We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. ...We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, - 3900) copies/mL after 14 (17.9, 0 - 58) months of LLV. Few patients maintained LLV for the entire 9 years period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p = 0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.展开更多
虽然新生儿普遍接种慢性乙型肝炎病毒(hepatitis B virus,HBV)疫苗,HBV的感染率开始大幅下降,但2016年我国慢性HBV感染者仍有8600万例。2019年,全球有2.96亿例慢性HBV感染者,且每年约有82万人死于HBV感染所致的肝衰竭、肝硬化或肝细胞癌...虽然新生儿普遍接种慢性乙型肝炎病毒(hepatitis B virus,HBV)疫苗,HBV的感染率开始大幅下降,但2016年我国慢性HBV感染者仍有8600万例。2019年,全球有2.96亿例慢性HBV感染者,且每年约有82万人死于HBV感染所致的肝衰竭、肝硬化或肝细胞癌(hepatocellular carcinoma,HCC)等相关疾病。多数慢性乙型肝炎患者经恩替卡韦、替诺福韦、丙酚替诺福韦等规范抗病毒治疗后,可以取得抑制病毒复制、延缓疾病进展的疗效。但随着人们对疾病更深层次的认识及检测技术的提升,临床发现部分患者经规范治疗48周后,血清HBV DNA低于2000 IU/mL,但持续或间歇地高于检测下限,即为低病毒血症状态。低病毒血症的发生机制目前尚不明确。相关研究已经表明,HBV低病毒血症影响患者的临床预后,主要表现为促进肝脏炎症、肝纤维化的进展及发生肝硬化失代偿、肝细胞癌、耐药的风险升高。对于HBV低病毒血症患者的治疗方案也尚未有明确建议。本文将对HBV低病毒血症的定义、可能的发生机制、临床意义及临床管理策略等方面进行介绍,为临床医师提供参考。展开更多
文摘We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, - 3900) copies/mL after 14 (17.9, 0 - 58) months of LLV. Few patients maintained LLV for the entire 9 years period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p = 0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.
