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

• Status: Completed
• Trial end date: 2014-08-08
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Collaborators: Abbott; Merck Sharp & Dohme Corp.
• Treatments: Integrase Inhibitors; Raltegravir Potassium

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.