Clinical trial NCT00611039: Evaluate the Efficacy and Security of Darunavir/Ritonavir 900/100 mg Once a Day as an Antiretroviral Treatment Simplification Strategy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Darunavir/ritonavir
virtual inhibitory quotient
dose reduction
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2008-02-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: Inclusion Criteria:

1. Age \>= 18 years.
2. HIV-infected patients.
3. Stable antiretroviral treatment including darunavir/ritonavir 600/100 every 12 hours for at least 4 weeks.
4. HIV viral load \< 50 copies/mL for at least 12 weeks.
5. Resistance test (Genotype or Virtual Phenotype) before starting tipranavir treatment.
6. Darunavir vIQ \>= 2.
7. Subject able to follow the treatment period.
8. 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.
9. Signature of the informed consent.

Exclusion Criteria:

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

Primary outcomes:
measure: Proportion of patients with HIV-1 viral load < 50 copies /mL
timeFrame: Basal, week 2, week 4, week 8, week 12 ,week 24week 36 and week 48
Secondary outcomes:
measure: DRV plasma trough concentration
timeFrame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
measure: DRV Virtual inhibitory quotient (vIQ)
timeFrame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
measure: CD4 and CD8 lymphocytes count
timeFrame: Screening, Basal, week 12, week 24, week 36 and week 48
measure: Physical examination including weight and height
timeFrame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
measure: Karnofsky index
timeFrame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week, 36 and week 48
measure: Adverse events
timeFrame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
measure: Lipid profile (total cholesterol, HDL-cholesterol. LDL-cholesterol and triglycerides)
timeFrame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
measure: Treatment adherence (assessed by the physician, but not recovered in the data base)
timeFrame: Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48
measure: Genotype, if virological failure occurs
timeFrame: When virological failure
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
Study officials:
affiliation: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
name: Bonaventura Clotet, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Molto J, Valle M, Santos JR, Mothe B, Miranda C, Cedeno 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. doi: 10.3851/IMP1519.