Impact of Raltegravir Intensification on HIV-1-infected Subjects With Complete Viral Suppression Under Monotherapy With Protease Inhibitors - Full Text View

Purpose

This is a pilot, proof of concept, open-label clinical trial, to assess the extend of persistent viral reservoir and the level of immune activation in patients receiving suppressive treatment with protease inhibitors.

40 Chronically HIV-1 infected subjects, receiving monotherapy with ritonavir-boosted lopinavir or darunavir for at least 12 months with plasma viremia below 50 copies HIV RNA per ml, and CD4 T-cell counts greater than 500 cells/mm3 will be included.

The total duration of the study will be 48 weeks: 12 weeks for patients' inclusion, 24 weeks of follow-up once the last patient is included, and 12 weeks for data analysis.

Condition	Intervention	Phase
HIV-1 Infection	Drug: Isentress® (Raltegravir, 400 mg every 12 hours) Drug: Isentress® (Raltegravir, 400 every 12 hours)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Impact of Raltegravir Intensification on HIV-1-infected Subjects With Complete Viral Suppression Under Monotherapy With Protease Inhibitors. A 24-week Open-label, Proof-of-concept Pilot Clinical Trial.

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by IrsiCaixa:

Primary Outcome Measures:

Change from week -8 in Integrated viral HIV-1 DNA in A peripheral blood mononuclear cells (PBMCs) at 8 months. [ Time Frame: week -8, -4, Baseline, week 4, 12 and 24 ] [ Designated as safety issue: No ]
Change from week -8 in Unintegrated viral HIV-1 DNA in PBMCs at 8 months. [ Time Frame: week -8, -4, Baseline, week 1, 2, 4, 8, 12 and 24 ] [ Designated as safety issue: No ]
Change from week -8 in lymphocyte activation markers in PBMCs at 8 months. [ Time Frame: week -8, -4, Baseline, week 4, 8, 12 and 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

ultrasensitive HIV-1 viral load [ Time Frame: week -8, -4, Baseline, week 1, 2, 4, 8, 12 and 24 ] [ Designated as safety issue: No ]
viral load >50 copies/mL [ Time Frame: week -8, -4, Baseline, week 1, 2, 4, 8, 12 and 24 ] [ Designated as safety issue: No ]
HIV-1 RNA below 50 copies/mL. [ Time Frame: week 24 ] [ Designated as safety issue: No ]
Change in the lymphocyte activation markers [ Time Frame: week -8, -4, Baseline, week 1, 2, 4, 8, 12 and 24 ] [ Designated as safety issue: No ]
Change in the inflammation markers (soluble CD14, IL-6, D-Dimer, vCam, C Reactive Protein) [ Time Frame: week -8, -4, Baseline, week 4, 8, 12 and 24 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	May 2012
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Monotherapy with IPs+ Raltegravir 400 mg Lopinavir/r 400/100 mg every 12 hours + Raltegravir 400 mg every 12 hours or Darunavir/rit 800/100 mg every 24 hours + Raltegravir 400 mg every 12 hours	Drug: Isentress® (Raltegravir, 400 mg every 12 hours) Lopinavir/r 200/50 mg every 12 hours + Raltegravir 400 mg every 12 hours Other Name: N/H Drug: Isentress® (Raltegravir, 400 every 12 hours) Darunavir/rit 800/100 mg every 24 hours + Raltegravir 400 mg every 12 hours Other Name: N/H

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 infected adults (≥18 years old).
Absence of prior virological failure with protease inhibitors (PIs).
No mono or dual protease inhibitor therapy previous to HAART initiation.
Patients had to be on monotherapy with ritonavir-boosted lopinavir (LPV/r 400/100 mg every 12 hours) or darunavir (DRV/r 800/100 mg every 24 hours) for ≥ 12 months. Switching from standard HAART to protease inhibitor monotherapy had to happen with undetectable plasma viremia.
Complete virological suppression (<50 copies/mL) for ≥12 months, including at least 2 times during the last year.
CD4 cell count ≥500 cells/µL.
Availability (if possible, not mandatory) of a genotype prior to the start of HAART, with absence of any major drug-related mutations.
Voluntary written informed consent.

Exclusion Criteria:

Lactating, pregnancy, or fertile women willing to be pregnant.
Active substance abuse or major psychiatric disease.
Presence of any polymorphism or mutation associated to raltegravir resistance at baseline (prior to first HAART).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01480713

Locations

Spain
Germans Trias i Pujol Hospital	Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Silvia Gel 0034934978414 sgel@fls-rs.com
Principal Investigator: Javier Martínez-Picado, MD,PhD
Sub-Investigator: Jose Ramón Santos, MD

Sponsors and Collaborators

IrsiCaixa

More Information

No publications provided

Responsible Party:	IrsiCaixa
ClinicalTrials.gov Identifier:	NCT01480713 History of Changes
Other Study ID Numbers:	RIPIM, 2011-004464-30
Study First Received:	November 21, 2011
Last Updated:	August 6, 2012
Health Authority:	Spain: Ministry of Health

Keywords provided by IrsiCaixa:

HIV-1
protease inhibitors
integrase inhibitors
raltegravir

viral replication
treatment intensification
viral pathogenesis
immune activation

Additional relevant MeSH terms:

HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases

Immunologic Deficiency Syndromes
Immune System Diseases
Protease Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013