Seminari Elena, Tinelli Carmine, Ravasi Giovanni, Ripamonti Diego, Ladisa Nicoletta, Marino Nicoletta, Sighinolfi Laura, Mondello Placido, Migliorino Marco, Carosi Giampiero, Maserati Renato
Servizio Biometria ed Epidemiologia Clinica - Direzione Scientifica - Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
Curr HIV Res. 2010 Apr;8(3):186-93. doi: 10.2174/157016210791111070.
The primary objective of this study was to investigate the impact of HCV infection and of HCV genotypes on immune restoration in HIV-infected patients on a successful HAART regimen.
Patients from the MASTER Study were included in this current longitudinal study if they met the following criteria: being on any successful HAART, availability of CD4+ cell count and HIV RNA level before starting the suppressive HAART and 12 months after suppressive therapy, availability of HCV antibodies. The primary endpoints of the study were defined as achieving a difference above 100 cell/mmc between CD4+ at baseline and at time of HIV RNA suppression while on therapy (DeltaCD4+early), or 12 month after a suppressive therapy (DeltaCD4+late).
844 HIV-positive patients were included in the analysis: 673 were HCV-negative and 171 were HCV-positive [92 (53.8%) subjects had HCV genotype 1; 58 (33.9%), genotype 3; 21 (12.3%), genotype 4]. Plasma HIV RNA (both baseline as highest value), nadir CD4+, being naïve, time to reach undetectable plasma HIV RNA, treatment with PI vs NNRTI were associated with an early immunological recovery; the occurrence of previous AIDS event, a history of injection drug use, and HCV infection were associated with failure to achieve an early immunological recovery. Variables associated with DeltaCD4+late immune recovery were baseline CD4+ value, plasma HIV RNA (both baseline as highest value), being naïve and time to reach undetectable plasma HIV RNA. HCV infection per se was not associated with a worse probability to reach late immunologic response, although among HCV infected patients, having a genotype 3 was associated with a worse immune recovery. At multivariable analysis, factors that remained associated with failure to achieve an early immunological response were being HCV infected and history of injection drug use, while those associated with a failure to achieve a late immunological response were being infected with HCV genotype 3 and older age.
A blunted early immune recovery was observed in HCV infected patients, compared with HCV negative subjects, while late immune recovery was not different among HCV infected as a whole and not infected subjects; only the subgroup of subjects infected with genotype 3 showed an impaired late immune recovery.
本研究的主要目的是调查丙型肝炎病毒（HCV）感染及HCV基因型对接受成功高效抗逆转录病毒治疗（HAART）方案的HIV感染患者免疫恢复的影响。
如果来自MASTER研究的患者符合以下标准，则纳入本纵向研究：正在接受任何成功的HAART治疗，在开始抑制性HAART治疗前及抑制性治疗12个月后可获得CD4 +细胞计数和HIV RNA水平，可获得HCV抗体。该研究的主要终点定义为在治疗期间（早期CD4 +变化量）或抑制性治疗12个月后（晚期CD4 +变化量），基线时与HIV RNA抑制时的CD4 +细胞计数差值超过100个细胞/mm³。
844例HIV阳性患者纳入分析：673例HCV阴性，171例HCV阳性[92例（53.8%）受试者为HCV基因型1；58例（33.9%）为基因型3；21例（12.3%）为基因型4]。血浆HIV RNA（基线值及最高值）、最低CD4 +细胞计数、初治状态、达到不可检测血浆HIV RNA的时间、蛋白酶抑制剂（PI）与非核苷类逆转录酶抑制剂（NNRTI）治疗与早期免疫恢复相关；既往艾滋病事件的发生、注射吸毒史和HCV感染与早期免疫恢复未实现相关。与晚期CD4 +变化量免疫恢复相关的变量为基线CD4 +值、血浆HIV RNA（基线值及最高值）、初治状态和达到不可检测血浆HIV RNA的时间。HCV感染本身与晚期免疫反应较差的可能性无关，尽管在HCV感染患者中，基因型3与免疫恢复较差相关。在多变量分析中，与早期免疫反应未实现相关的因素为HCV感染和注射吸毒史，而与晚期免疫反应未实现相关的因素为感染HCV基因型3和年龄较大。
与HCV阴性受试者相比，HCV感染患者早期免疫恢复减弱，而HCV感染患者整体与未感染受试者的晚期免疫恢复无差异；仅基因型3感染的受试者亚组显示晚期免疫恢复受损。
