Wong J K, Günthard H F, Havlir D V, Zhang Z Q, Haase A T, Ignacio C C, Kwok S, Emini E, Richman D D
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12574-9. doi: 10.1073/pnas.94.23.12574.
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.
强效抗逆转录病毒疗法可使血浆中HIV RNA水平在一年或更长时间内降至检测阈值以下。血浆中HIV RNA水平抑制超过6个月的患者，其淋巴组织中HIV RNA降低的程度尚未确定。我们评估了10名接受茚地那韦（IDV）/齐多夫定（ZDV）/拉米夫定（3TC）、IDV或ZDV/3TC治疗36 - 52周的HIV感染受试者血液和腹股沟淋巴结活检组织中的HIV RNA和DNA水平，并对耐药突变进行了特征分析。治疗1年后，个体淋巴结中的病毒RNA水平仍可检测到，但比接受三联药物治疗且中断治疗的受试者或仅接受ZDV/3TC治疗的受试者低log10 = 4，后两者淋巴结中的病毒载量与未治疗患者预期的病毒载量无差异。在所有病例中，淋巴结和外周血单个核细胞（PBMC）中均可检测到病毒DNA。当血浆病毒抑制不完全时，淋巴结和PBMC培养呈阳性且出现耐药。这些研究表明，强效抗逆转录病毒联合治疗显著且持续地抑制血浆病毒血症与治疗1年后淋巴结中低HIV RNA水平相关。相反，治疗1年后即使血浆病毒水平适度持续存在，也反映出病毒持续复制、耐药性的出现以及淋巴结中高病毒载量的维持。
