Evaluate the Efficacy and Security of Darunavir/Ritonavir 900/100 mg Once a Day as an Antiretroviral Treatment Simplification Strategy (DRV900100QD)

• 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 ]

• DRV plasma trough concentration [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12 and week 24 ] [ Designated as safety issue: Yes ]
• DRV Virtual inhibitory quotient (vIQ) [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12 and week 24 ] [ Designated as safety issue: Yes ]
• CD4 and CD8 lymphocytes count [ Time Frame: Screening, Basal, week 12 and week 24 ] [ Designated as safety issue: No ]
• Physical examination including weight and height [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12 and week 24 ] [ Designated as safety issue: Yes ]
• Karnofsky index [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12 and week 24 ] [ Designated as safety issue: Yes ]
• Adverse events [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12 and week 24 ] [ 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 and week 24 ] [ Designated as safety issue: Yes ]
• Treatment adherence (assesed by the phisician, but not recovered in the data base) [ Time Frame: Screening, Basal, week 2, week 4, week 8, week 12 and week 24 ] [ Designated as safety issue: Yes ]
• Genotype, if virological failure occurs [ Time Frame: When virological failure ] [ Designated as safety issue: No ]

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.

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.

• Drug: Darunavir 900mg + ritonavir 100 mg once a day
  Darunavir 900mg + ritonavir 100 mg once a day
• Drug: Darunavir 600mg + ritonavir 100mg twice day
  Darunavir 600mg + ritonavir 100mg twice day

• Experimental: 1
  Darunavir 900mg + ritonavir 100 mg once a day
  Intervention: Drug: Darunavir 900mg + ritonavir 100 mg once a day
• Active Comparator: 2
  Darunavir 600mg + ritonavir 100mg twice day
  Intervention: Drug: Darunavir 600mg + ritonavir 100mg twice day

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.