| Publication Abstract Display | | Type: Published Abstract | | Title: Effects of subclinical CMV replication on T-cell activation during early ART. | | Authors: Christensen-Quick A, Massanella M, Frick A, Spina C, Vargas M, Nakazawa M, Anderson C, Gianella S | | Year: | | Publication: CROI 2018 | | Volume: Issue: Pages: | | Abstract:We previously showed that subclinical Cytomegalovirus (CMV) replication was associated with increased activation of CD4+ T cells during chronic HIV-infection and with a slower decay of HIV DNA in people starting antiretroviral therapy (ART) during early HIV infection. Here, we investigate changes in T cell activation that associate with CMV replication in the setting of early ART.
We investigated 246 peripheral blood mononuclear cell (PBMC) samples from 64 individuals starting ART during early HIV infection with subsequent virologic suppression up to 90 months (<50cp/ml, no viral blips, median 4 time-points/participant). In each PBMC sample, levels of CMV DNA were measured by ddPCR. Expression of immunological markers of activation (HLA-DR+CD38+) on five T-cell memory subsets [Naïve (TN, CD27+CD45RA+), Stem Cell Memory (TSCM, CD27+CD45RA+CD95+), Central Memory (TCM, CD27+CD45RA-), Effector Memory (TEM, CD27-, CD45RA-), and Terminally Differentiated (TTD, CD27-, CD45RA+)] were measured in CD4+ and CD8+ T cells by flow cytometry. Significant differences in % of activated lymphocyte markers by CMV shedding status were identified using Generalized Linear Mixed Effects models. Models were checked for the effects of relevant covariates (Nadir CD4+, Time to ART, Race, Age, and Peak HIV RNA).
Participants started ART within a median of 3 months of estimated date of HIV infection (IQR: 1.5-8.5), and were followed for a median of 33 months (IQR: 19-50) while on suppressive ART. During follow-up, CMV was detected in 60/246 time points. Individuals with detectable CMV had significantly higher % of activated CD8+ TEM and TTD subsets at the time of ART initiation, but no differences in CD8+ TN or TCM (Table 1). We did not detect differences in CD4+ T cell activation at ART start. Over time, detectable CMV was associated with faster decay of activated CD8+ T cells (TEM and TTD). Interestingly, during CMV replication, activated CD4+ TSCM presented a significantly slower decay rate, compared with samples with no detectable CMV. These results persisted when relevant covariates were included in the models.
Unlike chronic ART, no effect of subclinical CMV replication was observed on CD4+ T cell activation in the setting of early ART start. While CD8+ T cell activation was initially elevated in the setting of CMV replication, it normalized rapidly during early ART. The effect of CMV on TSCM activation merits further evaluation for its relevancy to HIV persistence. |
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