HIV-1 Viral Dynamics in Subjects Initiating Raltegravir Therapy

NCT00709397 | Terminated

• 1 other identifier: 2007-P-002410/1
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV-1 Infection

Keywords

HIV-1; drug resistance; raltegravir; integrase inhibitor

Outcome Measures

Primary Outcomes (1)

• first- and second-phase decay rates of plasma HIV-1 RNA

  24 weeks

Secondary Outcomes (3)

• 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.

  24 weeks

• 2. Quantify changes in the intracellular levels of HIV-1 proviral DNA and LTR circles during raltegravir therapy.

  24 weeks

• 3. Correlate changes in the intracellular DNA compartments with first- and second-phase plasma HIV-1 RNA clearance rates.

  24 weeks

Study Arms (1)

Observation

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

Other: blood drawing

Interventions

blood drawing OTHER

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.

Observation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

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.

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Daniel R Kuritzkes, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 3, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 2, 2010

Record last verified: 2010-07

Locations

US (2)