Safety Information of SYMTUZA - Effect on Lipids

SUMMARY

• In the AMBER study, there was a statistically significant increase in all lipid parameters from baseline to week 48.¹ In the SYMTUZA arm, lipid-lowering drugs were started by 6 (1.7%) and 14 (4%) of patients by weeks 48 and 96, respectively.²
• In the EMERALD study, lipid-lowering drugs were started by 20/763 (3%) patients in the SYMTUZA arm vs. 7/378 (2%) patients in the boosted protease inhibitor (bPI) arm by week 48,³ and by 59/763 (8%) patients in the SYMTUZA arm vs. 19/352 (5%) patients in the control arm by week 96.⁴
• In the GS-US-299-0102 study, there were greater increases in fasting lipid parameters in the SYMTUZA arm compared with the darunavir (DRV)+ cobicistat (COBI)+ emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) arm at week 48.⁵
• In the DETOX study, there was a significant increase in triglycerides, low-density lipoprotein (LDL) cholesterol, and total cholesterol from baseline to week 8, whereas high-density lipoprotein (HDL) cholesterol remained stable.⁶

CLINICAL DATA

AMBER

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

Study Design/Methods

• Patients were stratified by screening viral load (VL;< / ≥100,000) and by screening cluster of differentiation (CD) 4+ cell counts (< / ≥200 cells/mm³) and then randomized to a single-tablet regimen (STR) of SYMTUZA (DRV 800 mg, COBI 150 mg, FTC 200 mg, and tenofovir alafenamide [TAF] 10 mg) with matching DRV/COBI + FTC/TDF placebo or the active-control regimen of DRV/COBI + FTC/TDF with a matching SYMTUZA placebo.
• After database lock and unblinding for the week 48 analysis, patients randomized to SYMTUZA continued on open-label SYMTUZA and patients randomized to the DRV/COBI + FTC/TDF control arm were switched to SYMTUZA 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, see Table: Median (IQR) Change from Baseline in Fasting Lipids at Week 48.
• There were 6 (1.7%) patients in the SYMTUZA arm who started lipid lowering therapy compared to 2 (0.6%) patients in the control arm.

Results-Week 96²

• In the SYMTUZA 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).
• Grade 3 or 4 fasting LDL-cholesterol (≥190 mg/dL [4.90 mol/L]) occurred in 9% (30/346) of patients in the SYMTUZA arm from baseline-week 96 and 4% (11/295) of patients in the control arm after switch to SYMTUZA.
• Fasting lipid parameters are shown in Table: Fasting Lipids.
• Lipid-lowering drugs were started by 14 (4%) patients by week 96 in the SYMTUZA arm and 3 (1%) of patients in the control arm after switch to SYMTUZA.

EMERALD

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

Study Design/Methods

• Patients were stratified according to PI (DRV/ritonavir [r] or DRV/COBI once daily [QD], atazanavir [ATV]/r or ATV/COBI QD, or lopinavir [LPV]/r twice daily [BID]) and then randomized 2:1 to switch to SYMTUZA or to continue their bPI regimen.
• After week 48, patients randomized to SYMTUZA continued on SYMTUZA and patients randomized to the bPI arm were switched to SYMTUZA in the extension phase until week 96.⁴

Results-Week 48³

• Median changes from baseline to week 48 (SYMTUZA vs. bPI):
  • 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 SYMTUZA arm vs. 7/378 (2%) patients in the bPI arm (P=0.54).
• For treatment emergent AEs, see Table: Treatment-Emergent Grade 3-4 Laboratory AEs (≥3% in Either Arm).

Results-Week 96⁴

• 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 SYMTUZA arm, fasting lipid parameters remained stable after week 48.
• By week 96, lipid-lowering drugs were started by 59/763 (8%) patients in the SYMTUZA arm vs. 19/352 (5%) patients in the control arm.

GS-US-299-0102

In the GS-US-299-0102 study, the efficacy and safety of the SYMTUZA STR was compared to that of DRV + COBI (administered as single agents) + FTC/TDF in HIV-1 infected, treatment-naïve patients (N=153).⁵

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 an STR containing SYMTUZA (DRV 800 mg, COBI 150 mg, FTC 200 mg, and TAF 10 mg) [TAF arm]), or a regimen consisting of DRV 400 mg x 2 + COBI 150 mg + FTC/TDF 200/300 mg tablets (TDF arm).

Results

• There were greater increases in fasting lipid parameters in the TAF arm compared with the TDF arm at week 48, see 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).

DETOX

DETOX was a randomized, open-label study that was conducted in 2 phases to evaluate whether switching from dolutegravir (DTG)/lamivudine (3TC)/abacavir (ABC) to SYMTUZA could help in improving the quality of sleep, mood, and neuropsychiatric status in virologically-suppressed, human immunodeficiency virus (HIV)-infected adults.⁶

Study Design/Methods

• Phase 1: Patients were randomized to switch at baseline from DTG/3TC/ABC to SYMTUZA (immediate switch arm; n=37) or to continue 4 weeks with DTG/3TC/ABC and then switch to SYMTUZA (deferred switch arm; n=35).
• Phase 2: Patients from both the arms completed 8 weeks of follow-up after switching to SYMTUZA.
• Patients with HIV who had no major neuropsychiatric comorbidities (major depression with psychotic symptoms or suicidal ideation, drug abuse/dependence, dementia, or psychosis), were receiving DTG/3TC/ABC for at least 4 weeks, had poor quality of sleep (PSQI score >5), and did not complain of insomnia were included.
• Changes in lipid parameters were evaluated as part of the safety analysis.

Results

• From baseline to week 8, a significant increase in total cholesterol, LDL cholesterol, and triglycerides was observed, whereas HDL cholesterol remained stable (see Table: Mean Lipids Levels at Baseline, Week 4, and Week 8).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 17 July 2025.