Phase 4
Completed N=60
DRIVESHAFT: Darunavir/Ritonavir In HIV-infected Virologically-suppressed Experienced Subjects
Source: ClinicalTrials.gov NCT01423812 ↗Enrolled (actual)
60
Serious AEs
0.0%
Results posted
Feb 2018
Primary outcomePrimary: Primary Efficacy Endpoint for Virologic Suppression in HIV-infected Subjects — 27; 25 participants
◆ Published Evidence
Emerging
3citations · ~0 / year
Simplification from twice-daily to once-daily darunavir/ritonavir in a randomized trial among HIV-infected persons with HIV-1 RNA suppression on antiretroviral therapy.
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.
Linked Publications
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Simplification from twice-daily to once-daily darunavir/ritonavir in a randomized trial among HIV-infected persons with HIV-1 RNA suppression on antiretroviral therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Primary Efficacy Endpoint for Virologic Suppression in HIV-infected Subjects |
27; 25 | — |
| SECONDARY Secondary Efficacy Endpoints |
29; 25 | — |
| SECONDARY Change in Total Cholesterol From Baseline to 48 Weeks |
-14.2; -3.8 | <0.05 sig |
| SECONDARY Absolute Value Change in CD4+ From Baseline to Week 48 |
19; 39 | <0.05 sig |
| SECONDARY Assessment of Virologic Failure |
0; 0 | — |
| SECONDARY Number of Participants With Greater Than 95% Adherence at 48 Weeks |
22; 20 | — |
Eligibility Criteria
Inclusion Criteria
- ART-experienced, HIV-1 infected subjects ≥18 years of age.
- A female subject is eligible to enter and participate in the study if she:
- 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,
- 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 50 cells/mm3
- HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen
- Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals
- Negative serum pregnancy test at screening visit
Exclusion Criteria
Subjects meeting any of the following criteria must not be enrolled in the study:
- Known hypersensitivity reaction to agents being utilized in the study
- >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
- Pregnant or breast feeding woman
- Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis
Data sourced from ClinicalTrials.gov (NCT01423812) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.