Depletion of CD4+ T Cells in Semen During HIV Infection and Their Restoration Following Antiretroviral Therapy

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Background:Information concerning the effects of HIV-1 infection, disease progression, and antiretroviral therapy (ART) on male genital white blood cell (WBC) profiles could provide important insight into genital immune defense in HIV-infected men and seminal HIV transmission mechanisms.Objective:To compare concentrations of WBC populations in semen from HIV-1-seronegative (HIV) and HIV-1-seropositive (HIV+) men and determine whether HIV disease stage and ART are associated with alterations in seminal WBC profiles.Subjects and Methods:Subjects were 102 HIV men, 98 ART-naive (ART) HIV+ men, and 22 HIV+ men on dual nucleoside ART, before and 6 months after addition of indinavir. Seminal WBCs, macrophages (MØ), and T-lymphocyte subpopulations were enumerated by immunohistology technique.Results:Seminal CD4+ and CD8+ T-cell populations were severely depleted in most ART HIV+ men regardless of peripheral blood CD4+ cell count. Seminal MØ counts were reduced by 50%. HIV+ men on dual nucleoside ART had significantly higher seminal MØ, CD4+, and CD8+ T-cell counts than ART HIV+ men; addition of indinavir led to a dramatic (>25-fold, P < 0.001) increase in seminal CD4+ T-cell counts which paralleled an increase in blood CD4+ cell counts. Two outlier ART HIV+ men with notably elevated seminal WBC profiles (>20 × 106 WBCs/mL) and infectious cell-associated HIV in semen are described.Conclusions:HIV infection severely depletes CD4+ T cells in the male genital tract as it does at other mucosal sites. This provides evidence that ART HIV+ men have depressed T cell-dependent genital immune defense functions and are vulnerable to other genital infections that could promote HIV transmission. Seminal CD4+ T-cell counts rebounded after treatment with a viral-suppressing ART regimen, indicating that ART may reverse HIV-associated genital immunosuppression. The relative abundance of seminal MØ in HIV+ men suggests that these cells may be predominant HIV host cells in the male genital tract and vectors of HIV transmission. A subgroup of HIV+ men with exceptionally elevated seminal MØ and CD4+ T-cell counts and HIV titers may be highly infectious and contribute disproportionately to HIV transmission.

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