IntensVIH: Impact Of Therapy Intensification By An Integrase Inhibitor +/- CCR5 Inhibitor On The Lymphoid Reservoir For Hiv-1 In Chronically Infected Patients

This study is not yet open for participant recruitment.

Verified by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer, July 2009

First Received: July 8, 2009 Last Updated: August 6, 2009 History of Changes

Sponsor:	Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Collaborators:	Merck Abbott
Information provided by:	Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
ClinicalTrials.gov Identifier:	NCT00935480

Purpose

To determine the efficacy of adding Isentress®, with or without Celsentri®, to effective conventional antiretroviral therapy (comprising at least 2 reverse transcriptase inhibitors and one boosted protease inhibitor), on residual HIV replication and blood cell and gut-associated lymphoid tissue reservoirs (reverse transcriptase inhibitors: RTIs, boosted protease inhibitors: PI/r).

To evaluate the effect of therapy intensification by means of an integrase inhibitor with or without CCR5 inhibitor treatment on the lymphoid reservoir in patients chronically infected with HIV-1, successfully treated with "conventional triple therapy", measured by:

residual plasma replication between 0 and 50 copies/ml
intracellular HIV RNA levels in circulating lymphocytes (PBMC) and lymphocytes in gut-associated rectal lymphoid tissue (RL).
proviral HIV DNA levels in PBMC and RL.

Condition	Intervention	Phase
HIV Infections	Drug: Isentress® Drug: Celsentri®	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	IMPACT OF THERAPY INTENSIFICATION BY AN INTEGRASE INHIBITOR +/- CCR5 INHIBITOR ON THE LYMPHOID RESERVOIR FOR HIV-1 IN CHRONICALLY INFECTED PATIENTS

Resource links provided by NLM:

MedlinePlus related topics: AIDS

U.S. FDA Resources

Further study details as provided by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer:

Primary Outcome Measures:

residual plasma replication between 0 and 50 copies/ml [ Time Frame: one year ] [ Designated as safety issue: No ]
intracellular HIV RNA levels in circulating lymphocytes (PBMC) and lymphocytes in gut-associated rectal lymphoid tissue (RL [ Time Frame: one year ] [ Designated as safety issue: No ]
proviral HIV DNA levels in PBMC and RL [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

CD4 counts [ Time Frame: one year ] [ Designated as safety issue: No ]
CD8 activation levels [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment:	35
Study Start Date:	October 2009
Estimated Study Completion Date:	October 2011
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
HAART+Raltegravir 12 months: Experimental	Drug: Isentress® P.O, 1 tablet containing 400 mg every 12 hours
HAART+Raltegravir 6 months: Experimental delayed intensification	Drug: Isentress® P.O, 1 tablet containing 400 mg every 12 hours
HAART+Raltegravir+Maraviroc 6 months: Experimental Delayed intensification	Drug: Isentress® P.O, 1 tablet containing 400 mg every 12 hours Drug: Celsentri® p.o.: 1 tablet containing 150 mg morning and evening (due to combination with PI/r) or containing 300 mg if fosamprenavir/r is used as the PI (MA)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female patients, aged over 18 years
HIV infection confirmed by Western Blot
Karnofsky score > 80%
Treatment-experienced patients having received combined antiretroviral therapy including at least 2 RTI and 1 PI/r for at least 12 months with plasma viral load <50 copies/ml for at least 6 months
Stable first-line treatment (or other, if changes were not made for reasons relating to viral resistance) with 2 RTIs and 1 PI/r
Proper safety and compliance for the ongoing combination;
Patient agreeing to undergo 3 proctosigmoidoscopy examinations over a 12-month period;
Plasma HIV-1 RNA <50 copies/ml at inclusion;
Circulating CD4 >200/mm3 at inclusion;
Isentress® and Celsentri®-naïve patients
No contraindications to the use of the investigational products
Written, informed consent, obtained from the patient or his/her legal representative.

Exclusion Criteria:

Opportunistic infection or active tumor disease
Chronic diarrhea, malabsorption, progressive enteric infection
Aged under 18 years
Pregnancy - breast-feeding ( a pregnancy test will be done at the inclusion visit)
Co-infection with HIV-2
History of immunomodulator treatment (interleukin-2, alpha-interferon)
Ongoing treatment of HBV or HCV co-infection
Blood constitution disorders
Contraindications to the administration of raltegravir or maraviroc
Circulating CD4 nadir <100/mm3 in the natural history of HIV-1 infection.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00935480

Contacts

Contact: Alain Lafeuillade, Dr

33 494 618 023

alain.lafeuillade@ch-toulon.fr

Locations

France
Centre Hospitalier Intercommunal de Toulon La Seyne sur mer
Toulon, France, 83500

Sponsors and Collaborators

Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

Merck

Abbott

More Information

No publications provided

Responsible Party:	Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer ( Dr LAFEUILLADE Alain )
Study ID Numbers:	CH-2009.01
Study First Received:	July 8, 2009
Last Updated:	August 6, 2009
ClinicalTrials.gov Identifier:	NCT00935480 History of Changes
Health Authority:	France: Afssaps - French Health Products Safety Agency

Keywords provided by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer:

HIV
INTEGRASE INHIBITOR
Inhibitor on the lymphoid reservoir
Residual HIV replication
treatment experienced

Additional relevant MeSH terms:

RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection

Pharmacologic Actions
Immunologic Deficiency Syndromes
Virus Diseases
HIV Infections
Integrase Inhibitors
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010