Evaluation of bone mineral density of individuals living with HIV followed at Marmara University Pendik Training and Research Hospital

Abstract

With the effective use of antiretroviral therapies (ART), the life expectancy of individuals living with Human Immunodeficiency Virus (HIV) is increasing. The negative effects of both advancing age, HIV, and ART on bone health are becoming a current issue. HIV-infected men aged ≥18 years, men aged ≥50 years, postmenopausal women, and women aged <40 years who have entered menopause who were followed up in our clinic between January 1, 2013 and May 1, 2024 were included in this study. Their bone mineral density (BMD) results, ARTs they were using, and duration were screened. The conformity of the data to normal distribution of the data was assessed using the Shapiro-Wilk test, and Mann-Whitney U, Kruskal-Wallis, Chi-square, and Wilcoxon signed-rank tests were used for inter- and intra-group comparisons. Of the 263 HIV-infected individuals who met the criteria, 220 had at least one BMD measurement. BMD was evaluated as normal in 116 (52%), osteopenic in 84 (38%), and osteoporotic in 20 (9%) individuals. While the average duration of tenofovir alafenamide (TAF) use in those with normal BMD was 10 months, the average duration of tenofovir disoproxil fumarate (TDF) use was 39 months. The average duration of TAF and TDF use in those with osteopenia/osteoporosis was found to be 8 and 32 months, respectively. We found that 48% of individuals living with HIV who had at least one BMD measurement had osteopenia or osteoporosis. This situation highlights the importance of following the recommendations of the guidelines in BMD screening.

Keywords

• Human immunodeficiency virus
• HIV
• Bone mineral density
• Osteopenia
• Osteoporosis

MARMARA ÜNİVERSİTESİ PENDİK EĞİTİM VE ARAŞTIRMA HASTANESİ’NDE TAKİP EDİLEN HIV İLE YAŞAYAN BİREYLERİN KEMİK MİNERAL YOĞUNLUKLARININ DEĞERLENDİRİLMESİ

Abstract

Antiretroviral tedavilerin (ART) etkin şekilde kullanılmasıyla Human Immunodeficiency Virus (HIV) ile yaşayan bireylerin yaşam süreleri uzamaktadır. Hem ilerleyen yaş hem HIV hem de ART’lerin kemik sağlığı üzerine olumsuz etkileri gündeme gelmektedir. Bu çalışmada 1 Ocak 2013 ile 1 Mayıs 2024 tarihleri arasında kliniğimizde takipli HIV ile enfekte, ≥18 yaş, ≥ 50 yaş erkek, postmenapozal kadın ve <40 yaş menapoza girmiş kadınlar çalışmaya dahil edildi. Kemik mineral yoğunluğu (KMY) sonuçları, kullandıkları ART’ler ve süreleri tarandı. Verilerin normal dağılımı Shapiro-Wilk testi ile değerlendirildi. Gruplar arası ve grup içi karşılaştırmalarda Mann-Whitney U, Kruskal-Wallis, Ki-kare ve Wilcoxon “signed-rank” testleri kullanıldı. Kriterlere uyan toplam 263 HIV ile enfekte bireyin 220’sinin en az bir KMY ölçümü mevcuttu. KMY 116 (%52) kişide normal, 84 (%38) kişide osteopenik ve 20 (%9) kişide osteoporotik olarak değerlendirildi. KMY normal tespit edilenlerin tenofovir alafenamid (TAF) kullanım süresi ortalama 10 ay iken, tenofovir disoproksil fumarat (TDF) kullanım süreleri ortalama 39 ay idi. Osteopeni/osteoporoz tespit edilenlerin TAF ve TDF kullanım süreleri sırasıyla ortalama 8 ve 32 ay olarak bulundu. En az bir kez KMY ölçümü yapılmış HIV ile yaşayan bireylerin %48’inde osteopeni ya da osteoporoz tespit edildiğini saptadık. Bu durum KMY taramasında rehberlerin önerilerine uyulmasındaki önemi göz önüne çıkarmaktadır.

Keywords

• İnsan immun yetmezlik virüsü
• HIV
• Kemik mineral yoğunluğu
• Osteopeni
• Osteoporoz

