A Study to Compare Effectiveness and Safety of Darunavir/Ritonavir (DRV/Rtv) 800mg/100mg Once Daily Versus DRV/Rtv 600mg/100mg Twice Daily in Early Treatment-Experienced HIV-1 Infected Patients (ODIN)

• Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
  
  

• Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  Number of participants with confirmed plasma viral load less than 400 copies/mL at Week 48.
  
  
• Change in log10 Viral Load From Baseline at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  
• Time to Reach First Virologic Response [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  Time (in weeks) to achieve viral load less than 50 copies/mL by the participants.
  
  
• Time to Loss of Virologic Response [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  Time taken to lose the virologic response ie, plasma viral load less than 50 copies/mL by participants.
  
  
• Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  
• Change in CD4+ Cell Count From Baseline [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  CD4+ cell count was calculated using the Last Observation Carried Forward (LOCF) algorithm.
  
  
• Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  The FAHI is a 44-item questionnaire and incorporates 5 functional scales (physical well-being, emotional well-being/living with HIV, functional and global well-being, social well-being, and cognitive functioning). Each scale included several questions (all 5 scales include total 44 questions). For each question, participants gave a score of either 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). Total FAHI imputed score is calculated by adding scores for each question. The range of total FAHI score is 0 to 176. Higher scores indicate worsening.
  
  
• Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  Self-reported adherence to the ARV medications was measured. The M-MASRI asks participants to report the number of doses taken, as well as the number of doses taken during the last 30 days prior to the study visit by means of a horizontal visual analogue scale (VAS) that generates a self-rated percentage of doses of all the ARV medications taken during the past 30 days.
  
  
• Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv [ Time Frame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48. ] [ Designated as safety issue: No ]
  Pharmacokinetic parameter AUC24h was assessed from the time of study medication administration upto 24 hour postdose. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.
  
  
• Predose Plasma Concentration (C0h) of DRV and Rtv. [ Time Frame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48 ] [ Designated as safety issue: No ]
  Pharmacokinetic parameter C0h was assessed. Population Pharmacokinetic Estimates of DRV and rtv were evaluated.
  
  
• Number of Participants Developing Mutations at Endpoint [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  Development of Mutations in Virologic Failures (Plasma Viral Load less than 50 Copies/mL) at endpoint.
  
  

This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention) study in which 590 patients will be randomly assigned to receive either DRV/rtv 800/100 mg daily or DRV/rtv 600/100 mg twice daily along with the selected OBR. An OBR will consist of at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) selected by the investigator. The study will include a 4 week screening period, 48-weeks of treatment period and 4-weeks of follow-up. The study will also consists of extension phase after Week 48: in regions where DRV is not yet commercially available or reimbursed by the health care system, patients who complete the 48 weeks of treatment with DRV/rtv and who continue to benefit from this treatment, will have the opportunity to continue DRV treatment as a 600 mg twice daily dosage until DRV is reimbursed and available via the public and/or private health care system or until its development is discontinued. Safety evaluation will consists of adverse events (including specific toxicities), clinical laboratory tests, vital signs, electrocardiogram, physical and skin examination.