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

Study Overview
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Brief Summary
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Isentress®
* Drug: Celsentri®


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAART+Raltegravir 12 months (+/-) Maraviroc<br> | Drug: Isentress®<br>* P.O, 1 tablet containing 400 mg every 12 hours<br>Drug: Celsentri®<br>* 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)<br>|
| No Intervention: HAART<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 counts |  | one year | 
| CD8 activation levels |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, INTEGRASE INHIBITOR, Inhibitor on the lymphoid reservoir, Residual HIV replication, treatment experienced