Determining Bone Loss and Bone Mineral Density Recovery Following Repeat Pregnancy/Lactation Among HIV Women on ART

确定接受 ART 治疗的 HIV 妇女重复怀孕/哺乳后的骨质流失和骨矿物质密度恢复情况

• 批准号: 10805834
• 负责人: MARY Glenn Fowler
• 金额: $ 22.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10805834
• 关键词: Administrative Supplement; Affect; Biological Markers; Birth; Bone Density; Breast Feeding; COVID-19 pandemic; Calcium; Cohort Studies; Data; Dual-Energy X-Ray Absorptiometry; Enrollment; Follow-Up Studies; Goals; Grant; HIV; HIV Seronegativity; Infant; Lactation; Life; Malawi; Maternal Health; Measures; Metabolic; Milk; Minerals; Mothers; Nevirapine; Osteopenia; Osteoporosis; Outcome; Participant; Pattern; Pregnancy; Pregnant Women; Prophylactic treatment; Randomized; Recovery; Reporting; Risk; Risk Factors; Scanning; Site; Tenofovir; Time; Uganda; Woman; adverse outcome; age group; antiretroviral therapy; bone; bone health; bone loss; clinical research site; clinical risk; cohort; follow-up; parity; prospective

PROJECT SUMMARY / ABSTRACT Among HIV-infected women, the longer-term impact that lifetime antiretroviral therapy (ART) with repeat pregnancy followed by breastfeeding has on maternal health outcomes including bone mineral density (BMD), in particular, remains unknown. Findings from the PROMISE 1077BF trial indicated that BMD significantly decreased among asymptomatic HIV-infected mothers randomized to receive ART during extended breastfeeding compared to mothers whose infants were randomized to receive nevirapine prophylaxis during breastfeeding. Breastfeeding was also associated with transient decreases in BMD but was usually followed by BMD recovery. Lactating women with HIV taking tenofovir-based ART had altered milk mineral composition (i.e. calcium) when compared to women without HIV. These initial results from the PROMISE trial reporting BMD decreases with ART during breastfeeding and metabolic differences for lactating mothers on ART from the Gumba study raise concerns about potentially increased risk of early osteopenia or osteoporosis compared to mothers are not HIV-infected and not exposed to lifetime ART. To better understand this relationship, the Maternal Bone Health Study (MBHS) is a prospective longitudinal follow up study being conducted to assess BMD changes with repeat pregnancy and extended breastfeeding among HIV-infected mothers from the PROMISE trial who are now enrolled as participants in the PROMOTE cohort. This observational MBHS is being conducted at clinical research sites in Blantyre, Malawi and Kampala, Uganda to explore factors which may affect bone health and both loss and recovery patterns of BMD for HIV-infected women on lifetime ART. The Specific Aims of the MBHS are: (1) to gather baseline BMD data at entry into PROMOTE and to compare to prior bone density scans, DXA measures, from PROMISE in order to assess changes clinical risk factors for low BMD in HIV-infected women and (2) to determine BMD loss and recovery patterns in from bone biomarker changes during a 36-month post-delivery period among HIV-infected women who have a repeat pregnancy during PROMOTE follow up with results being compared to age group- and parity-matched HIV-negative pregnant women at each site. Lastly, the MBHS will aim (3) to compare BMD and bone biomarker findings with PROMOTE mothers matched for age group and parity by site who do not conceive during 36 months of follow-up. These comparisons will elucidate whether decreases in BMD among HIV-infected mothers on lifetime ART are exacerbated with repeat pregnancy/breastfeeding and if BMD recovery after breastfeeding is further decreased when compared to HIV-negative women at the end of breastfeeding. The long-term goal of this cohort study is to better support the bone health of breastfeeding women living with HIV who are on lifetime ART. The requested administrative supplement will allow completion of the crucial 36 month outcomes.

项目摘要/摘要 在感染艾滋病毒的妇女中，终生抗逆转录病毒治疗（ART） 母乳喂养后重复妊娠对包括骨矿物质在内的孕产妇健康结局的影响 密度（BMD），特别是，仍然未知。PROMISE 1077 BF试验的结果表明， 随机接受抗逆转录病毒治疗的无症状HIV感染母亲的BMD显著降低 在延长母乳喂养期间， 母乳喂养期间预防奈韦拉平。母乳喂养也与短暂的减少有关 但通常随后BMD恢复。哺乳期妇女与艾滋病毒服用替诺福韦为基础 与没有艾滋病毒的妇女相比，ART改变了牛奶矿物质成分（即钙）。 这些来自PROMISE试验的初步结果报告了母乳喂养期间ART会降低BMD， Gumba研究中接受ART的哺乳期母亲的代谢差异引起了人们的担忧， 与未感染艾滋病毒的母亲相比，早期骨质减少或骨质疏松症的风险可能增加 为了更好地了解这种关系，母亲的骨骼健康 研究（MBHS）是一项前瞻性纵向随访研究，旨在评估 在PROMISE试验中， 现在被登记为PROMOTE队列的参与者。这项观察性的MBHS正在进行， 在马拉维的布兰太尔和乌干达的坎帕拉的临床研究中心，探索可能影响 骨健康和骨密度的损失和恢复模式的艾滋病毒感染的妇女终身抗逆转录病毒治疗。 MBHS的具体目标是：（1）在进入PROMOTE时收集基线BMD数据， 与PROMISE的既往骨密度扫描、DXA测量进行比较，以评估临床变化 HIV感染妇女低BMD的危险因素;（2）确定 在分娩后36个月期间， 在PROMOTE随访期间再次怀孕，并将结果与年龄组进行比较-以及 每个研究中心的产次匹配的艾滋病毒阴性孕妇。最后，MBHS的目标是（3）比较 按研究中心列出的年龄组和产次匹配的PROMOTE母亲的BMD和骨生物标志物结果 在36个月的随访中没有怀孕。这些比较将阐明， 接受终生抗逆转录病毒治疗的艾滋病毒感染母亲的骨密度下降随着重复治疗而加剧。 妊娠/母乳喂养，如果母乳喂养后BMD恢复进一步下降， 艾滋病毒阴性的妇女在母乳喂养结束时。这项队列研究的长期目标是更好地 支持终生接受抗逆转录病毒治疗的感染艾滋病毒的哺乳期妇女的骨骼健康。 所要求的行政补充将使关键的36个月的结果得以完成。