Status:
COMPLETED
Explorations Into the Mechanism for INSTI-associated Weight Gain: a Focus on Energy Balance
Lead Sponsor:
University of Colorado, Denver
Collaborating Sponsors:
Gilead Sciences
Conditions:
HIV-1-infection
Weight Gain
Eligibility:
All Genders
18+ years
Brief Summary
Weight gain following antiretroviral therapy (ART) initiation occurs with all modern regimens. Recent real-world reports suggest that integrase strand transfer inhibitor (INSTI)-based ART may be assoc...
Eligibility Criteria
Inclusion
- Adults age \>=18 years
- BMI of \>=30.0 kg/m2
- \>=10% weight gain within the first 2 years of switching to INSTI-based ART (bictegravir or dolutegravir-based regimens only), with weight gain that has continued or worsened (not decreased).
- At least one plasma HIV-1 RNA \<50 copies/mL while on the current INSTI-based ART within 6 months of screening
- Willing to switch to doravirine and pay any associated co-pays that may not be covered by insurance.
- NRTI back-bone therapy with either TAF or TDF with 3TC or FTC and willing to continue these 2 agents
Exclusion
- Use of an INSTI other than bictegravir or dolutegravir within the 1 year prior to entry
- Any plasma HIV-1 RNA \>500 copies/mL within one year prior to entry
- Pregnant, breast-feeding, or intention to become pregnant during the study period.
- Participants using medications with a potential serious drug-drug interaction with doravirine that cannot be attenuated through dose change will also be excluded.
- Any plans to change diet or exercise regimen significantly within the study period.
- NOTE: Significantly refers to intent to join a weight-loss program such as Weight Watchers, start a specific diet (such as ketogenic or very low carbohydrate).
- \- Use of human growth hormone, tesamorelin, supra-physiologic testosterone to achieve therapeutic blood levels, or any use of other anabolic steroids within 3 months prior to study entry or plans to start these on study.
- NOTE: Chronic, stable hormone replacement therapy ≥3 months prior to entry in men with diagnosed hypogonadism or transgender person on masculinizing hormonal therapy is permitted.
- \- Use of estrogens or progesterones at supraphysiologic doses within 3 months prior to study entry.
- NOTE: Stable doses used for contraception, post-menopausal hormone replacement or feminizing hormone therapy for transgender persons ≥3 months prior to entry is permitted.
- Use of prednisone (or equivalent steroid) within the prior 3 months, unless stable dosing ≤ 10mg
- Change or initiation of lipid- and/or glucose-lowering therapy in the 12 weeks prior to entry, or planned need for such therapy during the study period. Use of stable lipid- and/or glucose-lowering therapy during the study is allowed.
- Current serious illness requiring systemic treatment and/or hospitalization until participant completes therapy or is clinically stable as determined by the site investigator.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Intent to use any medication likely to cause significant changes in weight during the study period.
- NOTE: A list of medications in this category will be provided.
- Prior bariatric surgery (e.g., lap band, gastric sleeve, or roux-en-y bypass surgery) or major gastric surgery or plans to undergo weight reduction surgery while on study.
- Screening laboratory values as follows:
- ANC \< 500 cells/mm3 Hemoglobin \< 9 gm/dL Cr Cl \< 30 mL/min (estimated by CKD-Epi equation) Fasting blood sugar \<200
- Any chronic, end-stage organ disease that would impact metabolism, including end-stage liver or renal disease, cardiac cachexia, chronic obstructive pulmonary disease, or cancer
- Any condition that the study investigator believes would make the candidate unsuitable for participation.
- Severe claustrophobia that would limit ability of participant to remain in the whole room calorimeter
- Known resistance to any component of the study drugs, including detection of any of the following resistance mutations on prior HIV genotype test (genotype testing not required if not available): Doravirine resistance: V106A, V106I, V106T, V106M, Y188C, Y188H, Y188L, G190E, P225H, F227C, F227L, F227R, M230L, L234I Resistance to NRTIs: K65R, K65E, K65N, T69S (insertion complex), K70E, L74V, Y115F, Q151M, M184I, M184V.
- Active severe depression or anxiety, as evidenced by recent inpatient psychiatric admission (within the prior 6 months); PHQ-2 score of 6 (response of 'nearly every day' to 'do you have little interest or pleasure in doing things' or 'feeling down, depressed, or hopeless'; expressed suicidal ideations.
- Under the care of a provider for disordered eating (bulimia, anorexia, or other).
- Diabetes will be permitted if well-controlled with a Hb A1C of 7.5% of less in the prior 6 months and no use of insulin.
- Routine physical activity meeting or exceeding 150 minutes/week of moderate or vigorous activity, for at least 3 months prior to the study
Key Trial Info
Start Date :
October 22 2020
Trial Type :
OBSERVATIONAL
Allocation :
ACTUAL
End Date :
June 5 2023
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT04495348
Start Date
October 22 2020
End Date
June 5 2023
Last Update
June 22 2023
Active Locations (2)
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1
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States, 80045
2
UTHealth
Houston, Texas, United States, 77030