Swiss HIV Cohort StudySchwenke, Johannes M.Thorball, Christian W.Schoepf, Isabella C.Ryom, LeneHasse, BarbaraLamy, OlivierCalmy, AlexandraWandeler, GillesMarzolini, CatiaKahlert, Christian R.Bernasconi, EnosKouyos, Roger D.Gunthard, Huldrych F.Ledergerber, BrunoFellay, JacquesBurkhalter, FelixTarr, Philip E.2023-07-172023-07-172023-07-172023-05-2410.1093/infdis/jiad179https://infoscience.epfl.ch/handle/20.500.14299/199258WOS:001021908600001An individual polygenic risk score was associated with osteoporosis in people living with HIV. The genetic effect was robust, as it persisted after multivariable adjustment for established traditional and HIV-related osteoporosis risk factors, including tenofovir disoproxil fumarate and boosted protease inhibitor exposure.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 & GE;2 per-protocol dual x-ray absorptiometry (DXA) measurements & GE;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.ImmunologyInfectious DiseasesMicrobiologyaginghiv infectionlow bone mineral densityosteoporosispolygenic risk scorebone-mineral densitysingle-nucleotide polymorphismsgenetic-determinantsinfected patientsmassheritabilitymetaanalysisindividualshepatitistenofovirtext::journal::journal article::research article