Trial Outcomes & Findings for Can INSTI-associated Weight Gain be Halted or Reversed With a Switch to Doravirine/Lamivudine/Tenofovir DF? (NCT NCT04665375)

Results Overview

The primary objective was to determine how many clinic patients with ≥10% weight gain on an INSTI would complete the study (48 weeks).

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

4 participants

Primary outcome timeframe

1 year

Results posted on

2025-07-16

Participant Flow

Participant milestones

Participant milestones
Measure	DOR/3TC/TDF 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Overall Study STARTED	4
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Can INSTI-associated Weight Gain be Halted or Reversed With a Switch to Doravirine/Lamivudine/Tenofovir DF?

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Canada	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Number of clinic patients who experienced ≥10% weight gain on an INSTI within the last 5 years.

The primary objective was to determine how many clinic patients with ≥10% weight gain on an INSTI would complete the study (48 weeks).

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=129 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Identify Number of Active Clinic Patients Who Completed the Study Protocol.	3 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Number of participants screened for the study.

Descriptive data. Reasons for study ineligibility (i.e., not meeting inclusion criteria or presence of one or more exclusion criteria) will be recorded by the study coordinator.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=7 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Identify Reasons for Study Ineligibility Among Clinic Patients on INSTI-containing Regimen Who Have Experienced Weight Gain. started semaglutide	1 Participants
Identify Reasons for Study Ineligibility Among Clinic Patients on INSTI-containing Regimen Who Have Experienced Weight Gain. did not meet weight gain threshold	1 Participants
Identify Reasons for Study Ineligibility Among Clinic Patients on INSTI-containing Regimen Who Have Experienced Weight Gain. greater than 5 years INSTI use	1 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Number of individuals who refused screening/participation in the study.

Descriptive data. Clinic patients who refuse to participate in the study will be asked an open-ended question by the study coordinator about main reason(s) for declining. Responses will be grouped by the following categories: fear of side effects, distrust of researchers, general concerns about research design, interference in everyday life or changes in routine, and social discrimination.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=7 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Identify Reasons for Study Refusal Among Clinic Patients on INSTI-containing Regimen Who Have Experienced Weight Gain.	0 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Participants who did not complete the study to week 48.

Factors will include age, gender, race, CD4 count, HIV viral load, prior enrollment in a study, history of injection drug use, and use of antidepressants.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=4 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Identify Factors Associated With Early Study Discontinuation. study closed to futility	1 Participants
Identify Factors Associated With Early Study Discontinuation. completed study to week 48	3 Participants

SECONDARY outcome

Timeframe: 1 year

Population: participants who completed study to week 48

Absolute weight (kg) at one year minus weight at baseline (kg).

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
To Determine the Change in Absolute Weight From Baseline to One Year Following the Switch to DOR/TDF/3TC.	5.0 kg Interval 0.0 to 7.5

SECONDARY outcome

Timeframe: 1 year

Population: participants who completed study to week 48

To determine the number of participants who experienced either an increase, decrease or no change in weight (weight at 1 year vs. weight at baseline) following the switch to DOR/TDF/3TC.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Number of Participants Who Experienced a Change in Weight After a Switch to DOR/TDF/3TC at 1 Year increased weight from baseline	0 Participants
Number of Participants Who Experienced a Change in Weight After a Switch to DOR/TDF/3TC at 1 Year decreased weight from baseline	2 Participants
Number of Participants Who Experienced a Change in Weight After a Switch to DOR/TDF/3TC at 1 Year no change in weight from baseline	1 Participants

SECONDARY outcome

Timeframe: 1 year

Population: participants who completed study to week 48

Change in waist circumference (value at 1 year minus value at baseline) will be reported. Waist circumference to be measured using a landmark just above the uppermost lateral border of the right ilium (under the participant's clothing). Measurement will be recorded to the nearest tenth of a centimeter at the end of the participant's normal expiration.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Change in Waist Circumference From Baseline to One Year Following the Switch to DOR/TDF/3TC. participant 1	-0.8 cm
Change in Waist Circumference From Baseline to One Year Following the Switch to DOR/TDF/3TC. participant 2	-1.1 cm
Change in Waist Circumference From Baseline to One Year Following the Switch to DOR/TDF/3TC. participant 3	1 cm

