Yap Siew Hwei, Abdullah Noor Kamila, McStea Megan, Takayama Kozo, Chong Meng Li, Crisci Elisa, Larsson Marie, Azwa Iskandar, Kamarulzaman Adeeba, Leong Kok Hoong, Woo Yin Ling, Rajasuriar Reena
Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia.
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
PLoS One. 2017 Oct 9;12(10):e0186000. doi: 10.1371/journal.pone.0186000. eCollection 2017.
Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants.
In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression.
A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation.
Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.
在接受抗逆转录病毒（ART）治疗的人类免疫缺陷病毒（HIV）感染者中，人疱疹病毒（HHV）合并感染与残留的慢性炎症有关。然而，HHV在调节HIV感染者色氨酸-犬尿氨酸途径及临床结局中的作用尚不清楚。因此，我们调查了接受治疗的HIV感染者中四种常见HHV的血清流行率，以及它们对HIV/HHV合并感染者犬尿氨酸/色氨酸（K/T）比值和长期CD4 T细胞恢复的影响。
在这项横断面研究中，从马来西亚马来亚大学医学中心（UMMC）招募了接受至少12个月抑制性ART治疗的HIV感染者。对储存的血浆进行分析，检测巨细胞病毒（CMV）、水痘带状疱疹病毒（VZV）、单纯疱疹病毒1型（HSV-1）和单纯疱疹病毒2型（HSV-2）的IgG抗体水平、免疫激活标志物（白细胞介素-6、干扰素-γ、新蝶呤和可溶性CD14）、犬尿氨酸和色氨酸浓度。使用多变量泊松回归评估HHV合并感染数量和K/T比值对CD4 T细胞恢复的影响。
共招募了232名HIV感染者，所有参与者至少对一种HHV血清学呈阳性；CMV为96.1%，VZV为86.6%，HSV-1为70.7%，HSV-2为53.9%。K/T比值与CMV（rho = 0.205，p = 0.002）、VZV（rho = 0.173，p = 0.009）呈显著正相关，与HSV-2有一定趋势（rho = 0.120，p = 0.070），在SOM分析评估的四种HHV中，CMV抗体滴度对K/T比值的调节作用最强。在多变量分析中，较高的K/T比值（p = ）和增加的HHV合并感染数量（p<0.001）与ART开始12个月后较差的CD4 T细胞恢复独立相关。
在发展中国家环境中，接受ART治疗的HIV感染者中多种HHV合并感染很常见，并与持续的免疫激活和较差的CD4 T细胞恢复有关。 （注：原文中较高的K/T比值处p值缺失）
