Bloch M, Tong W W Y, Hoy J, Baker D, Lee F J, Richardson R, Carr A
Holdsworth House Medical Practice, Sydney, NSW, Australia.
HIV Med. 2014 Jul;15(6):373-80. doi: 10.1111/hiv.12123. Epub 2014 Jan 26.
Tenofovir, particularly when given with a ritonavir-boosted protease inhibitor (rPI), reduces bone mineral density (BMD) and increases bone turnover markers (BTMs), both of which are associated with increased fracture risk. Raltegravir has not been associated with bone loss.
In an open-label, nonrandomized, pilot study, tenofovir was switched to raltegravir in adults also receiving a rPI for at least 6 months with a spine or hip T-score ≤ -1.0 and plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 3 months. The primary endpoint was BMD change by dual-energy X-ray absorptiometry. Student's paired t-test was used to compare continuous variables. Factors associated with BMD increase were assessed using linear regression.
Thirty-seven patients were enrolled in the study: 97% were male, the mean age was 49 years, the mean T-scores were -1.4 (spine) and -1.3 (total left hip), and the mean tenofovir treatment duration was 3.1 years. BMD increases were significant at weeks 24 and 48. At week 48, spine BMD increased by 3.0% [95% confidence interval (CI) 1.9, 4.0%; P < 0.0001] and left total hip BMD increased by 2.5% (95% CI 1.6, 3.3%; P < 0.0001). BTMs (N-telopeptide, osteocalcin and bone alkaline phosphatase) all decreased significantly at week 24 (P ≤ 0.0017). There were no raltegravir-related serious or grade 3-4 adverse events. HIV viral load remained <50 copies/mL plasma on raltegravir/rPI therapy.
Switching virologically suppressed HIV-infected adults with low BMD taking an rPI from tenofovir to raltegravir was safe and significantly improved hip and spine BMD and reduced markers of bone turnover over 48 weeks.
替诺福韦，尤其是与利托那韦增强的蛋白酶抑制剂（rPI）联用时，会降低骨矿物质密度（BMD）并增加骨转换标志物（BTMs），这两者均与骨折风险增加相关。拉替拉韦与骨质流失无关。
在一项开放标签、非随机的试点研究中，对于脊柱或髋部T值≤ -1.0且血浆HIV RNA < 50 HIV-1 RNA拷贝/mL至少3个月、同时接受rPI治疗至少6个月的成人，将替诺福韦换用为拉替拉韦。主要终点是通过双能X线吸收法测定的BMD变化。采用学生配对t检验比较连续变量。使用线性回归评估与BMD增加相关的因素。
37名患者纳入研究：97%为男性，平均年龄49岁，平均T值分别为-1.4（脊柱）和-1.3（左侧全髋），替诺福韦平均治疗时长为3.1年。在第24周和第48周时BMD增加显著。在第48周时，脊柱BMD增加了3.0% [95%置信区间（CI）1.9，4.0%；P < 0.0001]，左侧全髋BMD增加了2.5%（95% CI 1.6，3.3%；P < 0.0001）。BTMs（N-端肽、骨钙素和骨碱性磷酸酶）在第24周时均显著下降（P ≤ 0.0017）。没有与拉替拉韦相关的严重或3 - 4级不良事件。在拉替拉韦/rPI治疗期间，HIV病毒载量仍保持在<50拷贝/mL血浆水平。
对于病毒学抑制的、服用rPI且BMD较低的HIV感染成人，将替诺福韦换用为拉替拉韦是安全的，并且在48周内显著改善了髋部和脊柱的BMD，并降低了骨转换标志物。
