PREZCOBIX - Safety Information - Effect on Lipids

Summary

• In the GS-US-216-0130 study, no clinically relevant changes from baseline through week 48 in median fasting total cholesterol (TC), median fasting low-density lipoprotein cholesterol (LDL), median fasting high-density lipoprotein cholesterol (HDL), median fasting triglycerides (TG), or median fasting TC to HDL ratio were observed in patients who received darunavir (DRV) and cobicistat (COBI).^1-3
• A study conducted in virologically suppressed patients who were receiving a stable regimen containing darunavir (DRV)/ritonavir (r) and were then switched from ritonavir to COBI found that COBI had a beneficial effect on TG levels in all patients. Statistically significant changes in all lipid parameters were observed in patients with baseline hypercholesterolemia.⁴
• In the AMBER study, which compared PREZCOBIX + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) with the single-tablet regimen (STR) DRV/COBI/FTC/tenofovir alafenamide (TAF), there was a statistically significant increase in all lipid parameters from baseline to week 48. Lipid-lowering drugs were started by 6 (1.7%) patients in the STR arm and 2 (0.6%) patients in the PREZCOBIX arm by week 48, and 14 (4%) patients in the STR arm vs. 3 (1%) patients in the PREZCOBIX arm by week 96.^5,6
• In the GS-US-299-0102 study, there were greater increases in fasting lipid parameters in the STR (DRV/COBI/FTC/TAF) group compared with the DRV + COBI + FTC/TDF group at week 48.⁷
• In the EMERALD study, lipid-lowering drugs were started by 20/763 (3%) patients in the STR (DRV/COBI/FTC/TAF) arm vs. 7/378 (2%) patients in the boosted protease inhibitor (bPI) + FTC/TDF arm by week 48, and by 59/763 (8%) patients in the STR arm vs. 19/352 (5%) patients in the control arm by week 96.^8,9

clinical Studies

GS-US-216-0130 Study

GS-US-216-0130 is a phase 3b, open-label, single arm, 48 week, multicenter US study evaluating the safety, tolerability, efficacy, and pharmacokinetics of DRV 800 mg + COBI 150 mg once daily (QD; administered as single agents) in combination with 2 fully active nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-naïve and treatment-experienced (no DRV RAMs) HIV-1-infected patients (N=313; n=295 treatment-naïve).¹

Lipid Evaluations

Week 24-Lipids

• Through week 24, 4 patients (1.3%) each experienced hypercholesterolemia and hypertriglyceridemia, and 3 patients (1.0%) experienced increased blood TG.²
  • All but 1 of these patients (hypertriglyceridemia) were treatment-naïve.
  • A total of 3 patients experienced grade 3 hypercholesterolemia, and a total of 4 patients experienced a grade 3 increase in TG. All of these patients were treatment-naïve.
  • No subject experienced a serious adverse event (AE) associated with a clinical laboratory abnormality, and no subject discontinued with study drugs or the study due to an AE associated with a clinical laboratory abnormality.
• There were no clinically relevant changes from baseline through week 24 observed in either the treatment-naïve or treatment-experienced cohorts for median fasting TC, median fasting LDL, median fasting HDL, median fasting TG, or median fasting TC to HDL ratio.²
• There were no apparent relationships observed between DRV area under the concentration-time curve during a 24-hour interval (AUC_24h) and worst toxicity grade in TC, LDL, HDL, or TG through week 24.²
  • Higher DRV AUC_24h and trough plasma concentrations (C_0h) were observed in patients with grade 3 cholesterol changes. This analysis was limited by a small sample size (n=4).

Week 48-Lipids

• There were no clinically relevant changes from baseline in median lipid parameters through week 48.¹

Echeverria Study

Echeverria et al (2017)⁴ evaluated changes in lipid parameters and the percentage of subjects with dyslipidemia in virologically suppressed HIV-1 infected patients who were receiving a stable regimen containing DRV/r (monotherapy, dual therapy, or triple therapy for ≥6 months) and were then switched from ritonavir to COBI (N=299).

Study Design/Methods

• Retrospective observational study.
• Lipid parameters at baseline before the switch and 24 weeks after the switch were compared.
• Patients were stratified according to the presence of hypercholesterolemia (taking lipid-lowering drugs or baseline TC >200 mg/dL and/or LDL >130 mg/dL) or hypertriglyceridemia (baseline TG levels >200 mg/dL).

Results

Baseline Characteristics

• Epidemiological, clinical, and human immunodeficiency virus (HIV)-related characteristics are summarized in Table: Baseline Characteristics.
• Fifty-two percent of patients had dyslipidemia (hypercholesterolemia and/or hypertriglyceridemia) at baseline; of these, 52% were on monotherapy, 61% were on dual therapy, and 70% were on triple therapy.

Lipid Evaluations

• Changes in lipid parameters are detailed in Table: Changes in Lipid Parameters at Week 24.
• In the study population as a whole or in the subset with baseline hypertriglyceridemia, only TG decreased significantly from baseline; significant changes in other lipids were not observed.
• In the subset with baseline hypercholesterolemia, changes from baseline to week 24 were significant for all lipid parameters.

