Clinical trial NCT06602622: Change in Body Weight and BMI in PWH with DOR/3TC/TDF Compared with INSTI
Official title: Change in Body Weight and BMI in PWH Virologically Suppressed Who Maintain a Second-generation INSTI Regimen Compared to Those Who Switch to DOR/3TC/TDF At 48 Weeks
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: HIV
HIV Associate Weight Loss
HIV-1 Infection
Integrase Inhibitors, HIV; HIV PROTEASE INHIB
Weight Change
Weight Loss
Keywords: HIV
Integrase inhibitors
doravirine
Body Mass Index
Body Weight Changes
Lead sponsor: Instituto Mexicano del Seguro Social
Sponsor class: OTHER_GOV
First posted: 2024-09-19
Enrollment: 108
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label, randomized, clinical trial. Individuals who meet the inclusion criteria will be randomized to maintain their integrase inhibitor regimen (BIC/TAF/FTC, DTG/ABC/3TC or DTG+TDF/FTC) or to DOR/TDF/3TC.
Primary purpose: TREATMENT

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 \&amp;amp;amp;amp;gt;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.

Eligibility criteria: 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 \&gt;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 \&gt;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 \&lt;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) \&lt; 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 \&gt;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: \&lt;250 minutes/week of moderate to intense activity

Primary outcomes:
measure: Change in body weight and BMI
timeFrame: 48 weeks
Secondary outcomes:
measure: Adverse events
timeFrame: 48 weeks
measure: Evaluate neuropsychiatric disorders
timeFrame: 48 weeks
measure: Changes in lipid profile
timeFrame: 48 weeks
measure: Analyze changes in body composition
timeFrame: 48 weeks
measure: Cardiovascular risk
timeFrame: 48 weeks
measure: Kidney function
timeFrame: 48 weeks
Other outcomes:
measure: HIVSDM scale symptom distress scale
timeFrame: 48 weeks
measure: HIV Treatment Satisfaction Questionnaire (HIVTSQ)
timeFrame: 48 weeks
Locations:
city: Mexico city
country: Mexico
facility: Hospital de infectología, Centro Médico Nacional La Raza
state: Azcapotzalco
city: Mexico city
country: Mexico
facility: Hospital de infectología, Centro Médico Nacional La Raza
state: Azcapotzalco
Study officials:
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