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

IMPACT OF THERAPY INTENSIFICATION BY AN INTEGRASE INHIBITOR +/- CCR5 INHIBITOR ON THE LYMPHOID RESERVOIR FOR HIV-1 IN CHRONICALLY INFECTED PATIENTS

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Isentress®; Drug: Celsentri®

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Toulon, France, 83056
    • Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer, Service d'infectiologie
  • Toulon, France, 83500
    • Centre Hospitalier intercommunal de Toulon La Seyne sur Mer

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:

• 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.

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: 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
CD4 counts	one year
CD8 activation levels	one year

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Collaborators: Merck Sharp & Dohme LLC; Abbott

Publications and helpful links

General Publications

• Lafeuillade A, Assi A, Poggi C, Bresson-Cuquemelle C, Jullian E, Tamalet C. Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial. AIDS Res Ther. 2014 Oct 7;11(1):33. doi: 10.1186/1742-6405-11-33. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): November 12, 2010
• Study Completion (Actual): August 8, 2014

Study Registration Dates

• First Submitted: July 8, 2009
• First Submitted That Met QC Criteria: July 8, 2009
• First Posted (Estimate): July 9, 2009

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 11, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: HIV; treatment experienced; INTEGRASE INHIBITOR; Inhibitor on the lymphoid reservoir; Residual HIV replication
• 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; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; 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: CH-2009.01