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

A Randomized, Controlled Trial to Evaluate the Efficacy of Substituting Darunavir/Ritonavir (DRV/r) for Dual-boosted Protease Inhibitors in Individuals With Virologic Suppression for at Least 12 Weeks

This study will evaluate patients who have achieved virologic suppression (< 400 copies/mL) on any dual protease inhibitor (PI) combination, to determine whether patients can substitute both PIs with the single boosted PI darunavir given 600/100 ritonavir (RTV) twice daily (BID) and maintain comparable virologic suppression (% < 50 c/mL) for 24 weeks.

The purpose of this study is to determine if patients who have achieved virologic suppression (< 400 copies/mL) on any dual PI combination, can substitute both PIs with the single boosted PI darunavir given 600/100 rtv bid and maintain comparable virologic suppression (% < 50 c/mL) for 24 weeks. Randomized, non-blinded, multicenter, 48 week, controlled trial to assess the non-inferiority of substituting DRV/r for a dual boosted PI combination in patients with stable virologic suppression on a regimen containing a dual boosted PI combination plus at least one additional FDA-licensed antiretroviral agent from another class. Participants will be randomized (1:1) to one of the included treatment arms.

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).