Active and Persistent Cytomegalovirus Infections Affect T Cells in Young Adult HIV Patients Commencing Antiretroviral Therapy

Abstract

Altered T cell profiles have been linked with metrics of persistent cytomegalovirus (CMV) infections in healthy aging and older HIV patients stable on antiretroviral therapy (ART). In this study, we use CMV DNA to identify active infections, and levels of CMV-reactive antibody to assess the persistent burden of CMV in a longitudinal study of 78 young adult patients beginning ART in Jakarta, Indonesia, with <200 CD4 T cells/μL. CMV antibodies, inflammatory markers (C-reactive protein [CRP], soluble interferon-α/β receptor) and T cell phenotypes were assessed before ART (V0) and after 1, 3, 6, and 12 months (V1-V12). CMV DNA was detected in 41 patients (52%) at V0, irrespective of CD4 T cell counts, gender, age, or plasma HIV RNA. CMV DNA+ patients had higher levels of antibody reactive with CMV Immediate Early 1 (IE-1) at V0 and V12 (p = 0.04), and with CMV lysate at V12 (p = 0.01). Detectable CMV DNA did not align with inflammatory markers, but associated with lower CD4/CD8 ratios until V3. CMV antibody levels correlated inversely with proportions of naive CD4 and CD8 T cells, and directly with proportions of CD57⁺ and activated memory T cells (CD3⁺ CD45RA^-) after 3-12 months on ART. Overall, active CMV replication is common in HIV patients beginning ART in Indonesia and associates with low CD4/CD8 ratios. Elevated levels of CMV-reactive antibody measured on ART also mark a depletion of naive T cells, accumulation of memory T cells, and may be a stable metric of the burden of CMV.

Keywords: CMV; HIV; Indonesia; T cells; antiretroviral therapy.