Archampong Timothy Na, Boyce Ceejay L, Lartey Margaret, Sagoe Kwamena W, Obo-Akwa Adjoa, Kenu Ernest, Blackard Jason T, Kwara Awewura
Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana.
Korle-Bu Teaching Hospital, Accra, Ghana.
Antivir Ther. 2017;22(1):13-20. doi: 10.3851/IMP3055. Epub 2016 May 11.
The presence of HBV resistance mutations upon initiation or during antiretroviral therapy (ART) in HIV-coinfected patients is an important determinant of treatment response. The main objective of the study was to determine the prevalence of HBV resistance mutations in antiretroviral treatment-naive and treatment-experienced HBV-HIV-coinfected Ghanaian patients with detectable HBV viraemia.
HBV-HIV-coinfected patients who were ART-naive or had received at least 9 months of lamivudine (3TC)-containing ART were enrolled in a cross-sectional study. Demographic and clinical data were collected and HBV DNA quantified. Partial HBV sequences were amplified by PCR and sequenced bi-directionally to obtain a 2.1-2.2 kb fragment for phylogenetic analysis of HBV genotypes and evaluation of drug resistance mutations.
Of the 100 HBV-HIV-coinfected study patients, 75 were successfully PCR-amplified, and 63 were successfully sequenced. Of these 63 patients, 27 (42.9%) were ART-experienced and 58 (92.1%) had HBV genotype E. No resistance mutations were observed in the 36 ART-naive patients, while 21 (77.8%) of 27 treatment-experienced patients had resistance mutations. All patients with resistance mutations had no tenofovir in their regimens, and 80% of them had HIV RNA <40 copies/ml. The 3TC resistance mutations rtL180M and rtM204V were observed in 10 (47.6%) of the 21 patients, while 5 patients (23.8%) had rtV173L, rtL180M and rtM204V mutations.
A high proportion of HBV-HIV-coinfected patients with detectable viraemia on 3TC-containing ART had resistance mutations despite good ART adherence as determined by HIV RNA suppression. This study emphasizes the need for dual therapy as part of a fully suppressive ART in all HBV-HIV-coinfected patients in Ghana.
在合并感染HIV的患者开始抗逆转录病毒治疗(ART)时或治疗期间,乙肝病毒(HBV)耐药突变的存在是治疗反应的一个重要决定因素。该研究的主要目的是确定在未接受过抗逆转录病毒治疗以及有过治疗经历、可检测到HBV病毒血症的合并感染HBV和HIV的加纳患者中HBV耐药突变的流行情况。
未接受过ART或接受过至少9个月含拉米夫定(3TC)ART的合并感染HBV和HIV的患者被纳入一项横断面研究。收集人口统计学和临床数据,并对HBV DNA进行定量。通过聚合酶链反应(PCR)扩增部分HBV序列,并进行双向测序以获得一个2.1 - 2.2 kb的片段,用于HBV基因型的系统发育分析和耐药突变评估。
在100例合并感染HBV和HIV的研究患者中,75例成功进行了PCR扩增,63例成功测序。在这63例患者中,27例(42.9%)有过ART治疗经历,58例(92.1%)为HBV基因型E。在36例未接受过ART的患者中未观察到耐药突变,而在27例有过治疗经历的患者中,21例(77.8%)有耐药突变。所有有耐药突变的患者治疗方案中均未使用替诺福韦,其中80%的患者HIV RNA<40拷贝/ml。在21例患者中的10例(47.6%)观察到3TC耐药突变rtL180M和rtM204V,而5例患者(23.8%)有rtV173L、rtL180M和rtM204V突变。
尽管通过HIV RNA抑制确定ART依从性良好,但在接受含3TC的ART且可检测到病毒血症的合并感染HBV和HIV的患者中,很大一部分存在耐药突变。本研究强调在加纳所有合并感染HBV和HIV的患者中,需要采用双重治疗作为完全抑制性ART的一部分。