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

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.