Arrigoni Francesca I F, Spyer Moira, Hunter Patricia, Alber Dagmar, Kityo Cissy, Hakim James, Matubu Allen, Olal Patrick, Paton Nicholas I, Walker A Sarah, Klein Nigel
UCL, Great Ormond Street, Institute of Child Health.
Department of Pharmacy, LSPC, HSSCE, Kingston University.
AIDS. 2023 May 1;37(6):913-923. doi: 10.1097/QAD.0000000000003488. Epub 2023 Jan 20.
HIV viral load (VL) monitoring is generally conducted 6-12 monthly in low- and middle-income countries, risking relatively prolonged periods of poor viral control. We explored the effects of different levels of loss of viral control on immune reconstitution and activation.
Two hundred and eight participants starting protease inhibitor (PI)-based second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe were enrolled and CD38 + /HLA-DR + immunophenotyping performed (CD8-FITC/CD38-PE/CD3-PerCP/HLA-DR-APC; centrally gated) in real-time at 0, 12, 48, 96 and 144 weeks from randomization.
VL was assayed retrospectively on samples collected every 12-16 weeks and classified as continuous suppression (<40 copies/ml throughout); suppression with transient blips; low-level rebound (two or more consecutive VL >40, <5000 copies/ml); high-level rebound/nonresponse (two or more consecutive VL >5000 copies/ml).
Immunophenotype reconstitution varied between that defined by numbers of cells and that defined by cell percentages. Furthermore, VL dynamics were associated with substantial differences in expression of CD4 + and CD8 + cell activation markers, with only individuals with high-level rebound/nonresponse (>5000 copies/ml) experiencing significantly greater activation and impaired reconstitution. There was little difference between participants who suppressed consistently and who exhibited transient blips or even low-level rebound by 144 weeks ( P > 0.2 vs. suppressed consistently).
Detectable viral load below the threshold at which WHO guidelines recommend that treatment can be maintained without switching (1000 copies/ml) appear to have at most, small effects on reconstitution and activation, for patients taking a PI-based second-line regimen.
在低收入和中等收入国家，HIV病毒载量（VL）监测通常每6至12个月进行一次，这存在病毒控制不佳的时间相对较长的风险。我们探讨了不同程度的病毒控制丧失对免疫重建和激活的影响。
在乌干达和津巴布韦进行的EARNEST试验（ISRCTN37737787）中，招募了208名开始基于蛋白酶抑制剂（PI）的二线治疗的参与者，并在随机分组后的0、12、48、96和144周实时进行CD38 + /HLA-DR +免疫表型分析（CD8-FITC/CD38-PE/CD3-PerCP/HLA-DR-APC；中心门控）。
对每12至16周收集的样本进行回顾性病毒载量检测，并分类为持续抑制（整个过程中<40拷贝/毫升）；有短暂波动的抑制；低水平反弹（连续两次或更多次病毒载量>40，<5000拷贝/毫升）；高水平反弹/无反应（连续两次或更多次病毒载量>5000拷贝/毫升）。
免疫表型重建在由细胞数量定义的和由细胞百分比定义的之间有所不同。此外，病毒载量动态与CD4 +和CD8 +细胞激活标志物的表达存在显著差异相关，只有高水平反弹/无反应（>5000拷贝/毫升）的个体经历了明显更大的激活和重建受损。到144周时，持续抑制的参与者与出现短暂波动甚至低水平反弹的参与者之间几乎没有差异（与持续抑制相比，P>0.2）。
对于采用基于PI的二线治疗方案的患者，低于世界卫生组织指南推荐的无需换药即可维持治疗的阈值（1000拷贝/毫升）的可检测病毒载量似乎对重建和激活至多有微小影响。
