Raltegravir (Isentress/MK-0518) and HIV-1 Infected CD4 Cells During Acute/Early HIV-1 (UW PIC 330)

Impact of Raltegravir (Isentress/MK-0518) - Containing Regimens on HIV-1 Infected CD4+ T-Cells During Acute and Early HIV-1 Infection: A Randomized, Controlled Study Comparing Standard Antiretroviral Therapy to Standard Therapy Plus Raltegravir

This is an investigator-initiated, two-year, randomized, controlled, single-center, open-label, pilot study comparing 3-drug highly active antiretroviral therapy (HAART) to 3-drug HAART plus raltegravir for persons with acute and early HIV-1 infection. The study will test the hypothesis that use of the integrase inhibitor raltegravir (400 mg BID orally) to inhibit the integration step of the HIV-1 life cycle in conjunction with HAART in subjects with recently acquired HIV-1 infection will decrease the number of HIV-1 infected CD4+ T-cells to a greater extent than a 3-drug HAART regimen.

Study Overview

• Status: Terminated
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Drug: 3-drug anti-HIV therapy; Drug: Raltegravir

Detailed Description

The study will be conducted at the UW Primary Infection Clinic and the UW AIDS Clinical Trials Unit. Secondary objectives will characterize safety, tolerability, plasma HIV-1 RNA and CD4+ T-cell values. The 3-drug HAART will be chosen and provided by the subject.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Primary Infection Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute or Early HIV-1 infection
• HIV-1 RNA > or equal to 500 copies/mL
• Acceptable safety lab results (specified in protocol)
• Negative pregnancy test for females
• Willingness to use contraception (for females of reproductive potential

Exclusion Criteria:

• Prior receipt of investigational HIV-1 vaccine
• Use of immunomodulators other than systemic steroids within 30 days before entry
• Serious medical or psychiatric illness that would interfere with study participation
• Active drug or alcohol use that would interfere with study participation
• Allergy/hypersensitivity to raltegravir
• Pre- or Post-exposure prophylaxis for the exposure that led to HIV-1 acquisition
• Pregnancy or breastfeeding
• History of malignancy (other than localized squamous cell or basal cell cancer of the skin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir + 3-drug anti-HIV therapy	Drug: 3-drug anti-HIV therapy; 3 FDA-approved drugs, including two nucleos(t)ide reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor (Low dose ritonavir can be used to enhance the protease inhibitor and is not considered one of the 3 anti-HIV drugs); Drug: Raltegravir; 400 mg BID PO; Other Names: Isentress
Active Comparator: 3-drug anti-HIV therapy	Drug: 3-drug anti-HIV therapy; 3 FDA-approved drugs, including two nucleos(t)ide reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor (Low dose ritonavir can be used to enhance the protease inhibitor and is not considered one of the 3 anti-HIV drugs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of HIV-1 infected CD4+ T-cells measured by a quantitative HIV-1 DNA PCR assay	96 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
CD4+ T-cells	96 weeks
Plasma HIV-1 RNA	96 weeks
Grade 3 and 4 signs and symptoms or laboratory toxicities at least one grade higher than baseline	From study drug start to 8 weeks after drug discontinuation
Plasma HIV-1 RNA	Baseline to Week 8
Tolerability (Discontinuation of raltegravir)	96 weeks

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Ann C. Collier, MD, University of Washington

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): February 1, 2012
• Study Completion (Anticipated): October 1, 2013

Study Registration Dates

• First Submitted: October 24, 2008
• First Submitted That Met QC Criteria: October 27, 2008
• First Posted (Estimate): October 28, 2008

Study Record Updates

• Last Update Posted (Estimate): August 12, 2013
• Last Update Submitted That Met QC Criteria: August 8, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: HIV-1; raltegravir; human immunodeficiency virus; primary HIV infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: 34908-D