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

Study Overview
=================
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.

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

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: Darunavir 900mg + ritonavir 100 mg once a day
* Drug: Darunavir 600mg + ritonavir 100mg twice day


Participation Criteria
=================
Eligibility 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Darunavir 900mg + ritonavir 100 mg once a day | Drug: Darunavir 900mg + ritonavir 100 mg once a day<br>* Darunavir 900mg + ritonavir 100 mg once a day<br>|
| Active Comparator: 2<br>Darunavir 600mg + ritonavir 100mg twice day | Drug: Darunavir 600mg + ritonavir 100mg twice day<br>* Darunavir 600mg + ritonavir 100mg twice day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with HIV-1 viral load < 50 copies /mL |  | Basal, week 2, week 4, week 8, week 12 ,week 24week 36 and week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DRV plasma trough concentration |  | Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| DRV Virtual inhibitory quotient (vIQ) |  | Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| CD4 and CD8 lymphocytes count |  | Screening, Basal, week 12, week 24, week 36 and week 48 | 
| Physical examination including weight and height |  | Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| Karnofsky index |  | Screening, Basal, week 2, week 4, week 8, week 12, week 24, week, 36 and week 48 | 
| Adverse events |  | Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| Lipid profile (total cholesterol, HDL-cholesterol. LDL-cholesterol and triglycerides) |  | Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| Treatment adherence (assessed by the physician, but not recovered in the data base) |  | Screening, Basal, week 2, week 4, week 8, week 12, week 24, week 36 and week 48 | 
| Genotype, if virological failure occurs |  | When virological failure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Darunavir/ritonavir, virtual inhibitory quotient, dose reduction