Effectiveness of Switching to Darunavir/Cobicistat in Virologically Suppressed HIV-Positive Patients Receiving Ritonavir-Boosted Protease Inhibitor–Based Regimen

The 'STORE' Study

Andrea Gori, MD; Andrea Antinori, MD; Alessandra Vergori, MD; Maria Vittoria Cossu, MD; Barbara Menzaghi, MD; Gaetana Sterrantino, MD; Stefano Rusconi, MD; Anna Maria Cattelan, MD; Francesco Castelli, MD, PhD; Nicola Gianotti, MD; Giancarlo Orofino, MD; Diego Ripamonti, MD; Stefano Savinelli, MD; Elio Manzillo, MD; Teresa Antonia Santantonio, MD; Benedetto Maurizio Celesia, MD; Roberto Cauda, MD, PhD; Renato Maserati, MD; Antonella d'Arminio Monforte, MD; Christof Stingone, MD; Stefano Bonora, MD; Alessia Uglietti, MD, PhD; Roberta Termini, PharmD; Francesco Rucci, MD; Daniela Mancusi, MSc


J Acquir Immune Defic Syndr. 2020;84(3):290-294. 

In This Article

Abstract and Introduction


Objective: This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated.

Setting: Prospective, multicenter, single-country, noninterventional cohort study.

Methods: This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA <50 copies/mL since at least 6 months. The primary endpoint, defined as HIV-1 RNA <50 copies/mL, was measured at 48 ± 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response algorithm. Biochemical parameters, including DRV trough samples, were collected as per clinical practice and measured using high-performance liquid chromatography.

Results: Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA <50 copies/mL at 48 weeks; using the time to loss of virological response algorithm, 82.7% maintained virological suppression. Virological failure was observed in 6 patients (1.8%). Adverse event–related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130 to 113.5 mg/dL, P = 0.0254) and high-density lipoprotein cholesterol (48 to 49 mg/dL, P < 0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5–4439) ng/mL, higher in women than in men (4221 vs. 2634 ng/mL, P = 0.046).

Conclusions: In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of virological failure and adverse events due to its high tolerability and improvement in triglycerides.


The current treatment of HIV-positive patients requires lifelong administration of combination antiretroviral (ARV) drugs, which is extremely effective and well tolerated, but several factors may decrease its long-term efficacy. As patient adherence is crucial to maintain the efficacy and immunological benefits of ARV treatment,[1] it is essential to adopt effective and well-tolerated ARV strategies, including a reduced number of pills. Regarding this latter point, the adoption of fixed-dose combinations and single-tablet regimens has a decisive role in improving patient compliance and adherence to antiretroviral therapy (ART).[2]

For the above reason, a coformulation of the protease inhibitor (PI) darunavir (DRV) with the pharmacoenhancer cobicistat has been developed.[2] Cobicistat, at the dose of 150 mg once a day, while not having antiviral activity, is more selective in terms of enzyme inhibition, thus reducing the number of clinically relevant drug-drug interactions compared with the previous pharmacoenhancer ritonavir (RTV).[3] This fixed-dose combination, reducing the pill burden, allows to improve adherence to ART.[4] To date, few clinical trials have studied DRV/c in a real-world clinical setting. Most data on DRV/c were obtained from the phase 3 Study GS-US-216-0130,[5] but real-life data were available only in 2017.[6]

The primary aim of this study was to describe the effectiveness of DRV/c-based regimens in terms of maintenance of virological suppression after 48 ± 6 weeks from study enrollment. Furthermore, we described steady-state DRV trough values in a subgroup of patients, if collected per clinical practice.