Background: Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH.
Methods: Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011-2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements.
Results: We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9).
Conclusions: In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.
Competing Interests: Potential conflicts of interest. P. E. T.’s institution reports grants and other fees from Gilead, Merck, and ViiV, outside the submitted work. A. C. has received unrestricted educational and research grants from MSD, Gilead, and ViiV. B. L. received personal fees from Kantonsspital Baselland, Liestal, Switzerland, during the conduct of the study and reports personal fees from Gilead and ViiV, outside the submitted work. C. M. has received speaker honoraria from ViiV, MSD, and Pfizer unrelated to this work. E. B.’s institution reports fees for advisory board participation from Gilead Sciences, ViiV Healthcare, MSD, Pfizer, Astra Zeneca, and Ely Lilly and travel grants from Gilead Sciences, ViiV Healthcare, MSD, and Abbvie, outside the submitted work. H. F. G. reports honoraria from Gilead Sciences, Merck, ViiV, GSK, Janssen, Johnson and Johnson, and Novartis for serving on data and safety monitoring and/or advisory boards and has received a travel grant from Gilead Sciences. In addition, he has received grants from the Yvonne Jacob Foundation and unrestricted research grants from Gilead Sciences, all paid to the institution. G. W. reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and Abbvie and an unrestricted research grant from Gilead Sciences; all remuneration was provided outside the submitted work. I. C. S.'s institution received a lecture fee from ViiV, outside the submitted work. R. D. K. has received personal fees from Gilead Sciences, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)