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)越来越多地可用于治疗艾滋病毒疾病， HIV-1的抗药性毒株正在出现，需要使用更新的、更昂贵的 药物，并经常导致治疗失败。性传播感染(STI)与 精液中艾滋病毒-1水平升高，可能是由于促进艾滋病毒-1在生殖道复制 性传播感染或通过直接作用于HIV-1基因表达而上调的炎性细胞因子 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， 生殖器分泌物中HIV-1水平的增加和HIV-1性行为比率的增加 变速箱。目前正在进行临床试验，以确定抑制HSV-2感染 阿昔洛韦对艾滋病毒-1的感染和传播率产生影响。迄今为止，关于HSV-2/HIV相互作用的研究 专注于艺术天真的人群。这项研究的主要目标是确定疱疹病毒 单纯疱疹病毒2型(HSV-2)在接受HAART治疗的HIV-1感染者中的混合感染促进HIV在 生殖道和性传播耐药艾滋病毒-1的演变。 接受HAART治疗的临床稳定的HIV-1感染者将接受HSV-2抗体检测，并参加 单纯疱疹病毒2型混合感染患者精液和血液中HIV-1RNA和DNA水平的比较研究 单纯疱疹病毒2型感染男性(n=125人/组)。将对HSV-2/HIV-1进行纵向研究 联合感染组确定肛门生殖道HSV-2是否重新激活(临床症状和/或生殖器HSV 生殖器脱落)与HIV-1生殖器脱落的增加有关。RTI和PI类药物的使用频率 TRUGENE将确定生殖器和配对血液样本中HIV-1RNA的耐药性突变。 我们还将调查精液中HSV-2DNA和HIV-1RNA水平是否与 精液炎症和免疫因子(细胞因子、抗体、白细胞和 其他先天免疫力的调解人)。这项研究将提供有关潜力的有价值的信息 HAART患者生殖器HSV-2和HIV-1感染之间的相互作用，可能具有重要的意义 年向艾滋病毒感染者提供抗逆转录病毒治疗对公共卫生政策的影响 伴发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.