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

TitleChanges in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir.
Publication TypeJournal Article
Year of Publication2015
AuthorsBrown TT, Moser C, Currier JS, Ribaudo HJ, Rothenberg J, Kelesidis T, Yang O, Dubé MP, Murphy RL, Stein JH, McComsey GA
JournalJ Infect Dis
Volume212
Issue8
Pagination1241-9
Date Published2015 Oct 15
ISSN1537-6613
KeywordsAdult, Anti-HIV Agents, Atazanavir Sulfate, Bone Density, Darunavir, Drug Therapy, Combination, Emtricitabine, Female, HIV, HIV Infections, HIV Integrase Inhibitors, HIV Protease Inhibitors, Humans, Male, Middle Aged, Raltegravir Potassium, Reverse Transcriptase Inhibitors, Ritonavir, Tenofovir, Viral Load, Young Adult
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.

DOI10.1093/infdis/jiv194
Alternate JournalJ. Infect. Dis.
PubMed ID25948863
PubMed Central IDPMC4577040
Grant List1UL1TR001111 / TR / NCATS NIH HHS / United States
2 UM1 AI068636-08 / AI / NIAID NIH HHS / United States
2 UM1 AI069503-08 / AI / NIAID NIH HHS / United States
2UM1 AI069418-08 / AI / NIAID NIH HHS / United States
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2UM1AI069439-08 / AI / NIAID NIH HHS / United States
5U01AI069471 / AI / NIAID NIH HHS / United States
5UM1AI069484-07 / AI / NIAID NIH HHS / United States
A1069424 / / PHS HHS / United States
AI 068636 / AI / NIAID NIH HHS / United States
AI 69501 / AI / NIAID NIH HHS / United States
AI-069471 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI069424 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
AI069439 / AI / NIAID NIH HHS / United States
AI069501 / AI / NIAID NIH HHS / United States
AI56933 / AI / NIAID NIH HHS / United States
AI69471 / AI / NIAID NIH HHS / United States
HL095126 / HL / NHLBI NIH HHS / United States
HL095132 / HL / NHLBI NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30AI050409 / AI / NIAID NIH HHS / United States
P30AI50410 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 TR000004 / TR / NCATS NIH HHS / United States
UL1 TR000445 / TR / NCATS NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UL1 TR001111 / TR / NCATS NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
UL1TR000170 / TR / NCATS NIH HHS / United States
UL1TR000439 / TR / NCATS NIH HHS / United States
UL1TR001079 / TR / NCATS NIH HHS / United States
UL1TR024160 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069423-08 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
UM1 AI069472 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI069532 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1AI069439 / AI / NIAID NIH HHS / United States
UM1AI069472 / AI / NIAID NIH HHS / United States
UM1AI069494 / AI / NIAID NIH HHS / United States
UM1AI68634 / AI / NIAID NIH HHS / United States
UMAI069481 / / PHS HHS / United States