Data from Studies with drv/cobi/ftc/taf Str

AMBER

The AMBER study is a phase 3, randomized, active-controlled, double-blind study to evaluate efficacy and safety of the STR DRV/COBI/FTC/TAF vs. the fixed-dose combination PREZCOBIX co-administered with FTC/TDF in antiretroviral (ARV) treatment-naïve HIV-1-infected adults (N=725).⁵

Study Design/Methods

• Patients were stratified by screening viral load (VL;</≥100,000) and by screening CD4+ cell counts (</≥200 cells/mm³) and then randomized to receive the STR (DRV 800 mg, COBI 150 mg, FTC 200 mg, and TAF 10 mg) with matching PREZCOBIX + FTC/TDF placebo or the active-control regimen of PREZCOBIX + FTC/TDF with a matching STR placebo.
• After database lock and unblinding for the week 48 analysis, patients randomized to the STR continued on open-label DRV/COBI/FTC/TAF and patients randomized to the PREZCOBIX + FTC/TDF control arm were switched to DRV/COBI/FTC/TAF in the extension phase until week 96.

Results – Week 48

• There was a statistically significant increase in all lipid parameters from baseline to week 48 (Table. Median (Interquartile Range [IQR]) Change from Baseline in Fasting Lipids at Week 48).⁵
• There were 6 (1.7%) patients in the STR arm who started lipid lowering therapy compared to 2 (0.6%) patients in the PREZCOBIX + FTC/TDF arm.

Results – Week 96

• In the initial STR arm, there were statistically significant increases from baseline to week 96 in fasting total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and total cholesterol/HDL-cholesterol ratio (P<0.001 for within treatment arm changes).⁶
• Grade 3 or 4 fasting LDL-cholesterol (≥190 mg/dL [4.90 mol/L]) occurred in 9% (30/346) of patients in the STR arm from baseline-week 96 and 4% (11/295) of patients in the PREZCOBIX + FTC/TDF arm after switch to the STR.
• Fasting lipid parameters are shown in Table: Fasting Lipids.
• Lipid-lowering drugs were started by 14 (4%) patients by week 96 in the STR arm and 3 (1%) of patients in the PREZCOBIX + FTC/TDF arm after switch to the STR.

GS-US-299-0102

In the GS-US-299-0102 study, the efficacy and safety of the DRV/COBI/FTC/TAF STR was compared to that of DRV + COBI (administered as single agents) + FTC/TDF in HIV-1 infected, treatment-naïve patients (N=153).⁷

Study Design/Methods

• Patients were stratified by baseline VL (≤100,000 and >100,000) and race (black and non-black) and randomized 2:1 to receive the STR (DRV 800 mg, COBI 150 mg, FTC 200 mg, and TAF 10 mg; TAF group) or a regimen consisting of DRV 400 mg x 2 + COBI 150 mg + FTC/TDF 200/300 mg tablets (TDF group).

Results

• There were greater increases in fasting lipid parameters in the TAF group compared with the TDF group at week 48 (Table: Median Change from Baseline in Fasting Lipids at Week 48).
• The majority of reported lipid-related adverse events and laboratory abnormalities were nonserious and mild in severity.
• There were no differences in the number of patients who were initiated on lipid-lowering medications during the study (TAF, 7 [6.8%] vs. TDF, 4 [8%], P=0.75).

EMERALD

The EMERALD study is a phase 3, randomized, active-controlled, open-label study to evaluate the efficacy, safety, and tolerability of switching to the DRV/COBI/FTC/TAF STR vs. continuing the current regimen consisting of a bPI combined with FTC/TDF in virologically-suppressed, HIV-1-infected adults (N=1141).⁸

Study Design/Methods

• Patients were stratified according to PI (DRV/r or PREZCOBIX QD, atazanavir [ATV]/r or ATV/COBI QD, or lopinavir [LPV]/r BID) and then randomized 2:1 to switch to the STR (DRV 800 mg, COBI 150 mg, FTC 200 mg, and TAF 10 mg) or to continue their bPI regimen.
• After week 48, patients randomized to the STR continued on DRV/COBI/FTC/TAF and patients randomized to the bPI arm were switched to DRV/COBI/FTC/TAF in the extension phase until week 96.⁹

Results- Week 48

• Median changes from baseline to week 48 (STR vs. bPI + FTC/TDF):⁸
  • Fasting total cholesterol: 19.7 mg/dL vs. 1.3 mg/dL (P<0.0001)
  • LDL-cholesterol: 15.7 mg/dL vs. 1.9 mg/dL (P<0.0001)
  • Ratio of total cholesterol to HDL-cholesterol: 0.2 vs. 0.1 (P=0.010)
• During treatment, lipid-lowering drugs were started by 20/763 (3%) patients in the STR arm vs. 7/378 (2%) patients in the bPI arm (P=0.54).

Results – Week 96⁹

• Treatment-emergent grade 3 or 4 laboratory abnormalities are shown in Table. Most Common Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities (>5% Either Arm).
• Median change in fasting lipid parameters are shown in Table. Median (IQR) Change in Fasting Lipids.
• In the initial STR arm, fasting lipid parameters remained stable after week 48.
• By week 96, lipid-lowering drugs were started by 59/763 (8%) patients in the initial STR arm vs. 19/352 (5%) patients in the late switch arm.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 28 March 2025. Company-sponsored studies and studies specifically evaluating DRV/COBI and effect on lipid parameters were included.