Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet - University of Copenhagen, Blegdamsvej 9B, DK-2100, Copenhagen Ø, Denmark.
HIV Epidemiology and Biostatistics Unit, Department of Infection and Population Health, UCL, London, UK.
BMC Infect Dis. 2019 Aug 9;19(1):708. doi: 10.1186/s12879-019-4347-y.
Thymidine analogues (TA) and didanosine (ddI) are associated with long-lasting adipose tissue redistribution. Adiponectin is a widely used marker of adipocyte activity, and adipose tissue density assessed by CT-scan is associated with adipocyte size and function. We hypothesized that prior exposure to TA and ddI was associated with long-lasting adipose tissue dysfunction in people living with HIV (PLWH). Thus, we tested possible associations between markers of adipose tissue dysfunction (adipose tissue density and adiponectin) and prior exposure to TA and/or ddI, years after treatment discontinuation.
Eight hundred forty-eight PLWH from the COCOMO study were included and stratified according to prior exposure to TA and/or ddI (with, n = 451; without n = 397). Visceral (VAT) and subcutaneous (SAT) adipose tissue area and density were determined by single slice abdominal CT-scan at lumbar 4th level. Venous blood was collected and analyzed for adiponectin. Multivariable linear and logistic regression analyses were used to test our hypotheses. Multivariable models were adjusted for age, sex, smoking, origin, physical activity, BMI, and adipose tissue area (VAT or SAT area, accordingly to the outcome).
prior exposure to TA and/or ddI was associated with excess risk of low VAT (adjusted OR (aOR) 1.74 [1.14; 2.67]) and SAT density (aOR 1.74 [1.18; 2.58]), for a given VAT and SAT area, respectively. No association between VAT and SAT density with time since TA and/or ddI discontinuation was found. 10 HU increase in VAT density was associated with higher adiponectin plasma level and this association was not modified by prior exposure to TA and/or ddI. Prior exposure to TA and/or ddI was associated with 9% lower [- 17;-2] plasma adiponectin levels and with excess risk of low adiponectin (aOR 1.74 [1.10; 2.76]).
We described low adipose tissue density and impaired adiponectin production to be associated with prior exposure to TA and/or ddI even years after treatment discontinuation and independently of adipose tissue area. These findings suggest that prior TA and ddI exposure may have long-lasting detrimental effects on adipose tissue function and, consequently, on cardiometabolic health in PLWH.
胸苷类似物（TA）和去羟肌苷（ddI）与持久的脂肪组织再分布有关。脂联素是脂肪细胞活性的广泛使用标志物，CT 扫描评估的脂肪组织密度与脂肪细胞大小和功能有关。我们假设，在停止治疗多年后，先前接触 TA 和/或 ddI 与艾滋病毒感染者（PLWH）的持久脂肪组织功能障碍有关。因此，我们测试了脂肪组织功能障碍标志物（脂肪组织密度和脂联素）与先前接触 TA 和/或 ddI 之间的可能关联。
共纳入 848 名来自 COCOMO 研究的 PLWH，并根据先前接触 TA 和/或 ddI 进行分层（接触组，n=451；未接触组，n=397）。通过腰椎 4 水平的单次腹部 CT 扫描确定内脏（VAT）和皮下（SAT）脂肪组织面积和密度。采集静脉血并分析脂联素。使用多元线性和逻辑回归分析来检验我们的假设。多变量模型调整了年龄、性别、吸烟、原籍、体力活动、BMI 和脂肪组织面积（VAT 或 SAT 面积，根据结果而定）。
先前接触 TA 和/或 ddI 与低 VAT（调整后的 OR（aOR）1.74 [1.14；2.67]）和 SAT 密度（aOR 1.74 [1.18；2.58]）的风险增加相关，对于给定的 VAT 和 SAT 面积分别。未发现 VAT 和 SAT 密度与 TA 和/或 ddI 停药后时间之间的关联。VAT 密度每增加 10 HU，脂联素的血浆水平就会升高，这种关联不受先前接触 TA 和/或 ddI 的影响。先前接触 TA 和/或 ddI 与血浆脂联素水平降低 9%相关[-17；-2]，并且存在低脂联素的风险增加（aOR 1.74 [1.10；2.76]）。
我们描述了低脂肪组织密度和脂联素产生受损与先前接触 TA 和/或 ddI 有关，即使在治疗停止多年后也是如此，并且与脂肪组织面积无关。这些发现表明，先前接触 TA 和 ddI 可能对脂肪组织功能产生持久的有害影响，从而对 PLWH 的心血管代谢健康产生影响。
