Change in Body Weight and BMI in PWH with DOR/3TC/TDF Compared with INSTI

Phase 4

Recruiting

• Conditions: HIV; HIV Associate Weight Loss; HIV-1 Infection; Integrase Inhibitors, HIV; HIV PROTEASE INHIB; Weight Change; Weight Loss
• Interventions: Drug: Integrase inhibitor; Drug: Doravirine + tenofovir DF + lamivudine

• Registration Number: NCT06602622
• Lead Sponsor: Instituto Mexicano del Seguro Social

Brief Summary

Patients who developed metabolic syndrome after initiation of HIV treatment or with antiretroviral therapy (ART) for at least 36 months, treated with second generation integrase inhibitors (BIC/TAF/FTC, DTG/ABC/3Tc or DTG+TDF/FTC) who have gained at least 10% of their total body weight after starting ART, with a body mass index ≥25 kg/m2 and body fat greater than 20% will be eligible to participate in this clinical trial. If they decide to participate, they will sign an informed consent. After this, a mobile application will randomly decide whether the participant will continue with their ART regimen or switch to another ART (listed in the guidelines as one of the main lines of treatment) containing doravirine/lamivudine/disoproxil fumarate tenofovir. Medical visits will be at 1 month, 3 months, 6 months, 9 months, and 12 months after get in to this protocol, with laboratory studies that evaluate fats, blood sugar, liver function, kidney function, and test for HIV control; in addition, each visit will be given self-fillable scales to evaluate neuropsychiatric disorders such as depression, anxiety, insomnia, satisfaction with treatment or symptoms associated with it.The aim of the study is to observe whether there is weight loss with the change in HIV treatment.

Detailed Description

Open-label, randomized clinical trial, conducted at the infectious disease hospital, La Raza National Medical Center, Mexico City, from July 2024 to November 2025.

The aim of the study is to determine the percentage change in body weight and BMI in virologically suppressed PWH maintaining a second-generation INSTI (BIC/TAF/FTC, DTG/ABC/3TC or DTG+TDF/FTC) regimen compared with those switching to DOR/3TC/TDF at 48 weeks post-switch.

PWH who are on a second-generation INSTI regimen who are virologically suppressed (HIV-1 RNA minor to 50 copies/mL) and have gained ≥10% of their body weight compared to their weight before starting ART, BMI ≥25 kg/m2, and body fat greater than 20% will be identified, and invited to participate.

A medical interview will be conducted to assess clinical characteristics, comorbidities of the study subject, new drugs, changes in doses or suspensions, as well as plans by their other physicians for changes in the same, diet, frequency and intensity of exercise. Once the preliminary information has been obtained, it will be established whether the patient is a candidate to take part in the study and will be invited to participate voluntarily. The project and the probable results, benefits and risks of participating will be explained in detail and in detail; If they agree to participate, informed consent will be obtained from the principal investigator or associate researchers during the medical visit where weight gain and BMI are identified, for authorization to take clinical exams, anthropometric measurements (these will be carried out by the principal investigator or associates). A response will be obtained during the same medical visit with free decision to continue or withdraw from the study at the time deemed appropriate during the study period without this affecting your medical care at the HIV clinic. (Annex 1) Patients who accept will be asked again for HIV-1 RNA, CD4+, complete blood count, lipid profile, complete liver enzymes, cystatin C and urinary electrolytes within 45 days prior to randomization, and if they meet the inclusion criteria, through simple randomization and with the randomizer for clinical trial application, the principal investigator will randomize them into the group of maintaining the previous regimen with second-generation INSTI or changing the regimen to DOR/3TC/TDF, and in order to maintain privacy, a folio number will be assigned at the time of recruitment.

Weight measurements will be taken with a FitScan segmental body composition monitor BC-545F scale, height in centimeters, body mass index (BMI) with the formula weight (kg)/height (m2), body composition (fat in %, water in %, muscle in kg, bone in kg) with a FitScan segmental body composition monitor BC-545F equipment, waist and hip measurements with a measuring tape in cm.

