Darunavir Levels, Virological Efficacy, Proviral ADN and Resistances in Patients on Darunavir/Ritonavir Monotherapy (MonDar)

Relation Between Darunavir Levels and Virological Efficacy, Integrated Proviral ADN and Resistance Mutations in HIV-infected Patients on Treatment With Darunavir/Ritonavir Monotherapy

To evaluate the relationship between plasma and intracellular darunavir (DRV) concentrations and virological efficacy in HIV-infected patients on DRV/rtv monotherapy.

Study Overview

• Status: Completed
• Conditions: HIV-infection
• Intervention / Treatment: Drug: Darunavir/ritonavir

Detailed Description

To be enrolled, subjects had a plasma HIV-RNA <50 copies/mL for at least 6 months based, virologic failure while on a PI-containing regimen was allowed if the genotypic resistance tests showed no major resistance mutation associated to reduced susceptibility to DRV/rtv according to the International AIDS Society. Patients with transitory episodes of detectable plasma HIV-RNA viral load ("blip") preceded and followed by a plasma viral load <50 copies/mL without changes in antiretroviral treatment could also been included. The only exclusion criteria were pregnancy, hepatitis B coinfection and the concomitant use of drugs with potential major interactions with DRV/rtv pharmacokinetics.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• Spain
  • Seville, Spain, 41013
    • Hospital Universitarios Virgen del Rocio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-infected patients who started an antiretroviral regimen based on darunavir-ritonavir (800/100 mg) once daily monotherapy between June 2010 and September 2010

Description

Inclusion Criteria:

• Older than 18 years, starting an antiretroviral regimen based on darunavir-ritonavir (800/100 mg) once daily monotherapy between June 2010 and September 2010
• Plasma RNA-VIH < 50 copies/ml on stable antiretroviral treatment for ≥ 6 months
• Absence of resistance mutations in the protease gene, based on treatment history and/or genotypic resistance testing. that would decrease darunavir susceptibility

Exclusion Criteria:

• Pregnancy
• Chronic B hepatitis
• Genotypic resistance tests with evidence of resistance mutations in the protease gene that would decrease darunavir susceptibility
• Concomitant use of drugs with potentially adverse interactions with darunavir-ritonavir pharmacokinetics, such as rifampin

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Darunavir-ritonavir monotherapy; HIV-infected patients with undetectable viral load for at least for 6 months on stable therapy and no darunavir related mutations in the HIV-protease gene	Drug: Darunavir/ritonavir; Darunavir/ritonavir (800/100 mg once daily) monotherapy; Other Names: Prezista/norvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological efficacy	To correlate the plasma and intracellular (cell-associated)) DRV levels with the virological efficacy analyzed by the time to loss of virological response (TLOVR) algorithm, considering VF as either: 1) two consecutive viral load >200 copies/mL, 2) a unique HIV-RNA >200 copies/mL if followed by lost to follow-up, or 3) the reintroduction of nucleos(t)ides because any reason.	48 and 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of viral breakthrough on DNA-HIV reservoirs and immunologic activation	Impact of blips and persistent viraemia on DNA-HIV reservoirs and immunologic activation	48 and 96 weeks

Collaborators and Investigators

• Sponsor: Hospitales Universitarios Virgen del Rocío
• Investigators: Study Chair: Luis F Lopez-Cortes, MD, PhD., Hospital Universitario Virgen del Rocio. Sevilla. Spain

Publications and helpful links

General Publications

• Gutierrez-Valencia A, Torres-Cornejo A, BenMarzouk-Hidalgo OJ, Ruiz-Valderas R, Lluch A, Viciana P, Lopez-Cortes LF. Darunavir minimum plasma concentration and ritonavir-boosted darunavir monotherapy outcome in HIV-infected patients. Antivir Ther. 2014;19(5):443-7. doi: 10.3851/IMP2722. Epub 2014 Jan 16.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: May 24, 2012
• First Submitted That Met QC Criteria: May 25, 2012
• First Posted (Estimate): May 28, 2012

Study Record Updates

• Last Update Posted (Estimate): July 11, 2013
• Last Update Submitted That Met QC Criteria: July 10, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Resistance; Antiretroviral therapy; Boosted-Darunavir monotherapy; Proviral DNA-HIV
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Darunavir
• Other Study ID Numbers: LLC-DAR-2010-01 (Other Grant/Funding Number: Consejeria de Salud. Junta de Andalucia (exp: PI-0448-2010))