Reduction of HIV-1 in blood and lymph nodes following potent antiretroviral therapy and the virologic correlates of treatment failure.
Reduction of HIV-1 in blood and lymph nodes following potent antiretroviral therapy and the virologic correlates of treatment failure.
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DOI：
10.1073/pnas.94.23.12574
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发表时间：
1997-11
影响因子：
11.1
通讯作者：
J. Wong;H. Günthard;D. Havlir;Zhi Qiang Zhang;A. Haase;C. Ignacio;S. Kwok;E. Emini;D. Richman
中科院分区：
文献类型：
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作者：
J. Wong;H. Günthard;D. Havlir;Zhi Qiang Zhang;A. Haase;C. Ignacio;S. Kwok;E. Emini;D. Richman
有效的抗逆转录病毒治疗可使血浆HIV RNA水平在一年或更长时间内降低到检测阈值以下。在血浆中HIV RNA水平抑制超过6个月的患者中，淋巴组织中HIV RNA减少的程度尚未确定。我们评估了10名接受了36-52周的因地那韦(IDV)/齐多夫定(ZDV)/拉米夫定（3TC）、IDV或ZDV/3TC治疗的HIV感染者的血液和腹沟淋巴结活检中HIV RNA和DNA的水平，并鉴定了耐药突变。治疗1年后，LN中的病毒RNA水平仍可检测到，但比中断治疗的三联用药方案的受试者或单独接受ZDV/3TC治疗的受试者低log10 = 4，后者淋巴结中的病毒载量与未治疗患者的病毒载量难以区分。在所有病例中，在淋巴结和外周血单核细胞（PBMC）中仍可检测到病毒DNA。当血浆病毒抑制不完全时，淋巴结和PBMC培养呈阳性，产生耐药性。这些研究表明，有效的抗逆转录病毒联合治疗对血浆病毒血症的显著和持续抑制与治疗后1年淋巴结中的低HIV RNA水平有关。相反，在治疗一年后，即使是适度的血浆病毒水平持续存在，也反映了病毒正在进行复制，出现耐药性，以及淋巴结中病毒的高负荷维持。
Potent antiretroviral therapy can reduce plasma HIV RNA levels below the threshold of detection for periods of a year or more. The magnitude of HIV RNA reduction in the lymphoid tissue in patients with suppression of HIV RNA levels in plasma beyond 6 months has not been determined. We evaluated levels of HIV RNA and DNA and characterized resistance mutations in blood and inguinal lymph node biopsies obtained from 10 HIV-infected subjects who received 36-52 weeks of indinavir (IDV)/zidovudine (ZDV)/lamivudine (3TC), IDV, or ZDV/3TC. After 1 year of therapy, viral RNA levels in LN of individuals remained detectable but were log10 = 4 lower than in subjects on the triple drug regimen with interruption of therapy or in those treated with ZDV/3TC alone, who had viral loads in their lymph nodes indistinguishable from those expected for untreated patients. In all cases viral DNA remained detectable in lymph nodes and peripheral blood mononuclear cells (PBMC). When plasma virus suppression was incomplete, lymph node and PBMC cultures were positive and drug resistance developed. These studies indicate that pronounced and sustained suppression of plasma viremia by a potent antiretroviral combination is associated with low HIV RNA levels in the lymph nodes 1 year after treatment. Conversely, the persistence of even modest levels of plasma virus after 1 year of treatment reflects ongoing viral replication, the emergence of drug resistance, and the maintenance of high burdens of virus in the lymph nodes.