Meini Genny, Rossetti Barbara, Bianco Claudia, Ceccherini-Silberstein Francesca, Di Giambenedetto Simona, Sighinolfi Laura, Monno Laura, Castagna Antonella, Rozera Gabriella, D'Arminio Monforte Antonella, Zazzi Maurizio, De Luca Andrea
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
J Antimicrob Chemother. 2014 Mar;69(3):735-41. doi: 10.1093/jac/dkt426. Epub 2013 Oct 23.
Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment.
HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated.
Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing.
HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option.
马拉维若已被证明对携带CCR5嗜性HIV-1的患者有效。虽然这种CCR5拮抗剂最初用于挽救治疗，但其出色的安全性使其成为血浆病毒血症得到抑制的患者抗逆转录病毒治疗简化策略的理想选择。本研究的目的是比较一线治疗前基线血浆RNA和外周血单个核细胞（PBMC）DNA中检测到的HIV-1嗜性，并分析成功治疗期间的嗜性演变。
在42例患者中，采用一式三份的基因分型检测结合基因2表型[共受体]分析，以10%的假阳性率确定HIV-1嗜性。评估配对的治疗前血浆RNA和PBMC DNA以及随后的两个PBMC DNA样本（第一个在血浆HIV-1 RNA检测不到后获得，第二个在血浆病毒血症抑制至少2年后获得）。
共受体嗜性在配对的治疗前RNA和DNA中完全一致，26.2%的HIV-1序列预计为非CCR5嗜性。在随访期间，4例（9.5%）患者检测到共受体嗜性转换，无任何偏好方向。虽然一式三份检测中假阳性率差异很常见，但在这个主要为CCR5嗜性的数据集中，一式三份检测结果中共受体嗜性分配的不一致率仅为2.1%，这对一式三份检测相对于单次检测的附加价值提出了质疑。
在病毒学成功的一线治疗期间，HIV-1共受体嗜性变化很少见。因此，HIV-1 DNA分析可能有助于治疗转换策略中CCR5拮抗剂的选择；然而，需要马拉维若治疗结果数据来证实这一选择。
