Bedimo Roger, Kang Minhee, Tebas Pablo, Overton Edgar T, Hollabaugh Kimberly, McComsey Grace, Bhattacharya Debika, Evans Christopher, Brown Todd T, Taiwo Babafemi
1 VA North Texas , Dallas, Texas.
2 Harvard School of Public Health , Cambridge, Massachusetts.
AIDS Res Hum Retroviruses. 2016 Apr;32(4):325-8. doi: 10.1089/AID.2015.0204. Epub 2015 Nov 24.
HIV/hepatitis C virus (HCV) patients have a 3-fold increased fracture incidence compared to uninfected patients. The impact of HCV therapy on bone health is unclear. We evaluated bone turnover markers (BTM) in well-controlled (HIV RNA <50 copies/ml) HIV/HCV-coinfected patients who received pegylated interferon-α and ribavirin (PEG-IFN/RBV) in ACTG trial A5178. Early virologic responders (EVR: ≥2 log HCV RNA drop at week 12) continued PEG-IFN/RBV and non-EVRs were randomized to continuation of PEG-IFN alone or observation. We assessed changes in C-terminal telopeptide of type 1 collagen (CTX; bone resorption marker) and procollagen type I intact N-terminal propeptide (P1NP; bone formation marker), and whether BTM changes were associated with EVR, complete early virologic response (cEVR: HCV RNA <600 IU/ml at week 12), or PEG-IFN treatment. A total of 192 subjects were included. After 12 weeks of PEG-IFN/RBV, CTX and P1NP decreased: -120 pg/ml and -8.48 μg/liter, respectively (both p < 0.0001). CTX declines were greater in cEVR (N = 91; vs. non-cEVR (N = 101; p = 0.003). From week 12 to 24, CTX declines were sustained among EVR patients who continued PEG-IFN/RBV (p = 0.027 vs. non-EVR) and among non-EVR patients who continued PEG-IFN alone (p = 0.022 vs. Observation). Median decreases of P1NP in EVR vs. non-EVR were similar at weeks 12 and 24. PEG-IFN-based therapy for chronic HCV markedly reduces bone turnover. It is unclear whether this is a direct IFN effect or a result of HCV viral clearance, or whether they will result in improved bone mineral density. Further studies with IFN-free regimens should explore these questions.
与未感染的患者相比，感染人类免疫缺陷病毒/丙型肝炎病毒（HIV/HCV）的患者骨折发生率增加了两倍。HCV治疗对骨骼健康的影响尚不清楚。在ACTG试验A5178中，我们评估了接受聚乙二醇化干扰素-α和利巴韦林（PEG-IFN/RBV）治疗且病情得到良好控制（HIV RNA<50拷贝/ml）的HIV/HCV合并感染患者的骨转换标志物（BTM）。早期病毒学应答者（EVR：第12周时HCV RNA下降≥2 log）继续接受PEG-IFN/RBV治疗，非EVR患者被随机分为继续单独使用PEG-IFN或观察。我们评估了1型胶原C末端肽（CTX；骨吸收标志物）和I型前胶原完整N末端前肽（P1NP；骨形成标志物）的变化，以及BTM变化是否与EVR、完全早期病毒学应答（cEVR：第12周时HCV RNA<600 IU/ml）或PEG-IFN治疗相关。共纳入192名受试者。PEG-IFN/RBV治疗12周后，CTX和P1NP下降：分别下降-120 pg/ml和-8.48 μg/升（均p<0.0001）。cEVR患者（N=91）的CTX下降幅度大于非cEVR患者（N=101；p=0.003）。从第12周到24周，继续接受PEG-IFN/RBV治疗的EVR患者（与非EVR患者相比，p=0.027）以及继续单独接受PEG-IFN治疗的非EVR患者（与观察相比，p=0.022）的CTX持续下降。EVR组与非EVR组在第12周和24周时P1NP的中位数下降相似。基于PEG-IFN的慢性HCV治疗可显著降低骨转换。目前尚不清楚这是IFN的直接作用还是HCV病毒清除的结果，也不清楚它们是否会导致骨矿物质密度改善。使用无IFN方案的进一步研究应探讨这些问题。
