Efficacy Study of Substitution of Darunavir/Ritonavir (DRV/r) for Dual-boosted Protease Inhibitors

Inclusion Criteria: * Age 18 years or older * Treatment with a stable antiretroviral regimen containing two protease inhibitors, one additional FDA-licensed agent from another class (except NNRTIs) and a boosting dosage of ritonavir (100 BID or QD) for at least 12 weeks prior to screening * No plans to make any changes in HIV treatment regimen (other than those required by study) in the next 48 weeks. * HIV-1 RNA \< 400 copies/ml based on the most recent value done as part of routine care at least 12 weeks prior to screening; and \< 400 at screening * Any CD4 count is allowed * Written informed consent to participate Exclusion Criteria: * Current regimen includes an NNRTI * CDC Class C Illness diagnosed within 30 days of screening * Lab abnormalities as defined by a standardized grading scheme based on the DAIDS table * Any grade 3 or 4 toxicity with the following exceptions: * Pre-existing diabetes with glucose elevations ≥ grade 3 * triglyceride or total cholesterol elevations ≥ grade 3 * Clinical or laboratory evidence of clinically significant liver impairment/dysfunction, disease or cirrhosis Note: Individuals co-infected with chronic hepatitis B or C will be allowed to enter the trial if their condition is clinically stable. Individuals diagnosed with acute viral hepatitis at screening will not be allowed to enroll during acute phase. * Active substance abuse or significant psychiatric illness that in the opinion of the investigator might interfere with study compliance. * Use of any investigational agents 30 days prior to screening * Life expectancy \< 6 months in the opinion of the investigator * Prior use of darunavir or known allergy to any of the components of darunavir * Breast feeding * Female subject of childbearing potential not using effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until the last trial related activity. Note: Hormonal based contraception may not be reliable when taking darunavir, therefore to be eligible for this study, women of childbearing potential who may have vaginal intercourse should either: 1. Use a double barrier method to prevent pregnancy (i.e., using a condom with either a diaphragm or cervical cap) Or 2. Use hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or 3. Use an intra uterine device (IUD) in combination with a barrier contraceptive (i.e., male condom, diaphragm, cervical cap or female condom) Or 4. Be non-heterosexually active, practice sexual abstinence or have a vasectomized partner (confirmed sterile).