HIVPhase 4TLATOANINCT06602622
Change in Body Weight and BMI in PWH with DOR/3TC/TDF Compared with INSTI
A Phase 4 study testing Integrase inhibitor and Doravirine + tenofovir DF + lamivudine in people with HIV and HIV Associate Weight Loss, run by Instituto Mexicano del Seguro Social at 2 sites in Mexico.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years, men only
- Conditions the study is for
- HIV, HIV Associate Weight Loss, HIV-1 Infection
- What is being tested?
- Integrase inhibitor and Doravirine + tenofovir DF + lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 2 sitesMexico
- Study dates
- 14 Aug 2024to 14 Nov 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Virologically suppressed for at least 48 weeks prior to study entry
- 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.
- BMI ≥25 kg/m2 at screening and
- 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.
- Body fat percentage \>20%
- No indication or plans to add or change medications associated with significant weight change during the study period.
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- Participants currently receiving antipsychotics, antidepressants, anticonvulsants/mood stabilizers, and thyroid replacement hormones without dose modifications for at least 12 weeks prior to randomization
- 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).
- Agree to adhere to assigned ART during the study period
- HIV-1 RNA screening \<50 copies/mL performed within 45 days prior to study entry.
- GFR by CDK-EPI ≥60 mL/min
- Alanine aminotransferase (ALT) and asparatate aminotransferase (AST) \< 90 IU/L
- Thyroid profile (TSH, free T3 and free T4) prior to entering the study
- Serum and urinary electrolytes, cystatin C, prior to entering the study
Who cannot join
- Loss of social security
- Allergy to any of the components of ART, previously unknown.
- Withdrawal of informed consent
- Acquiring HBV and/or HCV infection during follow-up.
- HIV-1 RNA \>200 copies/mL in 2 consecutive determinations after having achieved virological suppression.
- 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;
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- 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.
- Planning to undergo or having undergone bariatric surgery.
- Initiating significant dietary changes, advised by a nutritionist according to what was reported by the participant
- Initiating or increasing physical exercise or enrolling in a structured weight loss regimen: \<250 minutes/week of moderate to intense activity
Trial locations and contacts
2 sites in 1 country.
Mexico2 sites, 2 recruiting
- Recruiting
Hospital de infectología, Centro Médico Nacional La Raza
Mexico City, Azcapotzalco, 02990
Ana L Cano, Posgraduated, 522291243665, ana.knodiaz@gmail.com
José A Mata, Doctor, jamatamarin@gmail.com
- Recruiting
Hospital de infectología, Centro Médico Nacional La Raza
Mexico City, Azcapotzalco, 02990
Ana L Cano, Posgraduated, 522291243665, ana.knodiaz@gmail.com
José A Mata, Doctor, 525530379053, jamatamarin@gmail.com
About this study
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
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.
Read the 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;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.
- Conditions
- HIV, HIV Associate Weight Loss, HIV-1 Infection, Integrase Inhibitors, HIV; HIV PROTEASE INHIB, Weight Change, Weight Loss
- Being tested
- Integrase inhibitor, Doravirine + tenofovir DF + lamivudine
- Keywords
- HIV, Integrase inhibitors, doravirine, Body Mass Index, Body Weight Changes
- Medical subject headings
- Body Weight Changes, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Integrase inhibitorDrug
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); 3) DTG 50mg+TDF 300mg/FTC 200mg (DTG+TDF/FTC) Each will be prescribed one tablet every day during 48 weeks
Doravirine + tenofovir DF + lamivudineDrug
Individuals who meet the selection criteria will be randomized to maintain their same regimen with second-generation integrase inhibitors or switch to DOR/TDF/3TC 100/ 300/300 mg It will be prescribed one tablet every day during 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Integrase inhibitors | Active comparator | 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 Receives: Drug: Integrase inhibitor |
| DOR/TDF/3TC | Experimental | 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 Receives: Drug: Doravirine + tenofovir DF + lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in body weight and BMI
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.
Measured: 48 weeks
Secondary outcomes (6)
Adverse events
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
Measured: 48 weeks
Evaluate neuropsychiatric disorders
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.
Measured: 48 weeks
Changes in lipid profile
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.
Measured: 48 weeks
Analyze changes in body composition
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.
Measured: 48 weeks
Cardiovascular risk
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.
Measured: 48 weeks
Kidney function
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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start14 Aug 2024
- Primary completion14 Nov 2025 (estimated)
- Study completion14 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Mexicano del Seguro Social
- Sponsor type
- Other government
- Responsible party
- Principal investigator, José Antonio Mata Marín, Instituto Mexicano del Seguro Social
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06602622
- Sponsor's protocol ID
- R-2024-3502-205
- Acronym
- TLATOANI
- Status last verified
- Sep 2024
- First submitted
- 17 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will be shared if necessary, as it contains personal and sensitive information about participants.
