在博茨瓦纳进行的一项随机试验中，对未感染艾滋病毒的年轻成年人使用替诺福韦-恩曲他滨或安慰剂进行暴露前预防，观察其骨矿物质密度的变化。
Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana.
作者信息
Kasonde Michael, Niska Richard W, Rose Charles, Henderson Faith L, Segolodi Tebogo M, Turner Kyle, Smith Dawn K, Thigpen Michael C, Paxton Lynn A
机构信息
Centers for Disease Control and Prevention- Botswana, HIV Prevention Research Unit, Gaborone, Botswana.
Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, Georgia, United States of America.
出版信息
PLoS One. 2014 Mar 13;9(3):e90111. doi: 10.1371/journal.pone.0090111. eCollection 2014.
BACKGROUND
Tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis (PrEP) has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD) loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women.
METHOD
We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18-29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA) scans at the hip, spine, and forearm.
RESULTS
A total of 220 participants (108 TDF-FTC, 112 placebo) had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8%) participants had low baseline BMD (z-score of <-2.0 at any anatomic site), including 3/114 women (2.6%) and 12/106 men (11.3%) (p = 0.02). Low baseline BMD was associated with being underweight (p = 0.02), having high blood urea nitrogen (p = 0.02) or high alkaline phosphatase (p = 0.03), and low creatinine clearance (p = 0.04). BMD losses of >3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0%) TDF-FTC vs. 26/79 (32.9%) placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm -0.84% (p = 0.01), spine -1.62% (p = 0.0002), hip -1.51% (p = 0.003)].
CONCLUSION
Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00448669.
背景
在多项临床试验中，替诺福韦-恩曲他滨（TDF-FTC）暴露前预防（PrEP）已被证明对预防HIV感染有效。两项针对男男性行为者的TDF PrEP研究显示骨矿物质密度（BMD）略有下降。我们调查了TDF以及TDF与激素避孕之间的相互作用对未感染HIV的非洲男性和女性BMD的影响。
方法
在博茨瓦纳TDF2 PrEP研究中，我们评估了18至29岁的异性恋男性和女性中，每日口服TDF-FTC与安慰剂相比对BMD的影响。参与者在基线时进行BMD测量，此后每隔6个月通过双能X线吸收法（DXA）扫描测量髋部、脊柱和前臂的BMD。
结果
共有220名参与者（108名接受TDF-FTC，112名接受安慰剂）在三个解剖部位进行了基线DXA BMD测量。15名（6.8%）参与者基线BMD较低（任何解剖部位的z评分<-2.0），包括3/114名女性（2.6%）和12/106名男性（11.3%）（p = 0.02）。基线BMD较低与体重过轻（p = 0.02）、血尿素氮升高（p = 0.02）或碱性磷酸酶升高（p = 0.03）以及肌酐清除率降低（p = 0.04）有关。基线后任何时间任何解剖部位BMD损失>3.0%的情况在TDF-FTC治疗组中显著更多[34/68（50.0%）TDF-FTC vs. 26/79（32.9%）安慰剂；p = 0.04]。在第30个月时，TDF-FTC与安慰剂相比，在所有三个部位BMD从基线的平均变化百分比存在小但显著的差异[前臂-0.84%（p = 0.01），脊柱-1.62%（p = 0.0002），髋部-1.51%（p = 0.003）]。
结论
使用TDF-FTC与前臂、髋部和腰椎的BMD出现小但具有统计学意义的下降有关。相当比例（6.8%）的健康博茨瓦纳年轻人基线BMD异常。需要对未感染HIV者长期使用TDF进行进一步评估。
试验注册
ClinicalTrials.gov NCT00448669。
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