Downs Jennifer A, Dupnik Kathryn M, van Dam Govert J, Urassa Mark, Lutonja Peter, Kornelis Dieuwke, de Dood Claudia J, Hoekstra Pytsje, Kanjala Chifundo, Isingo Raphael, Peck Robert N, Lee Myung Hee, Corstjens Paul L A M, Todd Jim, Changalucha John M, Johnson Warren D, Fitzgerald Daniel W
Center for Global Health, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America.
Department of Medicine, Bugando Medical Centre, Mwanza, Tanzania.
PLoS Negl Trop Dis. 2017 Sep 25;11(9):e0005968. doi: 10.1371/journal.pntd.0005968. eCollection 2017 Sep.
Schistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion.
METHODOLOGY/PRINCIPAL FINDINGS: We conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants' consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2-6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3-1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9-4.6] log10 copies/mL versus 3.7 [3.2-4.3], p = 0.017.
CONCLUSIONS/SIGNIFICANCE: We confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites.
全球有2.18亿人感染血吸虫病，其中大多数感染病例在非洲。患病率研究表明，慢性血吸虫病患者感染HIV-1的风险可能更高，且一旦感染，控制HIV-1复制的能力会受损。我们推测：（1）既往血吸虫感染可能会增加感染HIV-1的几率，且这种影响在男性和女性中可能有所不同；（2）在感染HIV-1时患有活动性血吸虫感染的个体对HIV-1的免疫控制可能受损，导致在HIV-1血清转化时HIV-1病毒载量更高。
方法/主要发现：我们在坦桑尼亚一项基于人群的大型HIV-1传播调查中开展了一项巢式病例对照研究。2007年、2010年和2013年对来自七个村庄的成年人群进行了HIV检测，并在征得参与者同意后将干血斑存档以备未来研究之用。该人群中约40%感染曼氏血吸虫，2%感染埃及血吸虫。我们对感染HIV-1者在HIV-1血清转化前后的血斑进行了血吸虫抗原检测。我们还对未感染HIV-1的匹配对照的血斑进行了检测，并计算了血吸虫病患者与这些匹配对照相比感染HIV-1的几率。分析按性别分层。我们比较了73例HIV-1血清转化者和265例对照。感染血吸虫的女性感染HIV-1的几率高于未感染者（调整后的比值比=2.8[1.2 - 6.6]，p = 0.019）。感染血吸虫的男性感染HIV-1的几率没有增加（调整后的比值比=0.7[0.3 - 1.8]，p = 0.42）。我们还比较了2010年在该地区广泛使用抗逆转录病毒疗法之前感染血吸虫病的HIV-1血清转化者与未感染血吸虫病的HIV-1血清转化者在血清转化后血斑中的HIV-1 RNA水平。15例感染血吸虫的HIV-1血清转化者的全血HIV-1 RNA水平中位数显著高于22例未感染血吸虫病者：4.4[3.9 - 4.6]log10拷贝/毫升对3.7[3.2 - 4.3]，p = 0.017。
结论/意义：在曼氏血吸虫流行地区，我们证实既往血吸虫感染会增加女性感染HIV-1的几率，并在HIV-1血清转化时提高HIV-1病毒载量。这是第一项证明血吸虫感染对HIV-1易感性和病毒控制的影响，并按性别区分影响的研究。还需要在其他地点进行验证研究。
