2168. Reduced T-cell infiltration at site of HSV reactivation in controlled HIV
Session: Poster Abstract Session: HIV: Other Opportunistic Conditions
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • IDWeek poster 10.21.16.pdf (5.9 MB)
  • Background: HSV-2 is one of the cardinal opportunistic infections of HIV/AIDS and has been shown to increase rates of transmission and acquisition of HIV in serodiscordant partners. While antiviral therapy of HSV-2 does not reduce HIV transmission, treatment of HIV can reduce shedding and symptomatic reactivation of HSV-2. HSV-2 is known to induce a persistent CD4+ and CD8+ T-cell response at the site of reactivation in the genital tissues, which is thought to contribute to viral control. This has not been studied in co-infection with HIV. Here we look at the immune response in genital skin during ulcerative HSV-2 recurrence in HIV-infected and HIV-uninfected individuals by IHC.

    Methods: HIV-infected and uninfected subjects with recurrent HSV-2 genital lesions underwent 5 serial biopsies – at the time of an active lesion, at healing of the lesion, and at the same site 2 and 8 weeks after healing of the lesion. Lesional biopsies were primarily taken from the buttock and perirectal areas in both groups. A control biopsy was taken from a distant site, typically the arm. 8mm slides were prepared, fixed and stained for CD4+ and CD8+ T cells. T cells were enumerated and unpaired t tests (without assumption of equal variances) were performed using STATA version 14.0. P-values <0.05 were considered significant.

    Results: Of the 8 HIV-infected subjects, 7 were on combination antiretroviral (cART) therapy and only 2 had detectable viremia by PCR. The median peripheral blood CD4+ T cell count was 342 (range 167 – 990). On average, the CD4+ T-cell density in biopsy specimens at the time of the lesion was significantly lower in the HIV-infected than HIV-uninfected subjects (145 and 630 cells/mm2, respectively, p-value <0.01), as well as at healing (70 and 381 cells/mm2, p-value 0.02). The mean CD8+ T-cell count in the tissue among HIV-infected and uninfected subjects at the time of the lesion and healing was not significantly different. The ratio between tissue CD4+ and CD8+ T cells in HIV-infected subjects was 0.10-0.63 at the time of the lesion, as compared to 0.70-4.6 in HIV-uninfected subjects.

    Conclusion: Even in individuals with well-treated HIV infection there was an altered T-cell response to local HSV infection, both in the number of tissue-infiltrating CD4+ T cells as well as the balance between CD4+ and CD8+ T-cell subsets.

    Emily Ford, MD1,2, Jia Zhu, PhD1,2, Anna Wald, MD, MPH, FIDSA1,2 and Lawrence Corey, MD, FIDSA1,2, (1)University of Washington, Seattle, WA, (2)Fred Hutchinson Cancer Research Center, Seattle, WA

    Disclosures:

    E. Ford, None

    J. Zhu, None

    A. Wald, None

    L. Corey, None

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