Can INSTI-associated Weight Gain be Halted or Reversed With a Switch to Doravirine/Lamivudine/Tenofovir DF?

• Status: Enrolling by invitation
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Weight gain with the integrase inhibitors and tenofovir alafenamide has been observed in observational cohorts and randomized controlled clinical trials. Although some risk factors have been identified, the cause is unknown and it remains to be determined if the changes are reversible. The weight gain is of concern to persons living with HIV. This pilot intervention study is designed to provide preliminary data on whether switching patients with weight gain on an INSTI-based regimen to a combination of doravirine/tenofovir disoproxil fumarate/lamivudine (DOR/3TC/TDF, an NNRTI-based regimen) for one year can slow down or even reverse weight gain. These data will then be used to inform the design and sample size of a larger switch study.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Health Network, Toronto
• Collaborator: Merck Canada Inc.

Criteria

Inclusion Criteria:

• Documented HIV-1 infection by means of any one of the following:

Documentation of HIV diagnosis in the medical record by a licensed health care provider; OR HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating >1000 RNA copies/mL; OR any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid Multispot antibody differentiation assay.

• On an Integrase Strand Transfer Inhibitor (INSTI) based regimen for at least 1 year and less than 5 years prior to screening

• Significant weight gain since initiation of the INSTI-based regimen (>10% of baseline body weight)

• Viral load of <200 copies/mL for > 6 consecutive months prior to screening (single viral blips <200 copies/mL accepted if re-suppressed)

• Documentation of weight, glycemia, cholesterol, and blood pressure (BP) history within the last year.

• Signed Informed Consent Form (Appendix B) and willing to comply with the protocol.

• Using proper contraception if of child bearing age and potential.

Exclusion Criteria:

• Pregnancy or desire to become pregnant within the next year

• Failure to use adequate contraception during the study if of child-bearing potential.

• Any underlying documented ART resistance to doravirine, tenofovir disoproxil fumarate, or lamivudine

• Prior virologic failure

• Concomitant drugs that interact with doravirine

• Initiated on concomitant drugs known to cause weight gain within the last 6 months (i.e. antidepressants and antipsychotics)

• Concomitant drugs known to cause nephrotoxicity

• History of renal toxicity or renal events while on TDF therapy.

• Creatinine clearance (CrCL) < 50 mL/min

• Inability to read/understand English