This research application will explore the impact of the Non-nucleoside reverse transcriptase inhibitor (NNRTI) doravirine in the setting of established Nucleoside reverse transcriptase inhibitors (NRTIs) backbone [Tenofovir alafenamide (TAF) / Emtricitabine (FTC) as a possible therapeutic strategy to minimize the detrimental impact of ART-related toxicities on metabolism and instigators of atherosclerosis. Given the possible favorable role of NNRTI in pathogenesis of HIV-related dyslipidemia and cardiovascular disease (CVD), this research will provide mechanistic insights into HIV pathogenesis and safety data regarding doravirine (DOR). These data may promote DOR as a robust "HDL friendly" and "metabolism friendly", therapeutic agent that may attenuate morbidity in chronic treated HIV infection. Towards this aim, the investigators will study DOR-related effects on HDL (HDL-C levels and function) and ex vivo assays that determine key molecular determinants of atherogenesis.](streamdown:incomplete-link)

Aim 1: To evaluate the relative in vivo impact of DOR on independent measures of HDL function (antioxidant function, cholesterol efflux) compared to integrase inhibitors (raltegravir, dolutegravir, elvitegravir, bictegravir) in the setting of TAF backbone in HIV infected persons with dyslipidemia.

Aim 2: To evaluate the relative in vivo impact of DOR on ex vivo atherogenesis (monocyte-derived foam cell efflux and chemotaxis) compared to integrase inhibitors (raltegravir, dolutegravir, elvitegravir, bictegravir) in the setting of TAF backbone.

Inclusion Criteria:

• 18 years of age or older
• Cases: Chronically infected and on anti-retroviral therapy with suppressed viremia for at least 3 months (viral RNA <50 copies per ml)
• On stable antiretroviral therapy for >6 months with Genvoya (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg; E/C/F/TAF) 2) Biktarvy (bictegravir 50 mg/ emtricitabine 200 mg/tenofovir alafenamide 25 mg; B/F/TAF).
• Dyslipidemia (Defined based on use of lipid lowering medications or abnormal baseline lipids (total cholesterol, triglycerides, high density lipoprotein): Rationale: Enrolling participants with dyslipidemia will determine whether switching from TAF/FTC/integrase inhibitor regimen to TAF/FTC/doravirine regimen will directly improve the lipids over 3 months within the same participant.
• Adequate renal function determined by the Cockcroft-Gault formula for creatinine clearance (>60 mL/min/1.73 m2
• Able and willing to provide written consent

Exclusion Criteria:

• • Pregnancy

  • Hepatitis; no evidence of acute hepatitis in the prior 30 days
  • History of severe renal impairment (eGFR < 30 ml/min/1.73 m2)
  • History of severe or recent cardiac event
  • Current alcoholism or IV drug abuse
  • Use of systemic immunomodulatory medications (e.g. steroids) within 4 weeks of enrollment
  • Anemia precluding safe donation of blood (For men, anemia is typically defined as hemoglobin level of less than 13.5 gram/100 ml and in women as hemoglobin of less than 12.0 gram/100 ml).
  • Use of any investigational products within 4 weeks of enrollment
  • Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease.
  • Subjects who are on medications that are strong inducers of CYP3A (as these may decrease the efficacy of Stribild or Genvoya). Examples include phenobarbital, phenytoin, carbamazepine, and rifampin.
  • Subjects who are on medications that are cleared by CYP3A and that may be toxic with elevated drug levels (examples include Cisapride, ergotamine, Pimozide, Lurasidone, Lovastatin, and Simvastatin).