Experimental Infection withHaemophilus ducreyiin Persons Who Are Infected with HIV Does Not Cause Local or Augment Systemic Viral Replication

Autor: Paul Racz, Carol T. Schnizlein-Bick, James Campbell, Kate R. Fortney, David D. Ho, Klara Tenner-Racz, Diane M. Janowicz, Stanley M. Spinola, Beth Zwickl, Barry P. Katz, Tricia L. Humphreys
Rok vydání: 2007
Předmět:
Zdroj: The Journal of Infectious Diseases. 195:1443-1451
ISSN: 1537-6613
0022-1899
DOI: 10.1086/513877
Popis: Haemophilus ducreyi causes the genital ulcer disease (GUD) chancroid. Chancroid remains prevalent in developing countries, where HIV infection is endemic [1], and facilitates HIV acquisition and transmission [1, 2]. HIV RNA level, or viral load (VL), in the urogenital compartment or its surrogate, plasma VL, is the major predictor of the sexual transmission of HIV [3]. VL is highest during acute HIV infection, during the late stages of AIDS, and during coinfections with other sexually transmitted pathogens [3]. Chancroid is estimated to increase the risk of HIV acquisition by 25-fold [4]. Simulation models estimate that ~80%–90% of the HIV infections that occurred during the first decade of the pandemic in sub-Saharan Africa were mostly attributable to ulcerative sexually transmitted diseases [4, 5]. Men with HIV infection, nongonococcal urethritis (NGU), and GUD in a country in which chancroid is endemic have increased semen VLs versus men with NGU but no GUD, and semen VLs are reduced with appropriate antibiotic therapy for NGU and GUD [6]. However, no prospective studies have examined the effect of chancroid on VL. To study the biology of H. ducreyi, we developed a model in which bacteria are delivered to the skin of the upper arms of healthy adult volunteers by puncture wound [7]. Experimental infection closely mimics the initial stages and histopathology of natural chancroid [7–12]. In the human infection model, H. ducreyi colocalizes with polymorphonuclear neutrophils (PMNs), macrophages, and fibrin [13]; remains extracellular; and evades phagocytosis [14]. These relationships are maintained in natural ulcers [15]. Although atypical presentations of chancroid in HIV-infected persons were initially reported [16, 17], subsequent studies have shown little difference in the clinical course and response to antibiotics between HIV-infected and HIV-seronegativepersons [18–20]. The histopathology of chancroid in HIV-infected and HIV-seronegative persons is similar [11, 21]. We reasoned that experimental infection of HIV-infected volunteers would be safe because the organism is extracellular and impaired T cell–mediated immunity should not have a major effect on the course of experimental infection. Here, we studied interactions between H. ducreyi and HIV by experimentally infecting HIV-infected volunteers with H. ducreyi. We hypothesized that the clinical course and lesional infiltrate in HIV-infected persons would be similar to that seen in HIV-seronegative persons. Because experimental infection in HIV-seronegative persons does not cause systemic immune responses [8], we hypothesized that experimental infection would not lead to sustained increases in HIV replication or the lowering of CD4+ cell counts in the systemic compartment. We also hypothesized that experimental infection would recruit latently infected CD45RO+CD4+ cells and macrophages to the skin, activate these cells, and cause them to produce virus locally in treatment-naive subjects but not in subjects receiving highly active antiretroviral therapy (HAART). This is the first study to prospectively examine the effect of chancroid on HIV replication and CD4+ cell count, albeit in an experimental setting.
Databáze: OpenAIRE
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