title: 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.
authors.affiliation: 1 Department of Medicine and UCLA AIDS Institute, David Geffen School of Medicine at University of California Los Angeles , Los Angeles, California.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Hoffman
authors.forename: Peter A
authors.initials: PA
authors.lastname: Anton
authors.forename: Gayle Cocita
authors.initials: GC
authors.lastname: Baldwin
authors.forename: Julie
authors.initials: J
authors.lastname: Elliott
authors.forename: Deborah
authors.initials: D
authors.lastname: Anisman-Posner
authors.forename: Karen
authors.initials: K
authors.lastname: Tanner
authors.forename: Tristan
authors.initials: T
authors.lastname: Grogan
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Catherine
authors.initials: C
authors.lastname: Sugar
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Risa M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D020381:Interleukin-17 / Q000032:analysis*; D015848:Interleukin-5 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis*; D012661:Semen / Q000821:virology*; D013223:Statistics as Topic; D019562:Viral Load
chemical_list: C508599:IL5 protein, human; D020381:Interleukin-17; D015848:Interleukin-5; D012367:RNA, Viral; D007371:Interferon-gamma