In the pilot NCT01935089 trial, we tested whether pegylated interferon alpha2b (Peg-IFN-α2b) with antiretroviral therapy (ART) was safe and could impact HIV and immune measures in blood and in gut-associated lymphoid tissue (GALT). Twenty HIV-1⁺ ART-suppressed individuals received 1 μg/kg/week Peg-IFN-α2b with ART for 20 weeks, with intermediate 4-week analytical ART interruption (ATI). Safety, immune activation, HIV viral load and integrated HIV DNA in blood, and HIV RNA and DNA in gut biopsies were measured. A total of 7/20 participants experienced grade 3–4 adverse events, while 17/20 participants completed the study. Of the 17 participants who completed the study, 8 remained suppressed during ATI, while all 17 were suppressed at end of treatment (EoT). As expected, treatment increased activation of T and natural killer (NK) cells and IFN-stimulated molecule expression on monocytes in periphery. While circulating CD4⁺ T cells showed a trend for a decrease in integrated HIV DNA, GALT showed a significant decrease in HIV-1 RNA⁺ cells as measured by in situ hybridization along with a reduction in total HIV DNA and cell-associated RNA by EoT. The observed decrease in HIV-1 RNA⁺ cells in GALT was positively associated with the decrease in activated NK cells and macrophages. This study documents for the first time that 20 weeks of immunotherapy with Peg-IFN-α2b+ART (inclusive of a 4-week ATI) is safe and results in an increase in blood and GALT immune activation and in a significant decrease in HIV-1 RNA⁺ cells in GALT in association with changes in innate cell activation.

中文翻译：

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聚乙二醇干扰素 Alpha 2b 在抗逆转录病毒治疗抑制个体中的安全性、免疫和抗病毒作用：临床试验结果

在 NCT01935089 试点试验中，我们测试了聚乙二醇化干扰素 α2b (Peg-IFN-α2b) 与抗逆转录病毒疗法 (ART) 是否安全，并可能影响血液和肠道相关淋巴组织 (GALT) 中的 HIV 和免疫措施。二十个 HIV-1 ⁺ART 抑制个体接受 1 μg/kg/周 Peg-IFN-α2b 与 ART 共 20 周，中间 4 周分析性 ART 中断 (ATI)。测量了安全性、免疫激活、HIV 病毒载量和血液中整合的 HIV DNA，以及肠道活检中的 HIV RNA 和 DNA。共有 7/20 名参与者经历了 3-4 级不良事件，而 17/20 名参与者完成了研究。在完成研究的 17 名参与者中，8 名在 ATI 期间仍然受到抑制，而所有 17 名在治疗结束 (EoT) 时均受到抑制。正如预期的那样，治疗增加了 T 细胞和自然杀伤 (NK) 细胞的活化以及外周单核细胞上 IFN 刺激的分子表达。虽然循环 CD4 ^{+ T 细胞显示整合 HIV DNA 减少的趋势，但 GALT 显示 HIV-1 RNA +}显着减少通过原位杂交测量的细胞以及 EoT 的总 HIV DNA 和细胞相关 RNA 的减少。在 GALT 中观察到的 HIV-1 RNA ⁺细胞的减少与活化的 NK 细胞和巨噬细胞的减少呈正相关。该研究首次证明，使用 Peg-IFN-α2b+ART（包括 4 周 ATI）进行 20 周免疫治疗是安全的，并导致血液和 GALT 免疫激活增加，并显着降低 HIV- 1 GALT 中的 RNA ⁺细胞与先天细胞活化的变化有关。