Explorations Into the Mechanism for INSTI-associated Weight Gain: a Focus on Energy Balance

Inclusion Criteria: * 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 Criteria: * 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