Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration
Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration
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DOI：
10.1093/infdis/jis663
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发表时间：
2013-01-15
影响因子：
6.4
通讯作者：
Montaner, Luis J.
中科院分区：
文献类型：
--
作者：
Azzoni, Livio;Foulkes, Andrea S.;Montaner, Luis J.
背景抗逆转录病毒疗法（ART）介导的免疫重建不能恢复免疫系统自发控制人类免疫缺陷病毒（HIV）复制的能力。共有23名接受ART（CD 4（+）T细胞计数，> 450个细胞/μ L）的HIV 1型（HIV-1）感染、病毒学抑制受试者被随机分配接受180 μ g/周（A组）或90 μ g/周（B组）在其当前ART方案中添加聚乙二醇化（Peg）干扰素α-2a（对于臂B）。5周后，ART中断，聚乙二醇干扰素α-2a持续长达12周（主要终点），可选择继续至24周。终点包括病毒学失败（病毒载量，>= 400拷贝/mL）和不良事件。残留病毒载量和HIV-1 DNA整合也进行了评估。在聚乙二醇干扰素α-2a单药治疗的第12周，20例受试者中有9例（45%）观察到病毒抑制，这一比例显著高于预期（A组，P = 0.0088; B组，P = 0.0010;联合组，P <0.0001）。在24周内，与历史对照组的受试者比例相比，两组的病毒载量受试者比例均较低（A组，P = 0.0046; B组，P = 0.0011）。与发生终点失败的受试者相比，持续病毒载量<400拷贝/mL的受试者整合HIV DNA水平降低（P = 0.0313），但残留病毒载量增加（P = 0.0078）。聚乙二醇干扰素α-2a免疫治疗导致HIV复制的控制和HIV-1整合的减少，支持免疫介导的方法在HIV抑制和/或根除中的作用。
Background. Antiretroviral therapy (ART)-mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication.Methods. A total of 23 HIV type 1 (HIV-1)-infected, virologically suppressed subjects receiving ART (CD4(+) T-cell count, >450 cells/mu L) were randomly assigned to have 180 mu g/week (for arm A) or 90 mu g/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg-interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, >= 400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed.Results. At week 12 of Peg-interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P < .0001). Over 24 weeks, both arms had lower proportions of subjects who had viral load, compared with the proportion of subjects in a historical control group (arm A, P = .0046; arm B, P = .0011). Subjects who had a sustained viral load of < 400 copies/mL had decreased levels of integrated HIV DNA (P = .0313) but increased residual viral loads (P = .0078), compared with subjects who experienced end-point failure.Conclusions. Peg-interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication.