Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda.
Intramuscular depot medroxyprogesterone acetate accentuates bone loss associated with tenofovir disoproxil fumarate-containing antiretroviral therapy initiation in young women living with HIV (the BONE: CARE study): a prospective cohort study in Uganda.
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DOI：
10.1016/s2214-109x(22)00080-8
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发表时间：
2022-05
影响因子：
34.3
通讯作者：
Brown, Todd T.
中科院分区：
文献类型：
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作者：
Matovu, Flavia Kiweewa;Kiwanuka, Noah;Nabwana, Martin;Scholes, Delia;Musoke, Philippa;Fowler, Mary Glenn;Beksinska, Mags E.;Pettifor, John M.;Brown, Todd T.
富马酸替诺福韦酯（TDF）和肌内长效醋酸甲羟孕酮（DMPA-IM）与骨密度（BMD）降低独立相关。我们的目的是评估DMPA-IM使用和TDF启动对BMD的年轻成年女性艾滋病毒感染者超过两年的综合影响，与年龄匹配的人没有艾滋病毒。Th骨：CARE研究是一项前瞻性队列研究，从乌干达坎帕拉的11个艾滋病毒护理和一般卫生机构招募了18-35岁的女性。根据HIV感染状况、TDF使用情况和DMPA-IM使用情况，将参与者分为四组，如下所示：（HIV阳性、DMPA阳性和TDF阳性）;在入组研究时，根据当地指南，使用DMPA-IM但不符合ART资格的HIV感染女性（HIV阳性、DMPA阳性和TDF阴性）;患有HIV的女性在没有DMPA-IM的情况下开始含TDF的ART（HIV阳性、DMPA阴性和TDF阳性）;以及使用非激素避孕药的没有HIV的对照（HIV阴性、DMPA阴性和TDF阴性）。在入组时和此后每6个月使用双能X线骨密度仪测量腰椎、全髋关节和股骨颈的BMD。我们评估了平均BMD的百分比变化。在2016年3月30日至2017年10月19日期间，我们招募了265名开始ART的HIV感染女性（159名DMPA-IM使用者和106名非激素避孕药使用者），187名使用DMPA-IM但不使用ART的HIV感染女性，以及69名未感染HIV的对照。平均年龄为26.1岁（SD 4.2）。接受TDF联合与不联合DMPA-IM治疗的HIV感染女性腰椎BMD较基线显著下降（-3.406% [95% CI -3.969至-2.844] vs -1统计学111%[-1.929至-0.293]; p<0.0001），全髋关节（-3统计学856%[-4.449至-3.264] vs -1统计学714%[-2.479至-0.949]; p=0.0002），股骨颈（-4.422% [-5.078至-3.766] vs -1统计999%[-3统计022至-0.976]; p= 0.0002），对照组腰椎增加（变化1.5%），全髋关节和股骨颈保持不变（变化-0统计1%）。同时使用TDF和DMPA-IM导致BMD下降显著更大（p<0·0001）（腰椎-2统计677%[95%CI-3统计743至-1.611]; p<0.0001;全髋关节-2.518% [-3.575至-1.461]; p<0.0001;股骨颈-2.907 [-4.132至-1.683]; p<0·0001）或对照组（腰椎-4.970% [-6.391 to -3.549]; p<0.0001;全髋-4.151% [-5.579 to -2.724]; p<0.0001;股骨颈-473%[-6.424 to -3.122]; p<0·0001）合并使用DMPA-IM导致HIV感染女性开始含TDF的ART时BMD损失加倍。应优先确定更安全的避孕和骨保留ART选择，以获得HIV感染女性的最佳护理。
Tenofovir disoproxil fumarate (TDF) and intramuscular depot medroxyprogesterone acetate (DMPA-IM) are independently associated with reduced bone mineral density (BMD). We aimed to assess the combined effects of DMPA-IM use and TDF initiation on BMD in young adult women living with HIV over two years, compared with age-matched people without HIV. Th BONE: CARE study was a prospective cohort study that recruited women aged 18–35 years from 11 HIV care and general health facilities in Kampala, Uganda. The participants were classified into four groups on the basis of their combination of HIV status, TDF use, and DMPA-IM use, as follows: women living with HIV initiating TDF-containing antiretroviral therapy (ART) with DMPA-IM (HIV positive, DMPA positive, and TDF positive); women living with HIV using DMPA-IM but not eligible for ART as per local guidelines at the time of enrolment into the study (HIV positive, DMPA positive, and TDF negative); women living with HIV initiating TDF-containing ART without DMPA-IM (HIV positive, DMPA negative, and TDF positive); and controls without HIV using non-hormonal contraceptives (HIV negative, DMPA negative, and TDF negative). BMD of the lumbar spine, total hip, and femoral neck were measured using semiannual dual-energy x-ray absorptiometry at enrolment and at intervals every 6 months thereafter. We assessed percentage change in mean BMD. Between March 30, 2016, and Oct 19, 2017, we enrolled 265 women living with HIV initiating ART (159 DMPA-IM users and 106 non-hormonal contraceptive users), 187 women living with HIV using DMPA-IM but not ART, and 69 controls without HIV. Mean age was 26·1 years (SD 4·2). BMD declined significantly from baseline in women living with HIV on TDF with versus without DMPA-IM at the lumbar spine (–3.406% [95% CI –3.969 to –2.844] vs –1·111% [–1.929 to –0.293]; p<0·0001), total hip (–3·856% [–4.449 to –3.264] vs –1·714% [–2.479 to –0.949]; p=0.0002), and femoral neck (–4.422% [–5.078 to –3.766] vs –1·999% [–3·022 to –0.976]; p=0·0002), increased in controls at the lumbar spine (1·5% change), and remained unchanged at total hip and femoral neck (–0·1% change). Concurrent use of TDF and DMPA-IM resulted in significantly greater BMD decline (p<0·0001) than TDF alone (lumbar spine –2·677% [95% CI –3·743 to –1.611]; p<0.0001; total hip –2.518% [–3.575 to –1.461]; p<0.0001; and femoral neck –2.907 [–4.132 to –1.683]; p<0·0001) or than controls (lumbar spine –4.970% [–6.391 to –3.549]; p<0·0001; total hip –4.151% [–5.579 to –2.724]; p<0.0001; and femoral neck –4·773% [–6.424 to –3.122]; p<0·0001) Concomitant DMPA-IM use resulted in a doubling of BMD loss in women living with HIV initiating TDF-containing ART. Identification of safer contraceptive and bone-sparing ART options should be prioritised for optimal care of women living with HIV.