SECONDARY outcome

Timeframe: 1 year

Population: participants who completed study to week 48

Number of participants with a change in BMI category (BMI category at one year compared to BMI category at baseline) following the switch to DOR/TDF/3TC.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Number of Participants Who Experienced a Change in BMI Category After a Switch to DOR/TDF/3TC at One Year moved from obese to overweight BMI	1 Participants
Number of Participants Who Experienced a Change in BMI Category After a Switch to DOR/TDF/3TC at One Year no change in BMI category	2 Participants

SECONDARY outcome

Timeframe: 1 year

Population: participants who completed study to week 48

To determine the number of participants who maintain viral suppression (HIV RNA \< 50 copies/ml using Abbott RealTime HIV-1 assay) at 1 year after a switch to DOR/TDF/3TC.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Number of Participants Who Maintain HIV RNA<50 Copies/mL After a Switch to DOR/TDF/3TC at 1 Year	3 Participants

SECONDARY outcome

Timeframe: 1 year

Population: participants who completed study to week 48

Adverse event parameters graded according to severity: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (potentially life-threatening), Grade 5 (death) as assessed by the US DHHS NIH/NIAID Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, corrected version 2.1 (July 2017)

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Number of Patients With Treatment-related Adverse Events	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Population: participants who completed study to week 48

loss of percentage of total body fat (difference at one year minus from baseline) following the switch from the INSTI-containing regimen to DOR/TDF/3TC according to DXA body scans.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Loss of Percentage of Total Body Fat From Baseline to One Year	2.9 percentage change in total body fat Interval 1.5 to 3.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Population: participants who completed study to week 48

The Body Weight, Image and Self-Esteem (B-WISE) questionnaire is a validated 12-item, self-administered questionnaire that assesses body image and self-esteem related to weight gain. It was selected to assess impact of weight gain/change in our study. B-WISE scores range between 12-36; higher scores are indicative of better psychosocial adjustment (12-20 = severe; 21-28 = moderate; 29-36 = mild). The change in total B-WISE scores (value at one year minus value at baseline) will be calculated.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Change in Self-esteem Related to Body Image as Per the Body Image Questionnaire B-WISE at One Year Versus Baseline.	5 score on a scale Interval 1.0 to 11.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

The change in FRAM scores (value at one year minus baseline value) will be measured.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Population: participants who completed study to week 48

The change in fasting blood glucose (value at one year minus baseline value) will be measured.

Outcome measures

Outcome measures
Measure	DOR/3TC/TDF n=3 Participants 100mg of doravirine (DOR), 300mg of lamivudine (3TC), and 300mg of tenofovir disoproxil fumarate (TDF) DOR/3TC/TDF: switch antiretroviral regimen to doravirine/lamivudine/tenofovir disoproxil fumarate once daily for 1 year
Change in Fasting Glucose Values Following the Switch From the INSTI-containing Regimen to DOR/TDF/3TC	-1.6 mmol/L Interval -1.8 to -0.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

HOMA score: fasting plasma glucose (mmol/L) times fasting serum insulin (mU/L) divided by 22.5. A score of \<3 indicates normal insulin resistance, a score between 3 and -5 indicates moderate insulin resistance, and a score \>5 indicates severe insulin resistance.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Standard lipid panel includes total cholesterol, HDL, LDL, triglycerides (all mmol/L) and total cholesterol:HDL ratio

Outcome measures

Outcome data not reported

Adverse Events

DOR/3TC/TDF

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Sharon Walmsley

University Health Network

Phone: 416-340-5077

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place