Department of Medical Informatics and Biostatistics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department of Immunosuppressed, Clinical Hospital of Infectious Diseases, Cluj-Napoca, Romania.
PLoS One. 2021 Nov 16;16(11):e0260007. doi: 10.1371/journal.pone.0260007. eCollection 2021.
In this observational pilot study, we investigated the impact of Dolutegravir, Raltegravir, Elvitegravir (Integrase Strand Transfer Inhibitors, INSTIs), or boosted Darunavir (a Protease Inhibitor, PI) in combination with two nucleoside reverstranscriptase inhibitors (Emtricitabine/Tenofovir disoproxil or Lamivudine/Tenofovir disoproxil, NRTI) on four interleukins (IL-4, IL-10, IL-13, and IL-21) as immune activation markers in naïve HIV(Human Immunodeficiency Virus)-infected patients during the first six months of combined standard-of-care antiretroviral therapy (cART). Newly diagnosed with HIV-infected subjects and without any disease that could affect the immune activation markers were evaluated. The patients' physicians recommended the cART as standard-of-care and the ILs were measured before cART and six months of cART. The levels of CD4+ T-cells count and CD4+/CD8+ ratio significantly increased at six months (P-value<0.02) regardless of the drugs, INSTIs or PI. However, a CD4+/CD8+ >1 was observed in 25% of patients treated with Raltegravir and half of those treated with Dolutegravir. At six months of cART, viral load was detectable in only 6/31 individuals. IL-21 had an undetectable level in 30/31 patients after six months of cART. Our results suggest the potency in restoring immune markers in HIV-infected patients with all investigated drugs. Dolutegravir showed a tendency to statistically significant changes in IL-4 and IL-10. A clinical trial with random allocation of medication and an extensive follow-up is needed to replicate this research and validate the usefulness of evaluated ILs as markers of cART effectiveness.
在这项观察性的初步研究中，我们调查了整合酶抑制剂（INSTIs）中的多替拉韦、拉替拉韦、艾维雷格（Elvitegravir），或增效后的达芦那韦（蛋白酶抑制剂，PI）联合两种核苷逆转录酶抑制剂（恩曲他滨/替诺福韦二吡呋酯或拉米夫定/替诺福韦二吡呋酯，NRTI）对 4 种白细胞介素（IL-4、IL-10、IL-13 和 IL-21）作为免疫激活标志物的影响，在接受标准的抗逆转录病毒联合治疗（cART）的初治 HIV（人类免疫缺陷病毒）感染患者中。评估了新诊断为 HIV 感染的患者，且无任何可能影响免疫激活标志物的疾病。患者的医生建议将 cART 作为标准治疗，在 cART 之前和 cART 6 个月时测量白细胞介素。无论药物是 INSTIs 还是 PI，CD4+T 细胞计数和 CD4+/CD8+比值在 6 个月时均显著增加（P 值<0.02）。然而，用拉替拉韦治疗的患者中有 25%，用多替拉韦治疗的患者中有一半观察到 CD4+/CD8+>1。在 cART 6 个月时，只有 6/31 名个体的病毒载量可检测到。在 cART 6 个月后，31 名患者中有 30 名患者的白细胞介素 21 水平无法检测到。我们的结果表明，所有研究药物都能有效恢复 HIV 感染患者的免疫标志物。多替拉韦在白细胞介素 4 和白细胞介素 10 方面显示出统计学意义上的变化趋势。需要进行一项随机分配药物的临床试验，并进行广泛的随访，以复制这项研究，并验证所评估的白细胞介素作为 cART 有效性的标志物的有用性。