Laboratory studies will include complete blood count, complete blood chemistry with glucose, creatinine, complete lipid profile, and liver function tests after randomization at 4 weeks, 12 weeks, 24 weeks, and 48 weeks post-switch. CD4+, HIV-1 RNA, Cystatin C, and urinary electrolytes will be determined prior to randomization, at 6 months, and 12 months after entering the study. Comparisons will be made between measurements taken prior to entering the study, at 24 and 48 weeks after entering the study.

In case of elevated AST and/or ALT \>90 IU/L, serologies will be requested to rule out HBV and HCV.

The PSQI, ISI, HADS-A, and HADS-D questionnaires will be used to assess anxiety, depression, and sleep quality; in addition, the HIVTSQ questionnaire will be used to assess treatment satisfaction at weeks 4, 12, 24, and 48 weeks after randomization, and HIV Symptoms Distress Module (HIV-SDM).

The change in weight and BMI at 48 weeks will be defined as the difference between the weight and BMI prior to randomization compared to the results at 48 weeks, weight will be expressed in kg, percentages and BMI in kg/m2.

The sampling was simple random, participation in the study was offered to all Mexican patients living with HIV who have gained ≥10% of body weight and BMI ≥25% from a regimen with second-generation integrase inhibitor (BIC/TAF/FTC or DTG/ABC/3TC).

Sample size per group: 54 participants per group. Calculated based on the expected change after switching from INSTI to a regimen with DOR/TDF/3TC, with estimated losses of 20%, 108 participants in total.

Kolmogorov-Smirnoff test will be used to identify distribution of data and to express central tendency measures (medians with interquartile ranges) and percentages accordingly. Data will be compared using the Mann-Whitney U test. Qualitative data will be analyzed using the x2 or Fisher´s exact test, as appropriate. Subsequently, data will be analyzed by groups at 12, 24, 36, and 48 weeks using the Wilcoxon test. A P value ≤0.05 with a 95% confidence interval will be considered statistically significant.

Study Timeline

• Study Start: 2024-08-14
• Status Verified: 2024-09
• Study First Submitted: 2024-09-17
• Study First Submitted QC: 2024-09-17
• Last Update Submitted: 2024-09-17
• Study First Posted: 2024-09-19
• Last Update Posted: 2024-09-19
• Primary Completion: 2025-11-14
• Study Completion: 2025-11-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 108

Inclusion Criteria

1. Virologically suppressed for at least 48 weeks prior to study entry
2. Coming from a regimen containing Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF), Dolutegravir/Lamivudine/Abacavir (DTG/3TC/ABC), or, Dolutegravir/Tenofovir Disoproxil Fumarate/Emtricitabine (DTG+TDF/FTC) with no known failures to integrase inhibitors for al least 48 weeks.
3. BMI ≥25 kg/m2 at screening and
4. Unintentional weight gain of >10% from baseline (prior to INSTI initiation) within 1-3 years of starting INSTI ART, with no other apparent medical reason to explain the weight gain (concomitant medication use, Cushing's disease, recent prolonged hospitalization, etc.), in the opinion of the site investigator.
5. Body fat percentage >20%
6. No indication or plans to add or change medications associated with significant weight change during the study period.
7. Participants currently receiving antipsychotics, antidepressants, anticonvulsants/mood stabilizers, and thyroid replacement hormones without dose modifications for at least 12 weeks prior to randomization
8. Participants currently receiving antidiabetics known to cause weight loss and without dose modifications for at least 24 weeks prior to randomization (GLP-1 receptor agonists, SGLT-2 inhibitors, insulin, metformin).
9. Agree to adhere to assigned ART during the study period
10. HIV-1 RNA screening <50 copies/mL performed within 45 days prior to study entry.
11. GFR by CDK-EPI ≥60 mL/min
12. Alanine aminotransferase (ALT) and asparatate aminotransferase (AST) < 90 IU/L
13. Thyroid profile (TSH, free T3 and free T4) prior to entering the study
14. Serum and urinary electrolytes, cystatin C, prior to entering the study

