Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: Effects on virologic, immunologic, and toxicity parameters
Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: Effects on virologic, immunologic, and toxicity parameters
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DOI：
10.1073/pnas.261568398
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发表时间：
2001-12-18
影响因子：
11.1
通讯作者：
Fauci, AS
中科院分区：
文献类型：
--
作者：
Dybul, M;Chun, TW;Fauci, AS
尽管持续高效抗逆转录病毒疗法(HAART)对许多艾滋病毒感染患者有效，但它可能是有毒的，而且成本高昂。通过减少患者接受药物治疗的总时间，间歇性HAART可以降低毒性和成本。因此，我们启动了一项初步研究，其中10名HIV感染者接受有效治疗，每毫升血浆中HIV RNA水平为50拷贝，全血中CD4(+)T细胞计数为300细胞/mm(3)，接受HAART治疗7天，然后停止HAART 7天。3例维持血浆病毒血症抑制32-68周。外周血或淋巴结单个核细胞中的HIV前病毒DNA或复制能力强的HIV或外周血中的HIV RNA均未显著增加。CD4(+)T细胞计数没有显著变化，表达活化标志或产生干扰素-γ的CD4(+)或CD8(+)T细胞对HIV的反应没有显著增加，CD4(+)T细胞对p24抗原的增殖没有增加，也没有证据表明对HAART药物产生耐药性。血清胆固醇和甘油三酯水平显著降低。因此，在这项概念验证研究中，短周期间歇性HAART在保持CD4(+)T细胞计数的同时，保持了对血浆病毒血症和储存部位艾滋病毒复制的抑制。此外，血清胆固醇和甘油三酯水平也有所下降。间歇治疗可能是降低HIV感染者成本和毒性的重要策略。
Although continuous highly active antiretroviral therapy (HAART) is effective for many HIV-infected patients, it can be toxic and prohibitive in cost. By decreasing the total amount of time patients receive medications, intermittent HAART could reduce toxicity and cost. Therefore, we initiated a pilot study in which 10 HIV-infected individuals receiving effective therapy that resulted in levels of HIV RNA < 50 copies per ml of plasma and CD4(+) T cell counts > 300 cells per mm(3) of whole blood received repeated cycles of 7 days on HAART followed by 7 days off of HAART. Patients maintained suppression of plasma viremia for 32-68 weeks. There was no significant increase in HIV proviral DNA or replication-competent HIV in peripheral CD4(+) T cells or HIV RNA in peripheral blood or lymph node mononuclear cells. There was no significant change in CD4(+) T cell counts, no significant increase in CD4(+) or CD8(+) T cells expressing activation markers or producing IFN-gamma in response to HIV, no increase in CD4(+) T cell proliferation to p24 antigen, and no evidence for the development of resistance to HAART medications. There was a significant decrease in serum cholesterol and triglyceride levels. Thus, in this proof-of-concept study, short-cycle intermittent HAART maintained suppression of plasma viremia as well as HIV replication in reservoir sites while preserving CD4(+) T cell counts. In addition, there was a decrease in serum cholesterol and triglyceride levels. Intermittent therapy may be an important strategy to reduce cost and toxicity for HIV-infected individuals.