Wu Lynne, Kottilil Shyam, Lempicki Richard, Yang Jun, McLaughlin Mary, Hu Zonghui, Koratich Chad, Reitano Kristin N, Rehm Catherine A, Masur Henry, Wood Brad, Kleiner David E, Polis Michael A
Laboratory of Immunoregulation, NIAID, NIH, DHHS, Bethesda, Maryland, USA.
AIDS Res Hum Retroviruses. 2006 Nov;22(11):1091-8. doi: 10.1089/aid.2006.22.1091.
Most HIV/HCV-coinfected patients fail to achieve a sustained virologic response (SVR) to peginterferon-ribavirin therapy. We examined the hepatic histologic response (HR), defined as an improvement in hepatic inflammation scores of two points or more, to combination therapy among HIV/HCV-coinfected subjects. An open label prospective trial treated 32 HIV/HCV-coinfected patients with peginterferon alpha-2b and ribavirin for 48 weeks. Liver biopsies, scored by a single pathologist using the Histology Activity Index (HAI, range 0-18) and Ishak fibrosis scores (range 0-6), were performed before and after treatment. Gene expression profiles of PBMCs were performed using Affymetrix U133A gene chips. A total of 87% of SVR subjects and 88% of nonresponders (NR) had an HR, but no significant change in the liver fibrosis scores was observed (p > 0.05). For genotype 1 patients, a baseline fibrosis score </=2 was related to a higher likelihood of SVR than those with a score >2 (p = 0.012). Combination therapy for HCV among HIV-coinfected subjects resulted in a modest SVR rate. Persons with mild liver disease had a better SVR rate, suggesting early treatment may be beneficial. Combination therapy resulted in an HR for most of the patients, however, further follow-up of these patients will determine the durability of such an HR.
大多数合并感染HIV/HCV的患者接受聚乙二醇干扰素-利巴韦林治疗后未能实现持续病毒学应答(SVR)。我们研究了合并感染HIV/HCV的受试者接受联合治疗后的肝脏组织学应答(HR),定义为肝脏炎症评分改善两分或更多。一项开放标签前瞻性试验对32例合并感染HIV/HCV的患者使用聚乙二醇干扰素α-2b和利巴韦林治疗48周。治疗前后均进行肝脏活检,由一名病理学家使用组织学活动指数(HAI,范围0 - 18)和Ishak纤维化评分(范围0 - 6)进行评分。使用Affymetrix U133A基因芯片对PBMCs进行基因表达谱分析。共有87%的SVR受试者和88%的无应答者(NR)有HR,但未观察到肝脏纤维化评分有显著变化(p>0.05)。对于基因1型患者,基线纤维化评分≤2的患者比评分>2的患者有更高的SVR可能性(p = 0.012)。合并感染HIV的受试者接受HCV联合治疗的SVR率中等。轻度肝病患者的SVR率更高,提示早期治疗可能有益。联合治疗使大多数患者有HR,然而,对这些患者的进一步随访将确定这种HR的持续性。