Depletion of CD4+ T cells in semen during HIV infection and their restoration following antiretroviral therapy

Abstract

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 x 10 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.

Figures

Figure 1

Notched box plots representing CD4+ T lymphocyte concentrations in semen of HIV− men and HIV+ men with peripheral blood CD4+ cell counts ≥ and < 500/mm3. For each box, the horizontal lines, from bottom to top, represent 25th, 50th (median) and 75th percentiles, the whiskers delineate the 10th and 90th percentiles, the notch defines the 95% confidence interval around the median and the open circles identify outlying values. Statistically significant group comparisons: HIV− vs. HIV+ ≥ 500/mm3 (p=0.0017) and HIV− vs. HIV+ < 500/mm3 (p=0.0001).