Clinical trial NCT00935480: IntensVIH: Impact Of Therapy Intensification By An Integrase Inhibitor +/- CCR5 Inhibitor On The Lymphoid Reservoir For Hiv-1 In Chronically Infected Patients
Official title: IMPACT OF THERAPY INTENSIFICATION BY AN INTEGRASE INHIBITOR +/- CCR5 INHIBITOR ON THE LYMPHOID RESERVOIR FOR HIV-1 IN CHRONICALLY INFECTED PATIENTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV
INTEGRASE INHIBITOR
Inhibitor on the lymphoid reservoir
Residual HIV replication
treatment experienced
Lead sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Abbott
First posted: 2009-07-09
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: residual plasma replication between 0 and 50 copies/ml
timeFrame: one year
measure: intracellular HIV RNA levels in circulating lymphocytes (PBMC) and lymphocytes in gut-associated rectal lymphoid tissue (RL
timeFrame: one year
measure: proviral HIV DNA levels in PBMC and RL
timeFrame: one year
Secondary outcomes:
measure: CD4 counts
timeFrame: one year
measure: CD8 activation levels
timeFrame: one year
Other outcomes:
Locations:
city: Toulon
country: France
facility: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer, Service d'infectiologie
city: Toulon
country: France
facility: Centre Hospitalier Intercommunal de Toulon La Seyne sur mer
Study officials:
References:
citation: 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.