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

Phase 3

Completed

• Conditions: HIV Infections
• Interventions: Drug: Isentress®; Drug: Celsentri®

• Registration Number: NCT00935480
• Lead Sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-07-08
• Study First Submitted QC: 2009-07-08
• Study First Posted: 2009-07-09
• Study Start: 2010-10
• Primary Completion: 2010-11-12
• Study Completion: 2014-08-08
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-11
• Last Update Posted: 2017-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HAART+Raltegravir 12 months (+/-) Maraviroc	Isentress®	-
HAART+Raltegravir 12 months (+/-) Maraviroc	Celsentri®	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
CD4 counts	one year
CD8 activation levels	one year

Trial Locations

Locations (2)

Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer, Service d'infectiologie; 🇫🇷 Toulon, France

Centre Hospitalier Intercommunal de Toulon La Seyne sur mer; 🇫🇷 Toulon, France