DRIVESHAFT: Darunavir/Ritonavir In HIV-infected Virologically-suppressed Experienced Subjects
Condition: HIV
Intervention: Twice-daily combination Darunavir and ritonavir; Once-daily combination Darunavir and ritonavir
Intervention description: Subjects randomized 1:1 to remain on regimens containing combination Darunavir 600mg plus Ritonavir 100mg twice-daily; Subjects randomized 1:1 to switch to from combination Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to the experimental combination Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks
Intervention MeSH terms: Ritonavir; Darunavir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; treatment-experienced; protease inhibitor; adherence; lipids

Summary:

      Darunavir is a nonpeptidic protease inhibitor with a high genetic barrier to resistance that
      evolved from a prototype compound synthesized using structure-based design strategies.
      Once-daily darunavir at 800mg boosted with 100mg of ritonavir is an effective antiretroviral
      agent indicated for HIV-infected treatment-naïve patients. In treatment-experienced patients,
      darunavir was initially approved for twice-daily administration boosted with twice-daily
      ritonavir at 600mg and 100mg, respectively. Recently, once-daily darunavir/ritonavir was
      approved for use in treatment-experienced adult patients with viremia with no darunavir
      resistance mutations. In treatment-experienced patients with viral suppression, switching
      from an antiretroviral taken twice-daily to a once-daily dose is an attractive option to
      promote greater patient acceptability and adherence, and potentially minimize side effects
      and toxicities. Because of darunavir/ritonavir's high genetic barrier to resistance and
      well-established safety profile at a once-daily dose, switching patients with virologic
      suppression from twice-daily darunavir/ritonavir to once-daily darunavir/ritonavir will
      likely confer attributes more favorable to patients through a simplified dosing schedule and
      lower potential for lipid elevation without the loss of virologic control. DRIVESHAFT is a
      48-week Phase 4, randomized, open label, comparative study. The study will be conducted in 60
      HIV-1 infected, antiretroviral experienced, virologically-suppressed patients on regimens
      containing darunavir 600mg/ ritonavir 100mg twice-daily and a minimum of two other
      antiretrovirals, with a history of 0-1 darunavir-associated resistance mutations. Subjects
      will be randomized 1:1 to switch to darunavir 800mg/ ritonavir 100mg once-daily or continue
      on their current regimen. Rates of virologic suppression of once-daily darunavir/ritonavir
      regimens relative to darunavir/ritonavir twice-daily regimens will be compared, and safety,
      change from baseline fasting lipid parameters, and adherence will be evaluated.
    

Eligibility criteria:

        Inclusion Criteria:

          1. ART-experienced, HIV-1 infected subjects ≥18 years of age.

          2. A female subject is eligible to enter and participate in the study if she:

               1. is of non-childbearing potential defined as either post-menopausal (12 months of
                  spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming
                  pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy
                  or,

               2. is of child-bearing potential, with a negative pregnancy test at both Screen and
                  Day 1 and agrees to one of the following methods of contraception to avoid
                  pregnancy:

                    -  Complete abstinence from intercourse from 2 weeks prior to administration of
                       study medications, throughout the study, and for at least 2 weeks after
                       discontinuation of all study medications.

                    -  Double barrier method (male condom/spermicide, male condom/diaphragm,
                       diaphragm/spermicide).

                    -  Approved hormonal contraception may be administered with darunavir/ritonavir

                    -  Any intrauterine device (IUD) with published data showing that the expected
                       failure rate is <1% per year

                    -  Any other method with published data showing that the expected failure rate
                       is <1% per year.

             Any contraception method must be used consistently and in accordance with the approved
             product label. All subjects participating in the study should be counseled on safer
             sexual practices including the use of effective barrier methods (e.g. male
             condom/spermicide).

          3. CD4 >50 cells/mm3

          4. HIV-1 RNA concentrations at undetectable levels (according to local assay being used)
             for at least 12 weeks on stable current regimen

          5. Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of
             two other antiretrovirals

          6. Negative serum pregnancy test at screening visit

        Exclusion Criteria:

        Subjects meeting any of the following criteria must not be enrolled in the study:

          1. Known hypersensitivity reaction to agents being utilized in the study

          2. >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M,
             T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1
             darunavir fold-change >10.0 on any previous virtual phenotype

          3. Pregnant or breast feeding woman

          4. Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis