Xiao Hong, Xue Yile, Gu Shiming, Wang Jiangrong, Sun Hongqing, Lu Hongzhou
Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University.
Biosci Trends. 2016 Feb;10(1):42-6. doi: 10.5582/bst.2015.01180. Epub 2016 Feb 24.
When treating HIV-infected patients with hemophilia, adverse drug reactions and interactions and the effect of treatment on bleeding disorders must be considered. Raltegravir is the first HIV integrase inhibitor, but its use in patients with hemophilia is rarely reported. Nine HIV-positive patients with hemophilia were retrospectively studied with a focus on the virological response, changes in the CD4 count, the tendency to bleed, and the response to replacement therapy before and after raltegravir-based antiretroviral therapy (ART). The nine patients were highly treatment-experienced patients and they received raltegravir-based ART for at least nine months. The patients had their own reasons for changing to raltegravir-based ART. During treatment, the CD4 count increased progressively in four patients, with a median absolute increase of 233 cells/mm(3), while the count stabilized in the remaining five patients. Two previous recipients of lopinavir/ritonavir (LPV/r) who failed to respond to lamivudine (3TC) + zidovudine (ZDV) + efavirenz (EFV) had a viral rebound. Genotyping indicated multidrug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). A pattern of resistance to raltegravir was evident, including the primary mutation N155H and the secondary mutation T97A. In the two patients, the tendency to bleed decreased markedly and monthly usage of clotting factor VIII decreased significantly decreased. In the remaining seven patients, the viral load remained < 40 copies/mL, there was no evidence of an increased tendency to bleed, and no evidence of changes in the response to replacement therapy. All of the patients had a stable condition with no signs of disease progression and no serious adverse reactions. Results indicated that Raltegravir-based therapy offered a safe and well-tolerated option for HIV-positive patients with hemophilia.
在治疗感染HIV的血友病患者时，必须考虑药物不良反应及相互作用以及治疗对出血性疾病的影响。雷特格韦是首个HIV整合酶抑制剂，但关于其在血友病患者中的应用报道较少。我们对9例HIV阳性的血友病患者进行了回顾性研究，重点关注基于雷特格韦的抗逆转录病毒疗法（ART）前后的病毒学反应、CD4细胞计数变化、出血倾向以及替代疗法反应。这9例患者均为治疗经验丰富的患者，他们接受基于雷特格韦的ART治疗至少9个月。这些患者更换为基于雷特格韦的ART各有其原因。治疗期间，4例患者的CD4细胞计数逐渐增加，绝对计数中位数增加233个细胞/mm³，而其余5例患者的计数稳定。2例先前接受洛匹那韦/利托那韦（LPV/r）治疗且对拉米夫定（3TC）+齐多夫定（ZDV）+依非韦伦（EFV）无反应的患者出现病毒反弹。基因分型显示对核苷类逆转录酶抑制剂（NRTIs）和非核苷类逆转录酶抑制剂（NNRTIs）存在多药耐药。对雷特格韦的耐药模式明显，包括主要突变N155H和次要突变T97A。在这2例患者中，出血倾向明显降低，凝血因子VIII的每月用量显著减少。在其余7例患者中，病毒载量仍<40拷贝/mL，没有出血倾向增加的证据，也没有替代疗法反应改变的证据。所有患者病情稳定，无疾病进展迹象，也无严重不良反应。结果表明，基于雷特格韦的疗法为HIV阳性的血友病患者提供了一种安全且耐受性良好的选择。