References

1. Beaupere C, Garcia M, Larghero J, Fève B, Capeau J, Lagathu C. The HIV proteins T at and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation. Aging cell 2015; 14: 534-46. doi: 10.1111/acel.12308
2. Biver E. Osteoporosis and HIV Infection. Calcified Tissue International 2022; 110: 624-40. doi: 10.1007/s00223-022-00946-4
3. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. Aids 2006; 20: 2165-74. doi: 10.1097/QAD.0b013e32801022eb
4. Bruera D, Luna N, David DO, Bergoglio LM, Zamudio J. Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy. Aids 2003; 17: 1917-23. doi: 10.1097/00002030-200309050-00010
5. Cotter EJ, Ip HSM, Powderly WG, Doran PP. Mechanism of HIV protein induced modulation of mesenchymal stem cell osteogenic differentiation. BMC Musculoskeletal Disorders 2008; 9: 1-12. doi: 10.1186/1471-2474-9-33
6. European AIDS Clinical Society (EACS) Guidelines 2021. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.eacsociety.org/media/final2021eacsguidelinesv11.0_oct2021.pdf
7. Gibellini D, De Crignis E, Ponti C, Cimatti L, Borderi M, Tschon M et al. HIV‐1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFα activation. Journal of medical virology 2008; 80: 1507-14. doi: 10.1002/jmv.21266
8. Gohda J, Ma Y, Huang Y, Zhang Y, Gu L, Han Y et al. HIV-1 replicates in human osteoclasts and enhances their differentiation in vitro. Retrovirology 2015; 12: 1-10. doi: 10.1186/s12977-015-0139-7

9. Hansen A, Obel N, Nielsen H, Pedersen C, Gerstoft J. Bone mineral density changes in protease inhibitor-sparing vs. nucleoside reverse transcriptase inhibitor-sparing highly active antiretroviral therapy: data from a randomized trial*. HIV Medicine 2011; 12: 157-65. doi: 10.1111/j.1468-1293.2010.00864.x
10. Imamichi H, Dewar RL, Adelsberger JW, Rehm CA, O’doherty U, Paxinos EE et al. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proceedings of the National Academy of Sciences 2016; 113: 8783-8. doi: 10.1073/pnas.1609057113
11. Imamichi H, Smith M, Adelsberger JW, Izumi T, Scrimieri F, Sherman BT et al. Defective HIV-1 proviruses produce viral proteins. Proceedings of the National Academy of Sciences 2020; 117: 3704-10. doi: 10.1073/pnas.1917876117
12. Komatsu A, Ikeda A, Kikuchi A, Minami C, Tan M, Matsushita S. Osteoporosis-related fractures in HIV-infected patients receiving long-term tenofovir disoproxil fumarate: an observational cohort study. Drug Safety 2018; 41: 843-8. doi: 10.1007/s40264-018-0665-z
13. Mayer KH, Hirsch HH, Kaufmann G, Sendi P, Battegay M. Immune reconstitution in HIV-infected patients. Clinical Infectious Diseases 2004; 38: 1159-66. doi: 10.1086/383034
14. Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. The Lancet infectious diseases 2010; 10: 251-61. doi: 10.1016/S1473-3099(10)70026-8
15. Nacher M, Serrano S, Gonzalez A, Hernández A, Mariñoso ML, Vilella R et al. Osteoblasts in HIV-infected patients: HIV-1 infection and cell function. Aids 2001; 15: 2239-43. doi: 10.1097/00002030-200111230-00004
16. Ofotokun I, Titanji K, Vunnava A, Roser-Page S, Vikulina T, Villinger F et al. Antiretroviral therapy induces a rapid increase in bone resorption that is positively associated with the magnitude of immune reconstitution in HIV infection. AIDS (London, England) 2016; 30: 405. doi: 10.1097/QAD.0000000000000918
17. Ofotokun I, Titanji K, Vikulina T, Roser-Page S, Yamaguchi M, Zayzafoon M et al. Role of T-cell reconstitution in HIV-1 antiretroviral therapy-induced bone loss. Nature communications 2015; 6: 8282. doi: 10.1038/ncomms9282
18. World Health Organization. (‎1998)‎. Guidelines for preclinical evaluation and clinical trials in osteoporosis. World Health Organization. https://iris.who.int/handle/10665/42088
19. Ponzetti M, Rucci N. Updates on osteoimmunology: what's new on the cross-talk between bone and immune system. Frontiers in endocrinology 2019; 10: 236. doi: 10.3389/fendo.2019.00236
20. Raynaud-Messina B, Bracq L, Dupont M, Souriant S, Usmani SM, Proag A et al. Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss. Proceedings of the National Academy of Sciences 2018; 115: E2556-E65. doi: 10.1073/pnas.1713370115
21. Tebas P, Powderly WG, Claxton S, Marin D, Tantisiriwat W, Teitelbaum SL, Yarasheski KE. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. Aids 2000; 14: F63-F7. doi: 10.1097/00002030-200003100-00005
22. Teichmann J, Stephan E, Lange U, Discher T, Friese G, Lohmeyer J et al. Osteopenia in HIV-infected women prior to highly active antiretroviral therapy. Journal of Infection 2003; 46: 221-7. doi: 10.1053/jinf.2002.1109
23. Türkiye Kemik Sağlığı Uzmanları IOFI. Türkiye’de kırıkları önlemek için çözümler. https://www.osteoporosis.foundation/sites/iofbonehealth/files/2023-08/2022_country_profile_turkey_turkish_final.pdf. (Erişim tarihi Mart 2023)
24. Yeni PG, Hammer SM, Carpenter CC, Cooper DA, Fischl MA, Gatell JM et al. Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel. JAMA 2002; 288: 222-35. doi: 10.1001/jama.288.2.222