Nicastri Emanuele, Sarmati Loredana, d'Ettorre Gabriella, Palmisano Lucia, Parisi Saverio G, Uccella Ilaria, Rianda Alessia, Concia Ercole, Vullo Vincenzo, Vella Stefano, Andreoni Massimo
National Institute of Infectious Diseases, IRCCS L. Spallanzani, Rome, Italy.
J Med Virol. 2003 Jan;69(1):1-6. doi: 10.1002/jmv.10269.
The fitness of human immunodeficiency virus (HIV) in vivo depends on the interaction of a multitude of viral and host factors. The aim of this study was to analyze the biological phenotype and the intrinsic capacity of the HIV isolates with drug-resistance mutations to replicate efficiently in the absence of drugs. An open label multicenter cross-sectional study was undertaken on 28 HIV-infected patients failing antiretroviral treatment. The subjects were studied for CD4+ cell count, HIV viral load, syncytium-inducing phenotype, genotypic drug-resistance assay, and replication capacity of HIV isolates assessed by co-culture assay. All HIV isolates showed a decreased replication capacity compared with wild-type strains. The lowest replication capacity was detected in HIV strains with more than five drug-resistance mutations. The highest replication capacity was observed in strains carrying the K103N and Y181C primary mutations that emerged after treatment with non-nucleoside analogue inhibitors. Isolates with R5 biological phenotype had a higher number of resistant mutations than X4 isolates (P = 0.004). Particularly, the R5 phenotype was detected in all 6 isolates with more than 14 drug-resistance mutations. Patients with R5 strains had plasma viral load similar to patients with X4 strains, but marginally higher CD4+ cell counts, and their HIV isolates had significantly lower replication capacity of HIV isolates (P = 0.008). No patient carrying HIV with a maintained replication capacity had a viral load less than 30,000 copies/ml. In patients failing HAART, the detection of HIV isolates with the R5 biological phenotype correlates with CD4+ cell count, an impaired replication capacity, and a high number of drug-resistance mutations.
人类免疫缺陷病毒（HIV）在体内的适应性取决于多种病毒和宿主因素的相互作用。本研究的目的是分析具有耐药突变的HIV分离株在无药物情况下高效复制的生物学表型和内在能力。对28例抗逆转录病毒治疗失败的HIV感染患者进行了一项开放标签多中心横断面研究。对受试者进行了CD4+细胞计数、HIV病毒载量、合胞体诱导表型、基因型耐药性检测以及通过共培养检测评估的HIV分离株复制能力的研究。与野生型毒株相比，所有HIV分离株的复制能力均降低。在具有超过五种耐药突变的HIV毒株中检测到最低的复制能力。在接受非核苷类类似物抑制剂治疗后出现的携带K103N和Y181C主要突变的毒株中观察到最高的复制能力。具有R5生物学表型的分离株比X4分离株具有更多的耐药突变（P = 0.004）。特别是，在所有6例具有超过14种耐药突变的分离株中均检测到R5表型。携带R5毒株的患者血浆病毒载量与携带X4毒株的患者相似，但CD4+细胞计数略高，且其HIV分离株的HIV复制能力明显较低（P = 0.008）。没有携带具有维持复制能力的HIV的患者病毒载量低于30,000拷贝/毫升。在接受高效抗逆转录病毒治疗（HAART）失败的患者中，检测到具有R5生物学表型的HIV分离株与CD4+细胞计数、复制能力受损以及大量耐药突变相关。
