Clinical trial NCT00709397: HIV-1 Viral Dynamics in Subjects Initiating Raltegravir Therapy
Official title: HIV-1 Viral Dynamics in Subjects Initiating Raltegravir Therapy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: HIV-1 Infection
Keywords: HIV-1
drug resistance
raltegravir
integrase inhibitor
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-07-03
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible subjects are antiretroviral-experienced patients requiring raltegravir to construct an adequately potent antiretroviral regimen.

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.

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 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.

Primary outcomes:
measure: first- and second-phase decay rates of plasma HIV-1 RNA
timeFrame: 24 weeks
Secondary outcomes:
measure: 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.
timeFrame: 24 weeks
measure: 2. Quantify changes in the intracellular levels of HIV-1 proviral DNA and LTR circles during raltegravir therapy.
timeFrame: 24 weeks
measure: 3. Correlate changes in the intracellular DNA compartments with first- and second-phase plasma HIV-1 RNA clearance rates.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Daniel R Kuritzkes, MD
role: PRINCIPAL_INVESTIGATOR
References: