Department of Pediatrics, Hospital 12 de Octubre, Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre, Madrid, Spain.
Biomedical School, Uiversidad Europea de Madrid, Madrid, Spain.
J Acquir Immune Defic Syndr. 2018 Oct 1;79(2):269-276. doi: 10.1097/QAI.0000000000001789.
Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size.
We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting antiretroviral therapy (ART) <6 months of age.
Total HIV-1 DNA was measured from 51 long-term suppressed children aged 6.3 years (median) after initial viral suppression. Factors associated with log10 total HIV-1 DNA were analyzed using linear regression.
At ART initiation, children were aged median [IQR] 2.3 [1.2-4.1] months, CD4% 37 [24-45] %, CD8% 28 [18-36] %, log10 plasma viral load (VL) 5.4 [4.4-5.9] copies per milliliter. Time to viral suppression was 7.98 [4.6-19.3] months. After suppression, 13 (25%) children had suboptimal response [≥2 consecutive VL 50-400 followed by VL <50] and/or experienced periods of virological failure [≥2 consecutive VL ≥400 followed by VL <50]. Median total HIV-1 DNA was 43 [6195] copies/10 PBMC. Younger age at therapy initiation was associated with lower total HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, P = 0.0091), with a month increase in age at ART start being associated with a 13% increase in HIV DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per 10% higher, P = 0.0022) and the absence of viral failure/suboptimal response (AC 0.34 for those with fail/suboptimal response, P = 0.0483) were associated with lower total HIV-1 DNA.
Early ART initiation and a higher proportion of time suppressed are linked with lower total HIV-1 DNA. Early ART start and improving adherence in perinatally HIV-1-infected children minimize the size of viral reservoir.
未来旨在实现 HIV-1 缓解的策略可能针对的是 reservoir 规模较小的个体。
我们回顾性调查了在开始接受抗逆转录病毒治疗(ART)<6 个月的欧洲围产期 HIV 感染儿童中,与 HIV-1 DNA 水平相关的因素。
从 51 名长期抑制的儿童中测量了总 HIV-1 DNA,这些儿童在初始病毒抑制后年龄为 6.3 岁(中位数)。使用线性回归分析与 log10 总 HIV-1 DNA 相关的因素。
在开始 ART 时,儿童的年龄中位数(IQR)为 2.3(1.2-4.1)个月,CD4%为 37(24-45)%,CD8%为 28(18-36)%,log10 血浆病毒载量(VL)为 5.4(4.4-5.9)拷贝/毫升。病毒抑制的时间为 7.98(4.6-19.3)个月。抑制后,13(25%)名儿童出现了不理想的反应[≥2 次连续 VL 50-400 随后 VL<50]和/或经历了病毒学失败[≥2 次连续 VL≥400 随后 VL<50]。中位总 HIV-1 DNA 为 43[6195]拷贝/10 PBMC。治疗开始时年龄较小与总 HIV-1 DNA 较低有关(调整后的系数[AC]为每月增加 0.12 岁,P=0.0091),ART 开始时年龄增加一个月与 HIV DNA 增加 13%有关。同样,更长时间的病毒抑制比例(AC 为每增加 10%的时间增加 0.10,P=0.0022)和无病毒失败/不理想反应(对于有失败/不理想反应的人,AC 为 0.34,P=0.0483)与总 HIV-1 DNA 较低有关。
早期 ART 开始和更长时间的抑制比例与总 HIV-1 DNA 较低有关。围产期 HIV-1 感染儿童的早期 ART 开始和提高依从性可最大限度地减少 reservoir 的大小。