Publications
O'Halloran JA, Sahrmann J, Parra-Rodriguez L, Vo DT, Butler AM, Olsen MA, Powderly WG. Integrase Strand Transfer Inhibitors Are Associated With Incident Diabetes Mellitus in People With Human Immunodeficiency Virus. Clin Infect Dis. 2022 Dec 19;75(12):2060-2065. doi: 10.1093/cid/ciac355.
PubMed 35521785Orkin C, Squires KE, Molina JM, Sax PE, Wong WW, Sussmann O, Kaplan R, Lupinacci L, Rodgers A, Xu X, Lin G, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C, Martin EA; DRIVE-AHEAD Study Group. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis. 2019 Feb 1;68(4):535-544. doi: 10.1093/cid/ciy540.
PubMed 30184165Calza L, Giglia M, Colangeli V, Bon I, Vitale S, Viale P. Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain. HIV Med. 2024 Aug;25(8):919-926. doi: 10.1111/hiv.13644. Epub 2024 Apr 3.
PubMed 38570897Orkin C, Elion R, Thompson M, Rockstroh JK, Alvarez Bognar F, Xu ZJ, Hwang C, Sklar P, Martin EA. Changes in weight and BMI with first-line doravirine-based therapy. AIDS. 2021 Jan 1;35(1):91-99. doi: 10.1097/QAD.0000000000002725.
PubMed 33048879Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Xu X, Rodgers A, Lupinacci L, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C; DRIVE-FORWARD Study Group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018 May;5(5):e211-e220. doi: 10.1016/S2352-3018(18)30021-3. Epub 2018 Mar 25.
PubMed 29592840Bares SH, Wu X, Tassiopoulos K, Lake JE, Koletar SL, Kalayjian R, Erlandson KM. Weight Gain After Antiretroviral Therapy Initiation and Subsequent Risk of Metabolic and Cardiovascular Disease. Clin Infect Dis. 2024 Feb 17;78(2):395-401. doi: 10.1093/cid/ciad545.
PubMed 37698083Sokhela S, Venter WDF, Bosch B, Woods J, McCann K, Akpomiemie G, Chandiwana N, Mashabane N, Tembo A, Simmons B, Lalla-Edward S, Siedner MJ, Sinxadi P, Hermans L, Fairlie L, Vos A, Abrams E, Manne-Goehler JM, Moorhouse M, Clayden P, Norris S, Qavi A, Chersich M, Masenya M, Arulappan N, Hill A. Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens. Open Forum Infect Dis. 2024 Jan 24;11(3):ofae007. doi: 10.1093/ofid/ofae007. eCollection 2024 Mar.
PubMed 38529213Gadde KM, Martin CK, Berthoud HR, Heymsfield SB. Obesity: Pathophysiology and Management. J Am Coll Cardiol. 2018 Jan 2;71(1):69-84. doi: 10.1016/j.jacc.2017.11.011.
PubMed 29301630Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020 Feb;33(1):10-19. doi: 10.1097/QCO.0000000000000616.
PubMed 31789693Hogg RS, Eyawo O, Collins AB, Zhang W, Jabbari S, Hull MW, Lima VD, Ahmed T, Kendall CE, Althoff KN, Justice AC, Barrios R, Shoveller J, Montaner JSG; Comparative Outcomes And Service Utilization Trends (COAST) study. Health-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study. Lancet HIV. 2017 Jun;4(6):e270-e276. doi: 10.1016/S2352-3018(17)30029-2. Epub 2017 Mar 3.
PubMed 28262574Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, Lam JO, Towner WJ, Yuan Q, Horberg MA, Silverberg MJ. Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016. JAMA Netw Open. 2020 Jun 1;3(6):e207954. doi: 10.1001/jamanetworkopen.2020.7954.
PubMed 32539152
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06602622
- Acronym / sponsor ID
- TLATOANI / R-2024-3502-205
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Instituto Mexicano del Seguro SocialOther government
- Study start
- 14 Aug 2024 (actual)
- Primary completion
- 14 Nov 2025 (estimated)
- Study completion
- 14 Nov 2025 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Integrase inhibitors | Active comparator | Drug: Integrase inhibitorSecond 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 | Experimental | Drug: Doravirine + tenofovir DF + lamivudineIndividuals 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Virologically suppressed for at least 48 weeks prior to study entry
- 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.
- BMI ≥25 kg/m2 at screening and
- 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.
- Body fat percentage \>20%
Key exclusion criteria (10 listed)
- Loss of social security
- Allergy to any of the components of ART, previously unknown.
- Withdrawal of informed consent
- Acquiring HBV and/or HCV infection during follow-up.
- HIV-1 RNA \>200 copies/mL in 2 consecutive determinations after having achieved virological suppression.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Integrase inhibitorSecond 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); 3) DTG 50mg+TDF 300mg/FTC 200mg (DTG+TDF/FTC) Each will be prescribed one tablet every day during 48 weeks | Drug | Integrase inhibitors |
| Doravirine + tenofovir DF + lamivudineIndividuals who meet the selection criteria will be randomized to maintain their same regimen with second-generation integrase inhibitors or switch to DOR/TDF/3TC 100/ 300/300 mg It will be prescribed one tablet every day during 48 weeks | Drug | DOR/TDF/3TC |
Primary outcome
Change in body weight and BMI
Time frame: 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.
