Boyd Anders, Moh Raoul, Gabillard Delphine, le Carrou Jérôme, Danel Christine, Anglaret Xavier, Eholié Serge P, Maylin Sarah, Delaugerre Constance, Zoulim Fabien, Girard Pierre-Marie, Lacombe Karine
INSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
Antivir Ther. 2015;20(6):643-54. doi: 10.3851/IMP2959. Epub 2015 Apr 8.
In HIV-HBV-coinfected patients from sub-Saharan Africa, incidence of antiviral resistant HBV-mutations after initiating long-term antiretroviral therapy (ART) has only been evaluated in limited patient populations.
In this nested, prospective cohort study from two randomized controlled trials in Côte d'Ivoire, 168 ART-naive HIV-HBV-coinfected patients, starting lamivudine (LAM, n=82) or tenofovir/emtricitabine (TDF/FTC, n=86) containing ART were included. HBV DNA viral load (VL) was quantified using an in-house assay (detection limit: <12 copies/ml) while pol and preS/S regions of positive samples were sequenced.
At ART-initiation, 39 (23.2%) were hepatitis B e antigen-positive, 53 (31.5%) had alanine or aspartate aminotransferase levels >40 IU/ml and 98/100 (98.0%) harboured genotype E. Among the 127 (75.6%) patients with detectable baseline HBV VL (median 4.27 log10 copies/ml, IQR 3.14-7.64), cumulative percentage achieving undetectable HBV DNA was 74.2% for patients undergoing LAM-containing ART and 94.2% for TDF/FTC-containing ART after a median 35.5 months (IQR 24.3-36.5). No baseline antiviral resistance mutations were observed. Among 28/127 (22.1%) patients with low-level persistent viraemia (last HBV VL: between 12 to <10(5) copies/ml), no incident amino acid changes associated with antiviral resistance were observed. Among 11/127 (8.7%) patients with high-level persistent viraemia (last HBV VL: ≥10(5) copies/ml), only two harboured incident LAM-resistance mutations at positions rtV173L+rtL180M+rtM204V with no patient exhibiting TDF/FTC-resistance. Two patients had transaminase flares >120 IU/ml (incidence rate =0.5/100 person-years).
Antiviral resistance, particularly to LAM, was remarkably rare in this cohort of HIV-HBV-coinfected patients. Further research is needed to determine which coinfected populations might benefit from LAM-containing ART with low risk of resistance.
在撒哈拉以南非洲地区的HIV-HBV合并感染患者中，启动长期抗逆转录病毒治疗（ART）后抗病毒耐药性HBV突变的发生率仅在有限的患者群体中进行了评估。
在这项来自科特迪瓦的两项随机对照试验的嵌套前瞻性队列研究中，纳入了168例未接受过ART的HIV-HBV合并感染患者，他们开始接受含拉米夫定（LAM，n = 82）或替诺福韦/恩曲他滨（TDF/FTC，n = 86）的ART治疗。使用内部检测方法（检测限：<12拷贝/ml）对HBV DNA病毒载量（VL）进行定量，同时对阳性样本的pol和preS/S区域进行测序。
在开始ART时，39例（23.2%）为乙肝e抗原阳性，53例（31.5%）丙氨酸或天冬氨酸转氨酶水平>40 IU/ml，100例中的98例（98.0%）携带E基因型。在127例（75.6%）基线HBV VL可检测的患者中（中位数为4.27 log10拷贝/ml，IQR为3.14 - 7.64），接受含LAM的ART治疗的患者在中位35.5个月（IQR为24.3 - 36.5）后，实现HBV DNA不可检测的累积百分比为74.2%，接受含TDF/FTC的ART治疗的患者为94.2%。未观察到基线抗病毒耐药突变。在28例（22.1%）低水平持续病毒血症患者中（最后一次HBV VL：介于12至<10⁵拷贝/ml之间），未观察到与抗病毒耐药相关的氨基酸变化。在11例（8.7%）高水平持续病毒血症患者中（最后一次HBV VL：≥10⁵拷贝/ml），只有2例携带rtV173L + rtL180M + rtM204V位点的LAM耐药突变，没有患者表现出TDF/FTC耐药。2例患者转氨酶突然升高>120 IU/ml（发病率=0.5/100人年）。
在这个HIV-HBV合并感染患者队列中，抗病毒耐药，尤其是对LAM的耐药非常罕见。需要进一步研究以确定哪些合并感染人群可能从耐药风险低的含LAM的ART治疗中获益。
