Melanocortin-4 Receptor Gene Variants and Weight Change Following Switch to Integrase Inhibitor-Based Antiretroviral Therapy
Given the melanocortin-4 receptor's (MC4R) importance in obesity, we examined associations between <i>MC4R</i> gene variants and weight following a switch to integrase inhibitor-containing antiretroviral therapy among participants in Advancing Clinical Therapeutics Globally studies. Among 529 persons with HIV (median age: 50 years, 29% non-Hispanic Black, 22% female), 62% were overweight or obese at integrase strand transfer inhibitor switch, and 62% switched to raltegravir. In adjusted linear models, three variants were associated (<i>P</i> < .05) with weight change after switch in all participants or in prespecified subgroups. These exploratory findings are consistent with the role of melanocortins in appetite and weight and suggest a neuroendocrine contribution to integrase inhibitor-related weight gain.
Authors
- Grace A. McComsey (ORCID: https://orcid.org/0000-0003-2690-8888)
- Paul E. Sax (ORCID: https://orcid.org/0000-0001-8434-174X)
- Kristine Mace Erlandson (ORCID: https://orcid.org/0000-0003-0808-6729)
- David W. Haas (ORCID: https://orcid.org/0000-0002-5813-1594)
- Todd Hulgan (ORCID: https://orcid.org/0000-0002-3339-067X)
- Jordan E. Lake (ORCID: https://orcid.org/0000-0002-0640-5514)
- Michael Leonard
- Todd T. Brown (ORCID: https://orcid.org/0000-0001-8599-278X)
- Sara Hurtado Bares (ORCID: https://orcid.org/0000-0002-2130-2505)
- Marylyn DeRiggi Ritchie (ORCID: https://orcid.org/0000-0002-1208-1720)
- John R. Koethe (ORCID: https://orcid.org/0000-0001-6490-6942)
- Kunling Wu
- Katherine Tassiopoulos (ORCID: https://orcid.org/0000-0003-4773-2535)
- Yuki Bradford
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Case Western Reserve University (US)
- University of Nebraska Medical Center (US)
- University of Pennsylvania (US)
- Vanderbilt University Medical Center (US)
- The University of Texas Health Science Center at Houston (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Open Forum Infectious Diseases
- Published
- 2025-11-22
- DOI
- https://doi.org/10.1093/ofid/ofaf696
- Primary Topic
- Regulation of Appetite and Obesity
- Type
- article
- Field-Weighted Citation Impact
- 0.00