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

NCT01480713 | Completed Phase 3

• 2 other identifiers: RIPIM2011-004464-30
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV-1 Infection

Keywords

HIV-1; protease inhibitors; integrase inhibitors; raltegravir; viral replication; treatment intensification; viral pathogenesis; immune activation

Outcome Measures

Primary Outcomes (3)

• Change from week -8 in Integrated viral HIV-1 DNA in A peripheral blood mononuclear cells (PBMCs) at 8 months.

  week -8, -4, Baseline, week 4, 12 and 24

• Change from week -8 in Unintegrated viral HIV-1 DNA in PBMCs at 8 months.

  week -8, -4, Baseline, week 1, 2, 4, 8, 12 and 24

• Change from week -8 in lymphocyte activation markers in PBMCs at 8 months.

  week -8, -4, Baseline, week 4, 8, 12 and 24

Secondary Outcomes (5)

• ultrasensitive HIV-1 viral load

  week -8, -4, Baseline, week 1, 2, 4, 8, 12 and 24

• viral load >50 copies/mL

  week -8, -4, Baseline, week 1, 2, 4, 8, 12 and 24

• HIV-1 RNA below 50 copies/mL.

  week 24 and 48

• Change in the lymphocyte activation markers

  week -8, -4, Baseline, week 1, 2, 4, 8, 12, and 24 and 48.

• Change in the inflammation markers (soluble CD14, IL-6, D-Dimer, vCam, C Reactive Protein)

  week -8, -4, Baseline, week 4, 8, 12, and 24 and 48

Study Arms (1)

Monotherapy with IPs+ Raltegravir 400 mg

EXPERIMENTAL

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); Drug: Isentress® (Raltegravir, 400 every 12 hours)

Interventions

Isentress® (Raltegravir, 400 mg every 12 hours) DRUG

Lopinavir/r 200/50 mg every 12 hours + Raltegravir 400 mg every 12 hours

Also known as: N/H

Monotherapy with IPs+ Raltegravir 400 mg

Isentress® (Raltegravir, 400 every 12 hours) DRUG

Darunavir/rit 800/100 mg every 24 hours + Raltegravir 400 mg every 12 hours

Also known as: N/H

Monotherapy with IPs+ Raltegravir 400 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• IrsiCaixa: lead

Study Sites (1)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

Related Publications (1)

• Puertas MC, Gomez-Mora E, Santos JR, Molto J, Urrea V, Moron-Lopez S, Hernandez-Rodriguez A, Marfil S, Martinez-Bonet M, Matas L, Munoz-Fernandez MA, Clotet B, Blanco J, Martinez-Picado J. Impact of intensification with raltegravir on HIV-1-infected individuals receiving monotherapy with boosted PIs. J Antimicrob Chemother. 2018 Jul 1;73(7):1940-1948. doi: 10.1093/jac/dky106.

  PMID: 29635527 DERIVED

MeSH Terms

Interventions

Raltegravir Potassium

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2011
• First Posted: November 29, 2011
• Study Start: May 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: May 7, 2024

Record last verified: 2024-04

Locations

ES (1)