O'Connor Jemma, Smith Colette, Lampe Fiona, Johnson Margaret, Sabin Caroline, Phillips Andrew
Department of Infection and Population Health, UCL, London, UK.
Ian Charleson Day Centre, Royal Free Hampstead NHS Trust, London, UK.
J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19527. doi: 10.7448/IAS.17.4.19527. eCollection 2014.
Most people achieve and maintain viral load (VL) suppression on first-line antiretroviral therapy (ART) but for a minority this does not happen. It is unclear whether those who have maintained VL suppression for several years will be able to continue to do so, or if rates of VL failure - due to poor adherence, ART interruption and/or resistance - remain at appreciable levels.
Eligible participants were ART-naïve and started treatment after 1st January 2000, with ≥3 antiretrovirals and ≥9 months follow-up. VL failure was defined as failure to achieve VL suppression (≤50 copies/mL) by 9 months on ART or a single VL >200 copies/mL after 9 months after start of ART. Kaplan-Meier estimates were used to examine the cumulative probability of experiencing a VL >200 copies/mL over time, irrespective of treatment interruption (Figure 1). Follow-up was censored at last VL assessment but not at treatment interruption. In a sensitivity analysis, VL failure was instead defined as two consecutive VL >1000 copies/mL.
A total of 13,556 participants were included. Median (IQR) age at start of ART was 37 (32-43), median follow-up 4.1 (2.3-6.7) years, pre-ART VL 71,400 (17,400-221,900) copies/mL and pre-ART CD4 count 204 (110-290) cells/mm(3). Fifty-one percent were white, 71% male and 50% MSM. Of which, 5,351 (39%) participants experienced a VL >200 copies/mL. In sub-groups of participants the proportion experiencing a VL >200 copies/mL by one year after start of ART were: <50 years 22%, ≥50 years 17%, men 20%, women 26%, MSM 19%, black heterosexuals 23%, white heterosexuals 26% and other 23%. The median time to VL >200 copies/ml was 8 years. In sensitivity analyses based on 12,811 participants, 4274 (33%) experienced two consecutive VL >1000 copies/mL. Table 1 presents the rate of experiencing a VL >200 copies/mL (two consecutive VL >1000 copies/mL) by time since start of ART. The rate of VL >200 copies/mL declines over time, from 30 per 100 person-years after up to two years after ART, to two per 100 person-years after up to 11.5 years after ART. A sum of 2,047 (15%) participants stopped ART at some point (10, 14 and 17% had stopped ART by 1, 3, and 5 years, respectively).
Although resistance will often not be present and, even if present, several drug options will likely remain, first occurrence of VL > 200 copies/mL after having attained viral suppression continues to occur after 10 years on ART.
大多数人在一线抗逆转录病毒治疗（ART）中实现并维持病毒载量（VL）抑制，但少数人并非如此。目前尚不清楚那些已经维持数年VL抑制的人是否能够继续保持，或者由于依从性差、ART中断和/或耐药导致的VL失败率是否仍处于相当高的水平。
符合条件的参与者为初治患者，于2000年1月1日后开始治疗，使用≥3种抗逆转录病毒药物，随访≥9个月。VL失败定义为在ART治疗9个月时未实现VL抑制（≤50拷贝/毫升）或在开始ART治疗9个月后单次VL>200拷贝/毫升。采用Kaplan-Meier估计法来研究随时间推移出现VL>200拷贝/毫升的累积概率，无论治疗是否中断（图1）。随访在最后一次VL评估时截尾，但不在治疗中断时截尾。在一项敏感性分析中，VL失败改为定义为连续两次VL>1000拷贝/毫升。
共纳入13556名参与者。ART开始时的中位（IQR）年龄为37岁（32 - 43岁），中位随访时间为4.1年（2.3 - 6.7年），ART治疗前VL为71400（17400 - 221900）拷贝/毫升，ART治疗前CD4细胞计数为204（110 - 290）个/立方毫米。51%为白人，71%为男性，50%为男男性行为者。其中，5351名（39%）参与者出现VL>200拷贝/毫升。在各亚组参与者中，ART开始后1年时出现VL>200拷贝/毫升的比例分别为：<50岁者22%，≥50岁者17%，男性20%，女性26%，男男性行为者19%，黑人异性恋者23%，白人异性恋者26%，其他23%。VL>200拷贝/毫升的中位时间为8年。在基于12811名参与者的敏感性分析中，4274名（33%）出现连续两次VL>1000拷贝/毫升。表1列出了自ART开始以来不同时间出现VL>200拷贝/毫升（连续两次VL>1000拷贝/毫升）的发生率。VL>200拷贝/毫升的发生率随时间下降，从ART开始后两年内每100人年30例降至ART开始后11.5年内每100人年2例。共有2047名（15%）参与者在某个时间点停止了ART（分别有10%、14%和17%在1年、3年和5年后停止了ART）。
尽管通常不会出现耐药，即使出现耐药，可能仍有几种药物选择，但在实现病毒抑制后首次出现VL>200拷贝/毫升的情况在ART治疗10年后仍会发生。
