Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation

Abstract

Objective To assess the association between CMV IgG antibody levels, HIV disease progression, and immune activation in sub-Saharan Africa. Design A prospective cohort study was conducted among women enrolled in a trial that was designed to determine the effect of acyclovir on HIV disease progression in Rakai, Uganda. Methods The primary endpoints were progression to a CD4+ T-cell count<250 cells/μL, non-traumatic death, or initiation of ART. CD4+ T-cell counts, HIV viral load, C-reactive protein, and soluble CD14 levels were assessed biannually for 24 months. CMV IgG antibody were measured at baseline among all women, and annually among a subset of women who initiated ART during the study. Results There were 300 HIV/CMV coinfected participants who contributed a total of 426.4 person-years with a median follow-up time of 1.81 years. Compared to the lowest CMV IgG tertile group at baseline, the highest CMV IgG tertile group was associated with an increased risk to reach a primary endpoint independent of acyclovir use, age, CD4+ T-cell count, and HIV viral load at baseline (adjHR=1.59;[95%CI=1.05-2.39];P=0.027). Among pre-ART visits (n=1,200), women in the highest baseline CMV IgG tertile had increasing annual rates of sCD14 and CRP levels, which was not observed for the low CMV IgG tertile group. Compared to pre-ART visits, CMV IgG antibody levels were higher post-ART initiation, and concurrent levels remained associated with sCD14 and CRP during suppressive ART (n=95). Conclusion The magnitude of the immune response to CMV was associated with HIV disease progression and immune activation in sub-Saharan Africa.

Preserved immune functionality and high CMV-specific T-cell responses in HIV-infected individuals with poor CD4+ T-cell immune recovery

“…In our study, an association between CMV-specific T-cell response and anti-CMV IgG antibodies was observed with higher level of anti-CMV IgG antibodies in immunodiscordant individuals (Gómez-Mora et al ., PLOS ONE. Accepted Manuscript) and in line with a recent study, where an association between CMV IgG levels and disease progression has been reported 27 . It has been demonstrated that circulating anti-CMV IgG antibodies and CMV-specific T-cell responses are associated with cardiovascular diseases and physical function impairment 23 , 25 , 26 , 43 , suggesting that in HIV + individuals with poor CD4 + T-cell recovery the high CMV-specific response, probably due to episodes of CMV reactivation mainly in the genital tract 41 , 44 , may have an impact in the higher mortality and morbidity observed in those individuals.…”

“…In particular, CMV has been described as a major contributor to the increased immune activation and senescence in HIV + individuals with poor CD4 + T-cell recovery 20 – 22 . Furthermore, increased CMV-specific antibodies and/or T-cells have been associated with atherosclerosis and impaired CD4 + T-cell reconstitution and progression in HIV-infected individuals on treatment 23 – 27 . However, CMV-specific T-cell responses in individuals with poor CD4 + T-cell recovery have not been completely characterized.…”

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…The precise mechanism by which HBV, HCV, and CMV coinfections may have deleterious effects on CD4 + T-cell count recovery is unclear. The impaired immunological recovery in HBV-, HCV-, or CMV-coinfected patients could be due to the destruction of CD4 + T cells by coinfection-mediated CD4 + T-cell activation, apoptosis, or exhaustion [145][146][147][148][149]. Others studies did not show an association between HBV,142,150,151 HCV,152,153 or CMV 154 coinfection and immunological recovery.…”

Potential contribution of gut microbiota and systemic inflammation on HIV vaccine effectiveness and vaccine design

“…CMV infection is prevalent in Africa and may contribute to a lower vaccine response observed in this population. Furthermore, CMV co-infection has been associated with faster disease progression and elevated CMV-specific IgG antibody levels in untreated HIV-infected individuals, further contributing to disease progression and immune activation [ 42 ]. For patients receiving long-term antiretroviral therapy (ART), CMV-co-infection remains an independent contributor to persistent CD8 T-Cell expansion and inflammation [ 43 ].…”