Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
J Acquir Immune Defic Syndr. 2021 Aug 15;87(5):1178-1186. doi: 10.1097/QAI.0000000000002723.
Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus.
In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with ≥2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus.
At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 ± 5 vs 49 ± 6 years). However, SHBG mean values were higher in MWH compared with those in HIV-seronegative men (65.6 ± 48.8 vs. 45.4 ± 22 nmol/L, P < 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4+ T-cell count [β= -0.02 (95% CI: -0.03 to -0.0002), P < 0.05], fewer cumulative years on zidovudine [β = -0.027 (95% CI: -0.045 to -0.009), P < 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [β = 0.022 (95% CI: 0.0006 to 0.04), P < 0.05].
Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation.
性激素结合球蛋白（SHBG）是一种糖蛋白，可调节性激素的生物利用度，并在普通人群中随年龄增长而增加。HIV 感染者的 SHBG 浓度较高，而 HIV 感染者被假设存在加速衰老。尚不清楚 SHBG 的纵向变化是否随时间增加，以及是否因 HIV 血清状态而异。
在一项纵向研究中，从艾滋病多中心队列研究中招募了 182 名 HIV 阳性男性（MWH）和 267 名 HIV 阴性男性（血清阴性），并按年龄、种族、地点和时间进行匹配，这些男性在接受高效抗逆转录病毒治疗（HAART）后 10 年内至少有 2 次 SHBG 血清样本。使用多变量线性混合效应回归模型评估 HIV 血清状态是否会影响对数转换后的 SHBG[ln（SHBG）]及其变化率。
在 MWH 中，平均年龄与 HIV 血清阴性男性相似（51±5 岁 vs. 49±6 岁）。然而，与 HIV 血清阴性男性相比，MWH 中的 SHBG 平均值更高（65.6±48.8 与 45.4±22 nmol/L，P<0.001）。在完全调整的模型中，SHBG 随时间增加，在 MWH 中的增加速度快于 HIV 血清阴性男性：分别为每年 2.0%（95%CI：1.4 至 2.7）和每年 1.3%（95%CI：0.8 至 1.8），P=0.038。在 MWH 中，较高的 SHBG 浓度与较低的 CD4+T 细胞计数显著相关[β=-0.02（95%CI：-0.03 至-0.0002），P<0.05]，与更少的累积齐多夫定年数[β=-0.027（95%CI：-0.045 至-0.009），P<0.001]和更多的非核苷类逆转录酶抑制剂药物累积年数[β=0.022（95%CI：0.0006 至 0.04），P<0.05]。
与衰老相关的 SHBG 增加在 MWH 中比在 HIV 血清阴性男性中更快，并且与较差的免疫状态和抗逆转录病毒药物暴露有关。这些发现的机制和后果需要进一步研究。
