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

Intermunicipal Hospital Center Toulon

Status and phase: Completed; Phase 3

Conditions: HIV Infections

Treatments: Drug: Celsentri®; Drug: Isentress®

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00935480

CH-2009.01

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 2 patient groups

HAART+Raltegravir 12 months (+/-) Maraviroc

Experimental group

Treatment:

Drug: Celsentri®

Drug: Isentress®

HAART

No Intervention group