DRIVESHAFT: Darunavir/Ritonavir In HIV-infected Virologically-suppressed Experienced Subjects

The Darunavir/Ritonavir In Virologically-suppressed Experienced Subjects Halving an Antiretroviral by Finetuning Therapy (DRIVESHAFT) study was a prospective, randomized, single-centre, two-arm, open-label 48-week pilot study. The aim of DRIVESHAFT was to evaluate the safety and efficacy of switching the DRV/r component from twice-daily to once-daily 800/100 mg compared with those remaining on current therapy among HIV-1-infected, treatment-experienced patients with 0-1 DRV RAMs on a stable regimen including twice-daily DRV/r 600/100 mg. The study was conducted at The Ruth M Rothstein CORE Center (Chicago, IL, USA). The sample size was determined upon feasibility as a single-site study and not powered for non-inferiority. Study enrolment was planned for 60 participants randomized 1:1 to one of two arms: the switch arm from DRV/r 600/100 mg twice daily to DRV/r 800/100 mg once/daily plus current ARV regimen including a minimum of two other agents or remain on current ARV regimen with minimum of three agents inclusive of twice-daily DRV/r. Two DRV 400 mg tablets were used in the once-daily DRV/r arm, with DRV 600 mg tablets administered in the twice-daily DRV/r arm.

DRIVESHAFT inclusion criteria included HIV-1-infected adult (>18 years of age), HIV-1 RNA measurements <40 copies/ml (using a local assay) over at least 12 weeks on a stable regimen including DRV/r 600/100 mg twice daily plus a minimum of two other ARVs, screening HIV-1 RNA<40 copies/ml, have undergone genotypic testing at any time prior to starting current antiretroviral therapy (ART) with evidence of <2 cumulative DRV RAMs, CD4+ T-cell count >50 cells/mm3, and a negative serum pregnancy test at screening visit Participants who were randomized and received at least one dose of study medication were included in efficacy analysis, and the primary end point was the proportion of participants with HIV-1 RNA<40 copies/ml at week 48.

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 <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).

• CD4 >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