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

NCT00935480 | Completed Phase 3

• 1 other identifier: CH-2009.01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

HIV Infections

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• CD4 counts

  one year

• CD8 activation levels

  one year

Study Arms (2)

HAART+Raltegravir 12 months (+/-) Maraviroc

EXPERIMENTAL

Drug: Isentress®; Drug: Celsentri®

HAART

NO INTERVENTION

Interventions

Isentress® DRUG

P.O, 1 tablet containing 400 mg every 12 hours

HAART+Raltegravir 12 months (+/-) Maraviroc

Celsentri® DRUG

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)

HAART+Raltegravir 12 months (+/-) Maraviroc

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• Opportunistic infection or active tumor disease
• Chronic diarrhea, malabsorption, progressive enteric infection
• Aged under 18 years
• 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.

Sponsors & Collaborators

• Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer: lead
• Merck Sharp & Dohme LLC: collaborator
• Abbott: collaborator

Study Sites (2)

Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer, Service d'infectiologie

Toulon, 83056, France

Location

Centre Hospitalier Intercommunal de Toulon La Seyne sur mer

Toulon, 83500, France

Location

Related Publications (1)

• 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.

  PMID: 25320633 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; Maraviroc

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2009
• First Posted: July 9, 2009
• Study Start: October 1, 2010
• Primary Completion: November 12, 2010
• Study Completion: August 8, 2014
• Last Updated: May 12, 2017

Record last verified: 2017-05

Locations

FR (2)