Elvstam Olof, Medstrand Patrik, Yilmaz Aylin, Isberg Per-Erik, Gisslén Magnus, Björkman Per
Department of Translational Medicine, Clinical Infection Medicine Unit, Lund University, Malmö, Sweden.
Department of Translational Medicine, Clinical Virology, Lund University, Malmö, Sweden.
PLoS One. 2017 Jul 6;12(7):e0180761. doi: 10.1371/journal.pone.0180761. eCollection 2017.
Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.
HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL) was calculated in a similar manner.
LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200-999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01]), whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years). LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05) and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09).
In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.
尽管大多数感染HIV的个体在抗逆转录病毒治疗(ART)期间实现了病毒血症检测不到,但仍有一部分人存在持续时间和程度各异的低水平病毒血症(LLV)。LLV对治疗结果的影响尚不清楚。我们调查了瑞典接受ART治疗的患者中LLV与病毒学失败和/或全因死亡率之间的关联。
从全国性登记处InfCare HIV中识别出两个瑞典HIV中心的HIV感染患者。年龄≥15岁且接受三联药物ART治疗的受试者在治疗开始12个月后纳入研究,前提是有≥2次病毒载量测量结果。此时连续2次HIV RNA值≥1000拷贝/mL的患者被排除。参与者根据病毒血症情况分为四类:病毒血症永久抑制(<50拷贝/mL)、LLV 50 - 199拷贝/mL、LLV 200 - 999拷贝/mL和病毒血症≥1000拷贝/mL。使用生存分析计算所有四类病毒血症与全因死亡之间的关联,将病毒血症作为随时间变化的协变量,以便患者在随访期间可能改变病毒血症类别。以类似方式计算三个较低类别与病毒学失败(≥2次连续测量≥1000拷贝/mL)之间的关联。
在7812人年的随访期间(中位时间6.5年),1015例患者中有70例(6.9%)记录为LLV 50 - 199拷贝/mL,89例(8.8%)记录为LLV 200 - 999拷贝/mL。LLV 200 - 999拷贝/mL与病毒学失败相关(调整后的风险比为3.14 [95%置信区间1.41 - 7.03,p<0.01]),而LLV 50 - 199拷贝/mL则无关联(1.01 [0.34 - 4.31,p = 0.99];中位随访时间4.5年)。LLV 200 - 999拷贝/mL的调整后死亡风险比为2.29(0.98 - 5.32,p = 0.05),LLV 50 - 199拷贝/mL为2.19(0.90 - 5.37,p = 0.09)。
在这个瑞典队列中,ART治疗期间的中位随访时间为4.5年,LLV 200 - 999拷贝/mL与病毒学失败独立相关。LLV患者的全因死亡率较高,尽管在多变量分析中无统计学意义。