Overview
Background:Historically, HIV infection was associated with significant weight loss. However, weight gain is now commonly observed after initiating antiretroviral therapy (ART), particularly in individuals underweight at baseline. It remains unclear whether this weight gain reflects a "return to health" or results from drug-related or metabolic effects, and whether it persists beyond immune restoration. Recent evidence indicates that ART regimens containing second-generation integrase strand transfer inhibitors (INSTIs), such as bictegravir combined with tenofovir alafenamide, are associated with greater weight gain compared to other antiretroviral combinations, raising concerns about potential long-term metabolic consequences.Objective:To evaluate the effectiveness, safety, and tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) compared with Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) in ART-naïve people living with HIV (PWH) who are overweight or obese.Materials and Methods:This open-label, randomized clinical trial, approved by the Ethics and Scientific Research Committee (No. 3502), will be conducted at the Infectious Diseases Hospital of the National Medical Center "La Raza" from May 2025 to May 2027. ART-naïve PWH, recently diagnosed, with no prior use of pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), who do not require hospitalization, and have a body mass index (BMI) ≥25 kg/m² and body fat >20%, will be invited to participate. Participants will provide written informed consent and be randomized 1:1 to receive either DOR/3TC/TDF or BIC/FTC/TAF.
Description
Study Assessments Measurements: Laboratory tests, vital signs, and body composition (via bioimpedance) will be assessed at weeks 4, 12, 24, 36, 48, 72, 96, 120, and 144. HIV viral load and CD4+ count will be measured at weeks 12, 24, 48, 72, 96, 120, and 144.Statistical Methods: Non-probabilistic sampling will be used. Data distribution will be evaluated with the Kolmogorov-Smirnov test. Descriptive statistics (means, medians, percentages) will be reported. Between-group comparisons will use the Mann-Whitney U test for continuous variables and chi-square or Fisher's exact test for categorical variables. Longitudinal analysis at weeks 12, 24, 48, 96, and 144 will employ the Wilcoxon test. A p-value ≤0.05 with a 95% confidence interval will indicate statistical significance.Study ProcedureEligible ART-naïve PWH attending the HIV clinic will be identified and invited to participate. After providing informed consent, participants will be informed that participation is voluntary and can be withdrawn at any time without consequences.
Baseline Visit
- Data Collection: A medical interview will gather sociodemographic, clinical, and comorbidity data, as well as lifestyle habits (diet, physical activity, alcohol use, smoking).
- Anthropometric Measurements: Conducted using a 4-point segmental bioimpedance scale (FitScan Segmental Body Composition Monitor C-545F) to assess weight, water percentage, muscle mass, bone mass, and fat percentage. Waist and hip circumference, blood pressure, heart rate, respiratory rate, and oxygen saturation will also be measured.
- Laboratory Assessments: Include glucose, creatinine, cystatin C, serum and urinary electrolytes, lipid profile, liver function tests, elastography (visceral and subcutaneous fat), complete blood count, HIV viral load, CD4+ count, hepatitis B and C serologies, and VDRL.
Randomization and Follow-Up Participants will be randomized using the MEDSHARING digital system to either DOR/3TC/TDF or BIC/FTC/TAF. Follow-up visits will occur at specified intervals through week 144. Adverse events will be monitored using the DAIDS grading scale. Neuropsychiatric assessments will use the Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), and Patient Health Questionnaire (PHQ-9). Treatment satisfaction and distress will be evaluated with the HIV Treatment Satisfaction Questionnaire (HIVTSQ) and HIV Symptom Distress Module (HIVSDM).
Sampling and Sample Size
Simple random sampling will be employed. The sample size is 306 participants per group, calculated based on:
- 80% statistical power
- Alpha level of 0.05
- 12% non-inferiority margin
- 80% expected virologic response at week 48
- 10% attrition rate Statistical Analysis
- Categorical Variables: Reported as frequencies and percentages.
- Continuous Variables: Described using means ± standard deviations or medians with interquartile ranges.
- Statistical Tests:
- Between-group comparisons: Mann-Whitney U or Student's t-test
- Within-group comparisons: Wilcoxon or paired t-test
- Multiple time points: Friedman or repeated-measures ANOVA
- Associations: Chi-square or Fisher's exact test
- Multivariate analysis: Binary logistic regression
- Software: SPSS v29.0.2 for Mac (IBM) will be used for data analysis. Ethical Considerations and Data Confidentiality The study adheres to the Declaration of Helsinki, CIOMS/WHO, and ICH-GCP guidelines. Approval has been obtained from the institutional Ethics and Research Committee. Participant confidentiality will comply with IMSS policy and Mexican regulations, using anonymized unique codes. Only standard-of-care treatments per national and international guidelines will be used. Risks are minimal, primarily related to venipuncture, with medical evaluation and treatment provided as needed
Eligibility
Inclusion Criteria:
- Adults (≥18 years) with confirmed HIV diagnosis, ART-naïve
- Signed informed consent
- HIV-1 RNA ≥1000 copies/mL
- No history of PrEP or PEP failure
- BMI ≥25 kg/m² and body fat >20%
- Stable treatment for dyslipidemia (if applicable)
- No planned medication changes affecting weight
- Willingness to adhere to assigned ART
- Recent HIV-1 RNA and CD4+ results
- GFR (CKD-EPItip) ≥60 mL/min
- ALT and AST <90 IU/L
- Willingness to report dietary or physical activity changes during follow-up Non-Inclusion Criteria
- Uncontrolled diabetes 2. Recent changes in insulin or hypoglycemic drugs (<3 months)
- Active malignancy 4. History of bariatric surgery 5. Allergies to study drugs 6. Hepatitis B and/or C coinfection 7. GFR <60 mL/min (CKD-EPI) 8. Drug interactions with ART regimens 9. Recent (60 days) use of anorectic drugs 10. Recent (30 days) hospitalization for severe illness 11. Unstable hypothyroidism
Exclusion Criteria:
- Loss of social security coverage
- Newly discovered allergy to study drugs
- Withdrawal of consent
- Hepatitis B or C infection acquired during follow-up
- Use of psychiatric or thyroid medications without a stable dose for ≥12 weeks
- Initiation or discontinuation of medications affecting weight after enrollment
- Unplanned bariatric surgery