investigator: Daniel R Kuritzkes, MD Brigham and Women's Hospital

Responsible Party: Daniel R. Kuritzkes, MD, Brigham and Women's Hospital Identifier: NCT00709397     History of Changes
Other Study ID Numbers: 2007-P-002410/1
First Posted: July 3, 2008    Key Record Dates
Last Update Posted: August 2, 2010
Last Verified: July 2010

Keywords provided by Brigham and Women's Hospital:
drug resistance
integrase inhibitor

Additional relevant MeSH terms:
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action