Evaluate the Efficacy and Security of Darunavir/Ritonavir 900/100 mg Once a Day as an Antiretroviral Treatment Simplification Strategy - Full Text View

Sponsor:	Germans Trias i Pujol Hospital
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00611039

Purpose

Basing in studies which have related the darunavir (DRV) virtual inhibitory quotient (vIQ) with the virological response, it is possible to think in the possibility of simplifying the rescue treatment with DRV/ritonavir to 900/100 mg once a day in those patients who are being treated with DRV/ritonavir 600/100 mg twice a day and who, besides having undetectable viral load, have a vIQ over 2. This strategy would not jeopardize the efficacy of the antiretroviral treatment and would have less impact in the lipid profile of the patients as well as less pharmaceutical expenditure.

Condition	Intervention	Phase
HIV Infections	Drug: Darunavir 900mg + ritonavir 100 mg once a day Drug: Darunavir 600mg + ritonavir 100mg twice day	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Clinical Pilot, Open, Comparative and Randomized Trial to Evaluate the Efficacy and Security of Darunavir/Ritonavir 900/100 mg Once a Day as an Antiretroviral Treatment Simplification Strategy

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Darunavir Darunavir ethanolate

U.S. FDA Resources

Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:

Proportion of patients with HIV-1 viral load < 50 copies /mL [ Time Frame: Basal, week 2, week 4, week 8, week 12 ,week 24week 36 and week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

DRV plasma trough concentration [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: Yes ]
DRV Virtual inhibitory quotient (vIQ) [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: Yes ]
CD4 and CD8 lymphocytes count [ Time Frame: Screening, Basal, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: No ]
Physical examination including weight and height [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: Yes ]
Karnofsky index [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week, 36 and week 48 ] [ Designated as safety issue: Yes ]
Adverse events [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: Yes ]
Lipid profile (total cholesterol, HDL-cholesterol. LDL-cholesterol and triglycerides) [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: Yes ]
Treatment adherence (assessed by the physician, but not recovered in the data base) [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 ] [ Designated as safety issue: Yes ]
Genotype, if virological failure occurs [ Time Frame: When virological failure ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	February 2008
Study Completion Date:	July 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Darunavir 900mg + ritonavir 100 mg once a day	Drug: Darunavir 900mg + ritonavir 100 mg once a day Darunavir 900mg + ritonavir 100 mg once a day
Active Comparator: 2 Darunavir 600mg + ritonavir 100mg twice day	Drug: Darunavir 600mg + ritonavir 100mg twice day Darunavir 600mg + ritonavir 100mg twice day

Detailed Description:

The probability of achieving viral replication suppression during the treatment with DRV has been related to both the extent of viral resistance to DRV (inhibitory concentration 50%, IC50) and the drug concentration. Moreover, the DRV virtual inhibitory quotient (vIQ) has been related significantly with the virological response to DRV treatment. So patients with a DRV vIQ >= 1,5 had a 8-times higher probability of having viral load < 50 copies/mL after 24 weeks of treatment than those having a vIQ < 1,5.

Considering the previous arguments, it is possible to think in the possibility of simplifying the rescue treatment with DRV/ritonavir to 900/100 mg once a day in those patients who are being treated with DRV/ritonavir 600/100 mg twice a day and who, besides having undetectable viral load, have a DRV vIQ over 2. This strategy would not jeopardize the efficacy of the antiretroviral treatment and would have less impact in the lipid profile of the patients as well as less pharmaceutical expenditure.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age >= 18 years.
HIV-infected patients.
Stable antiretroviral treatment including darunavir/ritonavir 600/100 every 12 hours for at least 4 weeks.
HIV viral load < 50 copies/mL for at least 12 weeks.
Resistance test (Genotype or Virtual Phenotype) before starting tipranavir treatment.
Darunavir vIQ >= 2.
Subject able to follow the treatment period.
In women, negative pregnancy test or not in fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or undertaking to use a barrier contraceptive method during the study.
Signature of the informed consent.

Exclusion Criteria:

AIDS-defining illness in the last 4 weeks.
Suspicion of unsuitable antiretroviral treatment compliance.
In women, pregnancy or breastfeeding.
Record or suspicion of incapability to cooperate as appropriate.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00611039

Locations

Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916

Sponsors and Collaborators

Germans Trias i Pujol Hospital

Investigators

Principal Investigator:

Bonaventura Clotet, MD,PhD

Fundacio Lluita Contra la SIDA

More Information

No publications provided by Germans Trias i Pujol Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Moltó J, Valle M, Santos JR, Mothe B, Miranda C, Cedeño S, Negredo E, Yritia M, Videla S, Barbanoj MJ, Clotet B. Treatment simplification to once daily darunavir/ritonavir guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients. Antivir Ther. 2010;15(2):219-25.

Responsible Party:	LLuita Sida Foundation
ClinicalTrials.gov Identifier:	NCT00611039 History of Changes
Other Study ID Numbers:	DRV 900100 QD
Study First Received:	January 28, 2008
Last Updated:	October 5, 2009
Health Authority:	Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:

Darunavir/ritonavir
virtual inhibitory quotient
dose reduction

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir

Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012