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Effects of randomized rosuvastatin compared with placebo on bone and body composition among HIV-infected adults.
Erlandson, KM, Jiang, Y, Debanne, SM, McComsey, GA
AIDS (London, England). 2015;(2):175-82
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Abstract
BACKGROUND Statins have a beneficial effect on bone mineral density (BMD) and lean mass in some studies of HIV-uninfected adults; however, this has never been investigated in the setting of HIV infection. DESIGN HIV-infected individuals on stable antiretroviral therapy with a low-density lipoprotein cholesterol level of 130 mg/dl or less and evidence of heightened immune activation or inflammation were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. METHODS This was a prespecified interim analysis at 48 weeks. Between-group and within-group differences were compared; multivariable regression models were constructed. RESULTS Seventy-two individuals were randomized to statin therapy and 75 to placebo. Modest 48-week relative increases in trochanter BMD [0.9%; 95% confidence interval (95% CI) -0.9 to 0.6] and total hip BMD (0.6%; 95% CI 0.0-1.1) in the statin arm were significantly greater than placebo (P < 0.05). The relationship between statin use and total hip BMD change was robust to adjustment of age, sex, race and smoking status (P = 0.02) and strengthened by inclusion of baseline (P = 0.01) and week 48 change in soluble tumour necrosis factor-α receptor (sTNFR)-1 (P = 0.009). Relative increases in total body, trunk and limb fat were similar between statin and placebo arms (P ≥ 0.58). Although a significant gain in leg lean mass was seen in the statin arm, this was not significantly different compared with placebo (P = 0.36). CONCLUSION The improvements seen in total hip BMD after 48 weeks of rosuvastatin therapy support further potential benefits of statin therapy in HIV, beyond a reduction of cardiovascular risk.
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Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir.
Brown, TT, Moser, C, Currier, JS, Ribaudo, HJ, Rothenberg, J, Kelesidis, T, Yang, O, Dubé, MP, Murphy, RL, Stein, JH, et al
The Journal of infectious diseases. 2015;(8):1241-9
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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.
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Vitamin D deficiency and altered bone mineral metabolism in HIV-infected individuals.
Eckard, AR, McComsey, GA
Current HIV/AIDS reports. 2014;(3):263-70
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Abstract
Although patients with HIV infection are living decades longer than before with the advent of combination antiretroviral therapy, they have an increased rate of co-morbidities associated with chronic HIV, such as osteoporosis, cardiovascular disease, and immune dysfunction. Many of these complications are known to be affected by vitamin D status in the general population. Thus, the high rate of vitamin D deficiency among HIV-infected patients is alarming. Many observational and cohort studies have demonstrated that vitamin D deficiency is associated with these HIV-related complications, but randomized, placebo-controlled trials are limited. This paper reviews recent data on vitamin D deficiency in HIV infection.