SYMTUZA - Effect on Body Composition

SUMMARY

• The DEFINE study (NCT04442737) was a phase 4, 48-week, prospective, randomized, active-controlled, open-label trial that was conducted to determine whether switching to SYMTUZA reverses or reduces weight gain associated with integrase strand transfer inhibitor (INSTI) + tenofovir alafenamide (TAF)/emtricitabine (FTC) regimens in virologically suppressed adults with human immunodeficiency virus type 1 (HIV-1) and ≥10% weight gain (N=103).¹
  • Changes in body composition were minor across all body compartments at week 24 in SYMTUZA and INSTI + TAF/FTC treatment groups.

CLINICAL DATA

DEFINE

The DEFINE study was a phase 4, 48-week, prospective, randomized, active-controlled, open-label trial that was conducted to determine whether switching to SYMTUZA reverses or reduces weight gain associated with INSTI + TAF/FTC regimens in virologically suppressed adults with HIV-1 and ≥10% weight gain (N=103).¹ 

Study Design

• 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.
• The primary endpoint was the percent change in body weight from baseline at week 24.
• 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

• 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, 63% were Black, 37% were White, and 16% were Hispanic or Latino.
• In the SYMTUZA cohort and the INSTI + TAF/FTC cohort, the median BMI was 31.4 (range: 21.6-61.4) kg/m² and 34.7 (range: 21.5-57.8) kg/m², respectively.
• The median body weight was 94.5 (range: 68.8-188.4) kg in SYMTUZA group and 102.9 (range: 69.9-188.0) kg. At baseline, the percent of weight gain on current regiment was observed in the 12.8% of patients in SYMTUZA group and 15.7% in INSTI + TAF/FTC group.
• At week 24, there was no significant difference in the least-square (LS) mean percent change in body weight from baseline between patients in the SYMTUZA group and those in the INSTI + TAF/FTC group (0.63%; [95% confidence interval [CI], -0.44 to 1.70] and -0.24% [95% CI, -1.35 to 0.87], respectively).
• In the SYMTUZA group, a decrease in body weight was observed from baseline to week 48 with the extended time post-antiretroviral (ARV) switch (-0.36%; 95% CI, -‍1.77 to 1.06).
• The median change in the absolute body weight from baseline to week 24 in the SYMTUZA group and the INSTI + TAF/FTC group was 0.50 kg (interquartile range [IQR], -2.30 to 2.60) and 0.30 kg (IQR, -2.10 to 2.30), respectively.
• 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.
• Both treatment groups showed minimal changes in the BMI and waist circumference through week 24. See Table: Summary of Absolute BMI and Waist Circumference Measurements (Intent-to-Treat Population).

Body composition by DEXA at baseline, week 24, and week 48

• 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.
• Percentage of fat for trunk: At baseline, the median percentage of fat in the trunk region was 41.1% (IQR, 31.4-47.2) in the SYMTUZA group and 46.0% (IQR, 40.5–51.3) in the INSTI + TAF/FTC group. At week 24, these values were 40.3% (IQR, 29.8-47.3) in SYMTUZA group and 47.5 (IQR, 40.0-50.8) in INSTI + TAF/FTC group.
• Percentage of fat for extremities: In the SYMTUZA and INSTI + TAF/FTC groups, the median percentage of fat for extremities at baseline was 63.2% (IQR, 44.8-88.6) and 71.7% (IQR, 62.2-89.4), respectively. At week 24, these values were 62.3% (IQR, 49.3-88.2) in SYMTUZA group and 69.5% (IQR, 62.5-91.7) in INSTI + TAF/FTC group.
  • At week 48, the SYMTUZA group showed median fat percentages of 47.5% (IQR, 40.0–50.8) in the trunk and 69.5% (IQR, 62.5–91.7) in the extremities.
• Lean body mass for total body: In the SYMTUZA and INSTI + TAF/FTC groups, the median lean body mass for total body at baseline was 53.3 kg (IQR, 46.2-63.9) and 57.6 kg (IQR, 52.4-63.5), respectively. At week 24, the values were 52.5 kg (IQR, 47.2-62.2) in SYMTUZA group and 57.7 kg (IQR, 48.5 to 66.5) in INSTI + TAF/FTC group.
• Lean body mass for extremities: The median lean body mass of the extremities at baseline was 24.6 kg (IQR, 22.1–29.6) in the SYMTUZA group and 25.9 kg (IQR, 22.7–30.3) in the INSTI + TAF/FTC group. At week 24, these values were 23.6 kg (IQR, 21.9–28.7) in the SYMTUZA group and 26.0 kg (IQR, 23.4–29.8) in the INSTI + TAF/FTC group.
  • At week 48, the SYMTUZA group showed median lean body mass of 54.9 kg (IQR, 47.7-62.4) for the total body and 25.5 kg (IQR, 21.6-28.9) for the extremities.
• Estimated visceral adipose tissue (VAT) area: In the SYMTUZA and INSTI + TAF/FTC groups, the median VAT area at baseline was 148.3 cm² (IQR, 117.8-223.4) and 197.4 (IQR, 121.8-260.9), respectively. At week 24, the values were 136.2 cm² (IQR, 93.0-202.9) in SYMTUZA group and 203.4 cm² (IQR, 145.7-280.1) in INSTI + TAF/FTC group.
  • The VAT/extremities fat ratio was 0.086 at baseline, 0.084t week 24, and 0.085 at week 48. The trunk/ extremities fat mass ratio was 1.331 at baseline, 1.268 at week 24, and 1.296 at week 48.

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 03 July 2025.