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).