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Randomized Controlled Trial
. 2015 Oct 15;212(8):1241-9.
doi: 10.1093/infdis/jiv194. Epub 2015 May 5.

Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir

Todd T Brown  1 , Carlee Moser  2 , Judith S Currier  3 , Heather J Ribaudo  2 , Jennifer Rothenberg  4 , Theodoros Kelesidis  3 , Otto Yang  3 , Michael P Dubé  5 , Robert L Murphy  6 , James H Stein  7 , Grace A McComsey  8
Affiliations
Randomized Controlled Trial

Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir

Todd T Brown et al. J Infect Dis. .

Erratum in

Abstract

Background: Specific antiretroviral therapy (ART) medications and the severity of human immunodeficiency virus (HIV) disease before treatment contribute to bone mineral density (BMD) loss after ART initiation.

Methods: We compared the percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). We also determined whether baseline levels of inflammation markers and immune activation were independently associated with BMD loss.

Results: At week 96, the mean percentage changes from baseline in spine and hip BMDs were similar in the protease inhibitor (PI) arms (spine: -4.0% in the ATV/r group vs -3.6% in the DRV/r [P = .42]; hip: -3.9% in the ATV/r group vs -3.4% in the DRV/r group [P = .36]) but were greater in the combined PI arms than in the RAL arm (spine: -3.8% vs -1.8% [P < .001]; hip: -3.7% vs -2.4% [P = .005]). In multivariable analyses, higher baseline concentrations of high-sensitivity C-reactive protein, interleukin 6, and soluble CD14 were associated with greater total hip BMD loss, whereas markers of CD4(+) T-cell senescence and exhaustion (CD4(+)CD28(-)CD57(+)PD1(+)) and CD4(+) T-cell activation (CD4(+)CD38(+)HLA-DR(+)) were associated with lumbar spine BMD loss.

Conclusions: BMD losses 96 weeks after ART initiation were similar in magnitude among patients receiving PIs, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and immune activation/senescence before ART initiation independently predicted subsequent BMD loss.

Keywords: bone mineral density; human immunodeficiency virus; inflammation; integrase inhibitor; protease inhibitor.

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Figures

Figure 1.
Figure 1.
Subject disposition. Abbreviations: ART, antiretroviral therapy; BMD, bone mineral density; ITT, intention to treat; NRTI, nucleoside reverse transcriptase inhibitor; r, ritonavir.
See this image and copyright information in PMC

References

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