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

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Abbott
Information provided by (Responsible Party):
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
ClinicalTrials.gov Identifier:
NCT00935480
First received: July 8, 2009
Last updated: April 16, 2014
Last verified: April 2014
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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 ]

Enrollment: 17
Study Start Date: July 2010
Study Completion Date: February 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HAART+Raltegravir 12 months (+/-) Maraviroc 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)
No Intervention: HAART

  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:

  1. Opportunistic infection or active tumor disease
  2. Chronic diarrhea, malabsorption, progressive enteric infection
  3. Aged under 18 years
  4. Pregnancy - breast-feeding ( a pregnancy test will be done at the inclusion visit)
  5. Co-infection with HIV-2
  6. History of immunomodulator treatment (interleukin-2, alpha-interferon)
  7. Ongoing treatment of HBV or HCV co-infection
  8. Blood constitution disorders
  9. Contraindications to the administration of raltegravir or maraviroc
  10. Circulating CD4 nadir <100/mm3 in the natural history of HIV-1 infection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
France
Centre Hospitalier Intercommunal de Toulon La Seyne sur mer
Toulon, France, 83500
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer, Service d'infectiologie
Toulon, France, 83056
Sponsors and Collaborators
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Merck Sharp & Dohme Corp.
Abbott
  More Information

No publications provided

Responsible Party: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
ClinicalTrials.gov Identifier: NCT00935480     History of Changes
Other Study ID Numbers: CH-2009.01
Study First Received: July 8, 2009
Last Updated: April 16, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014