Exclusion Criteria

1. Loss of social security
2. Allergy to any of the components of ART, previously unknown.
3. Withdrawal of informed consent
4. Acquiring HBV and/or HCV infection during follow-up.
5. HIV-1 RNA >200 copies/mL in 2 consecutive determinations after having achieved virological suppression.
6. Early initiation or discontinuation of any of the following drugs after entering the study: antipsychotics (clozapine, olanzapine, risperidone); antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors) monoamine oxidase inhibitors, associated with weight gain; anticonvulsants/mood stabilizers (lithium, valproic acid) or associated with weight loss (topiramate); thyroid replacement hormones;
7. Change in dose or discontinuation of antidiabetic drugs that cause weight loss (GLP-1 receptor agonists, SGLT-2 inhibitors, insulin, metformin), after entering the study.
8. Planning to undergo or having undergone bariatric surgery.
9. Initiating significant dietary changes, advised by a nutritionist according to what was reported by the participant
10. Initiating or increasing physical exercise or enrolling in a structured weight loss regimen: <250 minutes/week of moderate to intense activity

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Integrase inhibitors	Integrase inhibitor	Second generation integrase inhibitor: 1) Bictegravir 50 mg/ alafenamide tenofovir 25 mg/ emtricitabine 200 mg (BIC/TAF/FTC) 2) Dolutegravir 50 mg/ abacavir 600 mg/ lamivudine 300 mg (DTG/ABC/3TC) or ) dolutegravir 50 mg+ disoproxil fumarate tenofovir/ emtricitabine 300mg/ 200 mg (DTG+TDF/FTC) Each will be prescribed one tablet every day during 48 weeks
DOR/TDF/3TC	Doravirine + tenofovir DF + lamivudine	Individuals who meet the selection criteria will be randomized to maintain their same regimen with second-generation integrase inhibitors or switch to Doravirine/Tenofovir Disoproxil Fumarate/Emtricitabine 100/300/300 mg (DOR/TDF/3TC) It will be prescribed one tablet every day during 48 weeks

Primary Outcome Measures

Name	Time	Method
Change in body weight and BMI	48 weeks	To determine the percentage change in body weight and BMI in virologically suppressed PLHIV maintaining a second-generation INSTI regimen compared with those switching to DOR/3TC/TDF at 48 weeks post-switch. This will be measured with with the same scale at baseline, 1 month, 3 months, 6 months, 9 months and 12 months.

Secondary Outcome Measures

Name	Time	Method
Adverse events	48 weeks	Evaluate the number and degree of adverse events in each group of ART at baseline, 1 month, 3 months, 6 months, 9 months and 12 months post-recruitment
Evaluate neuropsychiatric disorders	48 weeks	Assess sleep quality using the Insomnia Severity Score (ISI) baseline and at 48 weeks Assess anxiety and depression using the Hospital Anxiety and Depression Scales (HADS-A and HADS-D) baseline and at 48 weeks Assess the presence and degree of depression using the Patient Health Questionnaire-9 (PHQ-9) baseline and at 48 weeks. This will be measured at baseline, 1 month, 3 months, 6 months, 9 months and 12 months.
Changes in lipid profile	48 weeks	Analyze changes in total cholesterol, hdl cholesterol and triglycerides at baseline and 48 weeks after switch. This will be evaluated at baseline, 1 month, 3 months, 6 months, 9 months and 12 months.
Analyze changes in body composition	48 weeks	Fat in percentage, muscle in kilograms, water in percentage and bone in kilograms. This will be evaluated with same bioimpedance equipment at baseline, 1 month, 3 months, 6 months, 9 months and 12 months.
Cardiovascular risk	48 weeks	Determine cardiovascular risk using Framingham scale and Atherosclerotic Cardiovascular Disease. (ASCVD) at baseline an 48 weeks. This will be evaluated at baseline, 6 months, and 12 months.
Kidney function	48 weeks	Analyze changes in renal function using creatinine, cystatin C, and urinary electrolytes at baselina and 48 weeks. This will be evaluated at baseline, 6 months, and 12 months.

Trial Locations

Locations (1)

Hospital de infectología, Centro Médico Nacional La Raza; 🇲🇽 Mexico city, Azcapotzalco, Mexico