Seminal plasma HIV-1 RNA concentration is strongly associated with altered levels of seminal plasma interferon-γ, interleukin-17, and interleukin-5

Abstract

Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log10 copies/ml (IQR 2.98, 4.70) and 2.96 log10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level (p<0.0001) was most strongly associated with seminal plasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-γ (p=0.03) and interleukin (IL)-17 (p=0.03) and negatively associated with IL-5 (p=0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-γ and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission.

FIG. 1.

Reproducibility of serial HIV-1 RNA measurements in blood and seminal plasma and relationship of blood and seminal plasma HIV-1 RNA concentrations in a validation cohort of 11 HIV-1 infected men off antiretroviral therapy (ART). Concentrations of HIV-1 RNA from serial measurements utilizing the assay optimization cohort are plotted. Undetectable values (<1.7 log10 RNA copies/ml) were assigned a value of 1.7 log10 RNA copies/ml. (A) The mean values for seminal plasma HIV-1 RNA concentrations (log10 RNA copies/ml) across two visits for each person in the assay optimization cohort are plotted. (B) The mean values for blood plasma HIV-1 RNA concentrations (log10 RNA copies/ml) across two visits for each person in the assay optimization cohort are plotted. (C) The correlation between blood and seminal plasma HIV-1 RNA levels was significant (p=0.03).