Seminal HIV-1 Shedding and Drug Resistance in HIV-1/HSV-2 Coinfected Men on HAART

随着高效抗逆转录病毒疗法（HAART）越来越多地用于治疗艾滋病， HIV-1的耐药菌株正在出现，需要使用更新、更昂贵的 药物，往往导致治疗失败。性传播感染（STIs）与 精液中的HIV-1水平升高，可能是由于生殖道中的HIV-1复制促进， 炎性细胞因子，其由STI上调，或由HIV-1基因表达的直接影响， 病原体本身一种高度流行的性传播感染，生殖器单纯疱疹病毒2型（HSV-2）感染， 与生殖器分泌物中HIV-1水平增加和HIV-1性传播率增加有关。 传输目前正在进行临床试验，以确定是否抑制HSV-2感染 与阿昔洛韦的联合应用会影响HIV-1的感染率和传播率。迄今为止，关于HSV-2/HIV相互作用的研究 都集中在未接受过抗逆转录病毒治疗的人群身上。本研究的主要目的是确定疱疹是否 接受HAART治疗的HIV-1感染男性中的单纯疱疹病毒2型（HSV-2）合并感染促进了 生殖道和性传播耐药HIV-1的演变。 接受HAART治疗的临床稳定的HIV-1感染男性将接受HSV-2抗体检测，并入选 比较HSV-2合并感染者精液和血液中HIV-1 RNA和DNA水平的横断面研究 vs. HSV-2未感染男性（n=125例男性/组）。将在HSV-2/HIV-1中进行纵向研究 共感染组，以确定是否肛门生殖器HSV-2再激活（临床症状和/或生殖器HSV 脱落）与HIV-1的生殖器脱落增加有关。RTI和PI药物的频率 将由TRUGENE确定生殖器和配对血液样本中HIV-1 RNA的耐药突变。 我们还将研究精液中HSV-2 DNA和HIV-1 RNA水平是否与 浓度的精液炎症和免疫因子（细胞因子，抗体，白细胞和 其他先天免疫介质）。这项研究将提供有价值的信息， HAART患者生殖器HSV-2和HIV-1感染之间的相互作用， 关于向艾滋病毒感染者提供抗逆转录病毒治疗的公共卫生政策的影响 伴随性传播感染患病率高的人群。

As highly active antiretroviral therapy (HAART) becomes increasingly available for the treatment of HIVdisease, drug resistant strains of HIV-1 are emerging that necessitate the use of newer, more expensive drugs, and often result in treatment failure. Sexually transmitted infections (STIs) have been associated with elevated HIV-1 levels in semen, presumably due to promotion of HIV-1 replication in the genital tract by inflammatory cytokines which are upregulated by STIs, or by direct effects on HIV-1 gene expression by the pathogens themselves. A highly prevalent STI, genital Herpes Simplex Virus 2 (HSV-2) infection, has been associated with increased levels of HIV-1 in genital secretions and an increased rate of HIV-1 sexual transmission. Clinical trials are currently underway to determine whether suppression of HSV-2 infection with acyclovir impacts HIV-1 acquisition and transmission rates. To date, studies on HSV-2/HIV interactions have focused on ART-naive populations. The primary objective of this study is to determine whether Herpes Simplex Virus 2 (HSV-2) co-infection in HIV-1 infected men on HAART promotes HIV replication in the genital tract and the evolution of sexually-transmissible drug-resistant HIV-1. Clinically stable HIV-1 infected men on HAART will be tested for HSV-2 antibodies and enrolled into a cross-sectional study to compare levels of HIV-1 RNA and DNA in semen and blood of HSV-2 co-infected vs. HSV-2 uninfected men (n=125 men/group). A longitudinal study will be conducted in the HSV-2/HIV-1 co-infected group to determine whether anogenital HSV-2 reactivation (clinical symptoms and/or genital HSV shedding) is associated with increased genital shedding of HIV-1. The frequency of RTI and PI drug resistance mutations in HIV-1 RNA from genital and paired blood samples will be determined by TRUGENE. We will also investigate whether seminal HSV-2 DNA and HIV-1 RNA levels are correlated with concentrations of seminal inflammatory and immunological factors (cytokines, antibodies, leukocytes and other mediators of innate immunity). This study will provide valuable information concerning potential interactions between genital HSV-2 and HIV-1 infections in HAART patients, and could have important implications for public health policy regarding provision of antiretroviral therapy to HIV-infected persons in populations with a high prevalence of concomitant STIs.