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

HIV Infections Clinical Trial

— IntensVIH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00935480
• Other study ID #: CH-2009.01
• Status: Completed
• Phase: Phase 3
• First received: July 8, 2009
• Last updated: May 11, 2017
• Start date: October 2010
• Est. completion date: August 8, 2014

Study information

• Verified date: May 2017
• Source: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: August 8, 2014
• Est. primary completion date: November 12, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Isentress®
P.O, 1 tablet containing 400 mg every 12 hours
• Celsentri®
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)

Locations

Country	Name	City	State
France	Centre Hospitalier Intercommunal de Toulon La Seyne sur mer	Toulon
France	Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer, Service d'infectiologie	Toulon

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer	Abbott, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	residual plasma replication between 0 and 50 copies/ml		one year
Primary	intracellular HIV RNA levels in circulating lymphocytes (PBMC) and lymphocytes in gut-associated rectal lymphoid tissue (RL		one year
Primary	proviral HIV DNA levels in PBMC and RL		one year
Secondary	CD4 counts		one year
Secondary	CD8 activation levels		one year