SYMTUZA - DEFINE Study

SUMMARY

• The DEFINE study is a multicenter, randomized, open-label, parallel assignment phase 4 study to evaluate the effect of switching to SYMTUZA in virologically suppressed adults with HIV-1 who have experienced ≥10% increase in body weight within a 36-month period on an integrase strand transfer inhibitor (INSTI) + tenofovir alafenamide/emtricitabine (TAF/FTC; NCT04442737).¹
  • Patients were randomized to switch immediately to SYMTUZA once daily for 48 weeks or to remain on their current regimen for 24 weeks, after which they will switch to SYMTUZA for an additional 24 weeks.
  • The primary endpoint was the percent change in body weight from baseline at week 24.
• At week 24, in the intent-to-treat (ITT) population, there was no significant difference in the percent change in body weight from baseline between patients in the SYMTUZA group (0.63 [-0.44, 1.70]) and those in the INSTI + TAF/FTC group (-0.24 [1.35, 0.87]).¹
• At week 24, the percent change in body weight from baseline was consistent among various subgroups (body mass index [BMI] ≥30 kg/m²) in both study groups.¹
• The most frequently reported adverse events (AEs) in the SYMTUZA group were coronavirus disease 2019 (COVID-19; 11%), diarrhea (6%), nausea (6%), and hypertension (2%).¹

CLINICAL DATA

DEFINE STUDY

The DEFINE study is a multicenter, randomized, open-label, parallel assignment phase 4 study conducted in virologically suppressed adults with HIV-1 who have experienced ≥10% increase in body weight within a 36-month period on an INSTI + TAF/FTC to determine if a switch to SYMTUZA results in a change in body weight (N=103).¹

Study Design/Methods

• Patients were randomized 1:1 to switch immediately to SYMTUZA (darunavir 800 mg/ cobicistat 150 mg/FTC 200 mg/TAF 10 mg) once daily for 48 weeks or remain on their current regimen for 24 weeks and then switched to SYMTUZA for an additional 24 weeks. ^1,2
• The primary endpoint was the percentage change in body weight from baseline at week 24.
• The secondary metabolic outcomes included changes in body mass index (BMI), waist circumference, body composition, laboratory findings of glucose/lipid metabolism, and liver biomarkers.
• Body composition was measured by dual X-ray absorptiometry at baseline, week 24, and week 48 in both SYMTUZA and INSTI + TAF/FTC treatment groups.
• Data were reported for both treatment groups through week 24, with extended time data reported through week 48 for the SYMTUZA group.

Results

Baseline Characteristics

• Overall, 103 patients were included in the study and were randomly assigned to one of two treatment groups: 53 patients to the SYMTUZA group and 50 patients to INSTI + TAF/FTC groups.
• The median age was 45 years (range, 22-73); 30% of patients were female, 61% were Black/African American, 37% were White, and 16% were Hispanic or Latino. See Table: Key Baseline Demographics and Characteristics (ITT Set).²

Weight and Body Composition²

• At week 24, there was no significant difference in the least-square mean percent change in body weight from baseline in the SYMTUZA vs INSTI + TAF/FTC group (0.63 [-0.44 to 1.70] vs -0.24 [-1.35 to 0.87]; P=0.24).
• In the SYMTUZA treatment group, a decrease in body weight was observed from baseline to week 48 with an extended time post-ARV switch (-0.36%; 95% confidence interval, -1.77 to 1.06).
• The median (interquartile range [IQR]) change in the absolute body weight from baseline to week 24 was 0.50 kg (-2.30 to 2.60) in the SYMTUZA group and 0.30 kg (-2.10 to 2.30) in the INSTI + TAF/FTC group.
• In the SYMTUZA group, a reduction in body weight was noted over time following the ARV switch, with a median change of -0.85 kg (IQR, -4.50 to 1.70) from baseline to week 48.
• At week 24, there were minimal differences between the treatment groups in patients who experienced >5% weight loss.
• In the SYMTUZA group, patients experienced an increase in clinically meaningful weight loss over the extended time post-ARV switch, with 4% vs 24% of patients experiencing >5% weight loss at week 24 vs week 48.
• Both treatment groups showed minimal changes in BMI and waist circumference through week 24. See Table: Summary of Absolute BMI and Waist Circumference Measurements (Intent-to-Treat Population).

Body Composition by Dual-Energy X-ray Absorptiometry at Baseline, Week 24, and Week 48¹

• At baseline, the median total body fat percentage was 36.7% (IQR, 27.4-43.2) in the SYMTUZA group and 40.5% (IQR, 35.5-47.9) in the INSTI + TAF/FTC group.
• At week 24, the total body fat percentage in the SYMTUZA group and the INSTI + TAF/FTC group was 35.5% (IQR, 28.6-43.7) and 39.5% (IQR, 35.7-46.4), respectively. In the SYMTUZA group, the median total body fat percentage was 36.3% (IQR, 28.3-42.9) at week 48.
• The lean body mass was largely maintained throughout the study.
• Changes in body composition were minor across all body compartments at week 24 in both treatment groups. In the SYMTUZA group, these changes remained minimal with the extended time post-ARV switch. See Table: Body Composition Measurements by Dual X-ray Absorptiometry Over Time.

Safety

• Safety data throughout the study is reported in Table: Summary of Safety Report (Safety Analysis Set).¹
• The most frequently reported AEs in the SYMTUZA group were COVID-19 (11%), diarrhea (6%), nausea (6%), and hypertension (2%).¹

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 11 August 2025.