Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
BMC Infect Dis. 2018 Jun 25;18(1):285. doi: 10.1186/s12879-018-3198-2.
Triple-drug regimens are the gold standard for HIV therapy. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) reducing regimens are used to decrease drugs toxicity, exposure and costs. Aim of our study was to evaluate trends of biochemical and inflammatory indices in patients switching to dual therapy (DT).
We included patients that a) switched to a DT from 2007 to 2015 from a tenofovir/abacavir-based triple regimen b) previously maintained a triple and c) subsequently a dual regimen for 12 months with virological suppression. We retrieved data measured at 5 points (at the switch, 6 and 12 months before and after switch). We used platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and CD4/CD8 ratio as inflammatory indices. We assessed temporal trends of viro-immunological, biochemical and inflammatory parameters.
Overall, 364 and 65 patients switched from a tenofovir- and an abacavir-triple regimen, respectively. In the tenofovir-reducing group, creatinine clearance and lipids raised after the switch. There was a significant increase in both CD4+ cells and CD4/CD8. CD8+ cells rose after the switch, while opposite trend was found for PLR. In the abacavir-reducing group total lipids showed a decrease during the first 6 months after the switch and then stabilized. An increase of CD4+ and a decrease of CD8+ cells was observed during the study period, although not statistically significant. While CD4/CD8 remained stable after simplification, PLR decreased significantly after 6 months, then returning to baseline. CD8+ cells increased in the tenofovir-reducing group despite a viro-immunological response. Intriguingly, PLR decreased, maintaining this trend for 12 and 6 months after tenofovir and abacavir interruption respectively.
Increased PLR has been linked to hypercholesterolemia and metabolic-syndrome, while high CD8+ cells count to increased risk of non-AIDS-related events regardless of CD4 T-cell recovery and to virological failure. Whether these findings may have clinical implications, and which role DT plays on the immune system and on inflammation should be further investigated.
三药方案是 HIV 治疗的金标准。核苷（酸）逆转录酶抑制剂（NRTIs）降低方案用于降低药物毒性、暴露和成本。我们研究的目的是评估转换为双重治疗（DT）的患者的生化和炎症指标的趋势。
我们纳入了以下患者：a）从 2007 年到 2015 年，从替诺福韦/阿巴卡韦三联方案转换为二联方案；b）之前维持三联方案；c）随后维持二联方案 12 个月，病毒学抑制。我们检索了在 5 个时间点（转换时、转换前 6 个月和 12 个月以及转换后）测量的数据。我们使用血小板与淋巴细胞比值（PLR）、中性粒细胞与淋巴细胞比值（NLR）和 CD4/CD8 比值作为炎症指标。我们评估了病毒学免疫、生化和炎症参数的时间趋势。
总体而言，有 364 名患者从替诺福韦三联方案和 65 名患者从阿巴卡韦三联方案转换。在替诺福韦降低组中，肌酐清除率和脂质在转换后升高。CD4+细胞和 CD4/CD8 比值显著增加。CD8+细胞在转换后升高，而 PLR 则呈现相反的趋势。在阿巴卡韦降低组中，总脂质在转换后的前 6 个月内下降，然后稳定下来。在研究期间，观察到 CD4+细胞增加和 CD8+细胞减少，尽管没有统计学意义。虽然 CD4/CD8 在简化后保持稳定，但 PLR 在 6 个月后显著下降，然后恢复到基线。尽管病毒免疫反应增强，但在替诺福韦降低组中 CD8+细胞仍增加。有趣的是，PLR 下降，在替诺福韦和阿巴卡韦中断后分别保持 12 个月和 6 个月的趋势。
PLR 升高与高胆固醇血症和代谢综合征有关，而 CD8+细胞计数升高与非艾滋病相关事件的风险增加有关，无论 CD4 T 细胞恢复和病毒学失败如何。这些发现是否具有临床意义，以及 DT 在免疫系统和炎症中发挥的作用，应进一步研究。
