Bone Mineral Density in HIV Participants Randomized to Raltegravir and Lopinavir/ritonavir Compared with Standard Second Line Therapy

Overview

Journal AIDS

Specialty Infectious Diseases

Date 2013 Aug 8

PMID 23921615

Citations 11

Authors

Allison Martin

Cecilia Moore

Patrick W G Mallon

Jennifer Hoy

Sean Emery

Waldo Belloso

Praphan Phanuphak

Samuel Ferret

David A Cooper

Mark A Boyd

Affiliations

Soon will be listed here.

Abstract

Objective: To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.

Design: 48-week open-label sub-study of the Second Line trial conducted in South Africa, India, Thailand, Malaysia and Argentina.

Methods: Dual energy X-ray absorptiometry scans of proximal femur and lumbar spine were performed at baseline and week 48. Linear regression was used to compare means of differences between arms. McNemars test compared osteopenia and osteoporosis. Associations between percentage BMD changes and baseline variables were assessed by multivariate linear regression.

Results: Two hundred and ten participants were randomized. Analyses were adjusted for sex, BMI and smoking status. Mean (95% CI) proximal femur BMD% reduced over 48 weeks by -5.2% (-6.7 to -3.8%) in the LPV/r+2-3N(t)RTIs arm and by -2.9% (-4.3 to -1.5%) in the LPV/r+RAL arm (P = 0.0001). Lumbar spine BMD reduced by -4.2% (-5.7 to -2.7%) in the LPV/r+2-3N(t)RTIs arm and by -2.0% (-3.5 to -0.6%) in the LPV/r+RAL arm (P = 0.0006). The incidence of osteopenia (7.6%) and osteoporosis (2.0%) assessed over 48 weeks were similar between arms. Reduced BMD over 48 weeks was significantly associated with longer duration of tenofovir on study [% change (SE) -1.58 (0.38) femur, -1.65 (0.38) spine, P = 0.0001] and low baseline BMI [% change (SE) 0.5 (0.13) femur, 0.17 (0.07) spine; P < 0.01].

Conclusion: An N(t)RTI-sparing antiretroviral regimen of LPV/r and raltegravir as second line therapy is associated with less bone loss than a LPV/r regimen containing N(t)RTIs.

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References

Jacobson D, Spiegelman D, Knox T, Wilson I . Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the nutrition for healthy living study. J Acquir Immune Defic Syndr. 2008; 49(3):298-308. PMC: 3930999. DOI: 10.1097/QAI.0b013e3181893e8e. View

Fux C, Rauch A, Simcock M, Bucher H, Hirschel B, Opravil M . Tenofovir use is associated with an increase in serum alkaline phosphatase in the Swiss HIV Cohort Study. Antivir Ther. 2009; 13(8):1077-82. View

Bolland M, Grey A, Gamble G, Reid I . CLINICAL Review # : low body weight mediates the relationship between HIV infection and low bone mineral density: a meta-analysis. J Clin Endocrinol Metab. 2007; 92(12):4522-8. DOI: 10.1210/jc.2007-1660. View

Gallant J, Staszewski S, Pozniak A, DeJesus E, Suleiman J, Miller M . Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004; 292(2):191-201. DOI: 10.1001/jama.292.2.191. View

Paul T, Asha H, Thomas N, Seshadri M, Rupali P, Abraham O . Hypovitaminosis D and bone mineral density in human immunodeficiency virus-infected men from India, with or without antiretroviral therapy. Endocr Pract. 2010; 16(4):547-53. DOI: 10.4158/EP09197.OR. View

Dolan S, Carpenter S, Grinspoon S . Effects of weight, body composition, and testosterone on bone mineral density in HIV-infected women. J Acquir Immune Defic Syndr. 2007; 45(2):161-7. DOI: 10.1097/QAI.0b013e31804a7f4d. View

Tebas P, Powderly W, Claxton S, Marin D, Tantisiriwat W, Teitelbaum S . Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS. 2000; 14(4):F63-7. PMC: 3170993. DOI: 10.1097/00002030-200003100-00005. View

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 Med. 2010; 12(3):157-65. DOI: 10.1111/j.1468-1293.2010.00864.x. View

Duvivier C, Kolta S, Assoumou L, Ghosn J, Rozenberg S, Murphy R . Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS. 2009; 23(7):817-24. DOI: 10.1097/QAD.0b013e328328f789. View

10.

Stellbrink H, Orkin C, Arribas J, Compston J, Gerstoft J, Van Wijngaerden E . Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis. 2010; 51(8):963-72. DOI: 10.1086/656417. View

11.

Haskelberg H, Hoy J, Amin J, Ebeling P, Emery S, Carr A . Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PLoS One. 2012; 7(6):e38377. PMC: 3376146. DOI: 10.1371/journal.pone.0038377. View

12.

McComsey G, Kitch D, Daar E, Tierney C, Jahed N, Tebas P . Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy.... J Infect Dis. 2011; 203(12):1791-801. PMC: 3100514. DOI: 10.1093/infdis/jir188. View

13.

Triant V, Brown T, Lee H, Grinspoon S . Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab. 2008; 93(9):3499-504. PMC: 2567857. DOI: 10.1210/jc.2008-0828. View

14.

van Vonderen M, Lips P, van Agtmael M, Hassink E, Brinkman K, Geerlings S . First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir. AIDS. 2009; 23(11):1367-76. DOI: 10.1097/QAD.0b013e32832c4947. View

15.

Bruera D, Luna N, David D, Bergoglio L, Zamudio J . Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy. AIDS. 2003; 17(13):1917-23. DOI: 10.1097/00002030-200309050-00010. View

16.

Boyd M, Kumarasamy N, Moore C, Nwizu C, Losso M, Mohapi L . Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen.... Lancet. 2013; 381(9883):2091-9. DOI: 10.1016/S0140-6736(13)61164-2. View

17.

Tomazic J, Ul K, Volcansek G, Gorensek S, Pfeifer M, Karner P . Prevalence and risk factors for osteopenia/osteoporosis in an HIV-infected male population. Wien Klin Wochenschr. 2007; 119(21-22):639-46. DOI: 10.1007/s00508-007-0844-x. View

18.

Grund B, Peng G, Gibert C, Hoy J, Isaksson R, Shlay J . Continuous antiretroviral therapy decreases bone mineral density. AIDS. 2009; 23(12):1519-29. PMC: 2748675. DOI: 10.1097/QAD.0b013e32832c1792. View

19.

Brown T, Qaqish R . Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006; 20(17):2165-74. DOI: 10.1097/QAD.0b013e32801022eb. View

20.

Mallon P . HIV and bone mineral density. Curr Opin Infect Dis. 2009; 23(1):1-8. DOI: 10.1097/QCO.0b013e328334fe9a. View