Integrase Inhibitor (MK-0518) Viral Decay

Study Description

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Brief Summary:

The eradication of HIV by antiretroviral therapy has thus far been elusive. It has been consistently demonstrated that a pool of latently infected, resting CD4+ T cells persists in the majority of HIV-infected individuals receiving antiretroviral therapy in whom plasma viremia has been successfully suppressed for prolonged periods of time; this pool has emerged as the major obstacle in achieving the eradication of HIV. We believe that MK-0518 can further the decay and suppression of HIV-1 in patients who have been virologically suppressed for a prolonged period of time on effective cART (≥ 4 years).

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Raltegravir (MK0518); Drug: Placebo; Procedure: Leukopheresis; Procedure: Sigmoid Biopsy	Phase 2

Detailed Description:

The trial is a prospective, double-blind, randomized, placebo-controlled study with two phases: phase I to 48 weeks and phase II to 96 weeks with the primary analysis at 48 weeks. HIV-infected individuals who are taking their first standard cART regimen for at least four years with complete viral suppression. Upon enrollment, he/she will be randomized to one of two arms: the MK-0518 arm or the control arm. As each participant reaches week 48, he/she will be unblinded and those in the MK-0518 arm will continue taking MK-0518. Based on the results of an interim analysis, the control arm will be rolled over to receive MK-0518 for 48 weeks. After the screening, baseline visits and week 4 safety visit, follow-up visits will occur every 8 weeks for both arms.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	24 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Effect of Integrase Inhibitor (MK-0518) on Decay of Low Level Viral Replication in HIV Reservoirs in Infected Individuals Who Initiated Conventional Antiretroviral Therapy During the Chronic Phase of Infection
Study Start Date :	April 2007
Actual Primary Completion Date :	February 2009
Actual Study Completion Date :	November 2011

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: MK0518 + cART; Raltegravir + standard of care combined antiretroviral therapy	Drug: Raltegravir (MK0518); 400mg BID; 48 weeks Procedure: Leukopheresis; pack of cells as per protocol Procedure: Sigmoid Biopsy; gut samples as per protocol
Placebo Comparator: Placebo + cART; Placebo + standard of care combined antiretroviral therapy	Drug: Placebo; 400mg QD Procedure: Leukopheresis; pack of cells as per protocol Procedure: Sigmoid Biopsy; gut samples as per protocol

Outcome Measures

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Primary Outcome Measures :

1. change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48 [ Time Frame: 48 weeks ]
   evaluate the change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48 in participants randomized to the raltegravir arm (400mg raltegravir) for 48 weeks in addition to their current standard combination antiretroviral regimen versus the control arm, who remained on their current standard combination antiretroviral regimen.

Secondary Outcome Measures :

1. evaluated the effect of raltegravir intensification on blood CD4+ T cell populations [ Time Frame: 48 & 96 weeks ]
   evaluated the effect of raltegravir intensification on blood CD4+ T cell populations. In addition, after treatment-intensification in both groups at week 48, a post-hoc follow-up of all participants was conducted up to week 96 to examine if raltegravir intensification had any long-term effects on proviral HIV DNA and CD4+ T cell populations in the blood and gut.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Participant must be HIV-1 infected
2. Participant must be 18 years old
3. Participant must be taking first standard cART with 2-3 NRTIs and 1-2 PIs or an NNRTI for at least four years (first cART regimen may include changes due to toxicity but not due to virologic failure).
4. Participant must have a VL < 50 copies/ml (using the standard available methods of detection) during the entire time on standard cART except for initial fall of VL and a maximum of two non-consecutive blips of < 100 copies/ml that the study investigator deems to be not clinically significant
5. Female participant must agree to use two methods of birth control or abstinence during the period of the study
6. Participant has to have signed full informed consent

Exclusion Criteria:

1. Participant who would have difficulty participating in a trial due to non-adherence or substance abuse
2. Participant who has taken mono or dual antiretroviral therapy in the past
3. Participant who has had a VL > 50 copies/ml on any antiretroviral regimen

4. Participant with any of the following abnormal laboratory test results in screening:

   • Hemoglobin < 100 g/L
   • Neutrophil count < 750 cells/L
   • Platelet count < 50,000 cells/L
   • AST or ALT > 5X the upper limit of normal
   • Creatinine > 250 mol/L
5. Participant with a malignancy
6. Participant with other significant underlying disease (non-HIV) that might impinge upon disease progression or death
7. Participant with an active AIDS-defining illness in the past six months
8. Participant who is pregnant

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Canada, Ontario
Maple Leaf Medical Clinic
Toronto, Ontario, Canada, M5B 1L6

Sponsors and Collaborators

Canadian Immunodeficiency Research Collaborative

National Institutes of Health (NIH)

Investigators

Principal Investigator:	Mona Loutfy, MD	Women's College Hospital

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Canadian Immunodeficiency Research Collaborative
ClinicalTrials.gov Identifier:	NCT00520897 History of Changes
Other Study ID Numbers:	038-00
First Posted:	August 27, 2007
Last Update Posted:	June 5, 2012
Last Verified:	June 2012

Keywords provided by Canadian Immunodeficiency Research Collaborative:

chronic HIV infection; Human Immunodeficiency Virus; Treatment Experienced

Additional relevant MeSH terms:

Infection; HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases	Raltegravir Potassium; Integrase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; HIV Integrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action