6 secondary outcomes
Adverse events
Time frame: 48 weeks
Evaluate neuropsychiatric disorders
Time frame: 48 weeks
Changes in lipid profile
Time frame: 48 weeks
Analyze changes in body composition
Time frame: 48 weeks
Cardiovascular risk
Time frame: 48 weeks
Kidney function
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 35521785O'Halloran JA, Sahrmann J, Parra-Rodriguez L, Vo DT, Butler AM, Olsen MA, Powderly WG. Integrase Strand Transfer Inhibitors Are Associated With Incident Diabetes Mellitus in People With Human Immunodeficiency Virus. Clin Infect Dis. 2022 Dec 19;75(12):2060-2065. doi: 10.1093/cid/ciac355.
- Background: PubMed 30184165Orkin C, Squires KE, Molina JM, Sax PE, Wong WW, Sussmann O, Kaplan R, Lupinacci L, Rodgers A, Xu X, Lin G, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C, Martin EA; DRIVE-AHEAD Study Group. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis. 2019 Feb 1;68(4):535-544. doi: 10.1093/cid/ciy540.
- Background: PubMed 38570897Calza L, Giglia M, Colangeli V, Bon I, Vitale S, Viale P. Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain. HIV Med. 2024 Aug;25(8):919-926. doi: 10.1111/hiv.13644. Epub 2024 Apr 3.
- Background: PubMed 33048879Orkin C, Elion R, Thompson M, Rockstroh JK, Alvarez Bognar F, Xu ZJ, Hwang C, Sklar P, Martin EA. Changes in weight and BMI with first-line doravirine-based therapy. AIDS. 2021 Jan 1;35(1):91-99. doi: 10.1097/QAD.0000000000002725.
- Background: PubMed 29592840Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Xu X, Rodgers A, Lupinacci L, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C; DRIVE-FORWARD Study Group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018 May;5(5):e211-e220. doi: 10.1016/S2352-3018(18)30021-3. Epub 2018 Mar 25.
- Background: PubMed 37698083Bares SH, Wu X, Tassiopoulos K, Lake JE, Koletar SL, Kalayjian R, Erlandson KM. Weight Gain After Antiretroviral Therapy Initiation and Subsequent Risk of Metabolic and Cardiovascular Disease. Clin Infect Dis. 2024 Feb 17;78(2):395-401. doi: 10.1093/cid/ciad545.
- Background: PubMed 38529213Sokhela S, Venter WDF, Bosch B, Woods J, McCann K, Akpomiemie G, Chandiwana N, Mashabane N, Tembo A, Simmons B, Lalla-Edward S, Siedner MJ, Sinxadi P, Hermans L, Fairlie L, Vos A, Abrams E, Manne-Goehler JM, Moorhouse M, Clayden P, Norris S, Qavi A, Chersich M, Masenya M, Arulappan N, Hill A. Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens. Open Forum Infect Dis. 2024 Jan 24;11(3):ofae007. doi: 10.1093/ofid/ofae007. eCollection 2024 Mar.
- Background: PubMed 29301630Gadde KM, Martin CK, Berthoud HR, Heymsfield SB. Obesity: Pathophysiology and Management. J Am Coll Cardiol. 2018 Jan 2;71(1):69-84. doi: 10.1016/j.jacc.2017.11.011.
- Background: PubMed 31789693Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020 Feb;33(1):10-19. doi: 10.1097/QCO.0000000000000616.
- Background: PubMed 28262574Hogg RS, Eyawo O, Collins AB, Zhang W, Jabbari S, Hull MW, Lima VD, Ahmed T, Kendall CE, Althoff KN, Justice AC, Barrios R, Shoveller J, Montaner JSG; Comparative Outcomes And Service Utilization Trends (COAST) study. Health-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study. Lancet HIV. 2017 Jun;4(6):e270-e276. doi: 10.1016/S2352-3018(17)30029-2. Epub 2017 Mar 3.
- Background: PubMed 32539152Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, Lam JO, Towner WJ, Yuan Q, Horberg MA, Silverberg MJ. Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016. JAMA Netw Open. 2020 Jun 1;3(6):e207954. doi: 10.1001/jamanetworkopen.2020.7954.
- Individual participant dataSharing planned: No. Individual participant data will be shared if necessary, as it contains personal and sensitive information about participants.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Integrase inhibitor and Doravirine + tenofovir DF + lamivudine in people with HIV and HIV Associate Weight Loss, run by Instituto Mexicano del Seguro Social at 2 sites in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ana L Cano, Postgraduate (2291243665, ana.knodiaz@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in body weight and BMI (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06602622, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.