Dataset Information

Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART.

ABSTRACT: HIV-infected men who have sex with men are nearly universally coinfected with cytomegalovirus (CMV). In this study of 45 HIV-infected men who have sex with men virologically suppressed on ART, we found that presence of seminal CMV DNA shedding and higher levels of systemic cellular HIV RNA transcription were both independently associated with increased PD-1 expression on circulating CD4 T cells, but not with higher levels of senescent (CD57) T cells. In addition, greater HIV RNA transcription was associated with lower CD57 expression on CD8 T cells. Although causality cannot be inferred from this retrospective study, these results suggest that asymptomatic CMV replication and residual cellular HIV transcription may contribute to persistent immune dysregulation during suppressive ART.

SUBMITTER: Dan JM

PROVIDER: S-EPMC4868660 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART.

Dan Jennifer M JM Massanella Marta M Smith Davey M DM Spina Celsa A CA Schrier Rachel R Daar Eric S ES Dube Michael P MP Morris Sheldon R SR Gianella Sara S

Journal of acquired immune deficiency syndromes (1999) 20160601 2

HIV-infected men who have sex with men are nearly universally coinfected with cytomegalovirus (CMV). In this study of 45 HIV-infected men who have sex with men virologically suppressed on ART, we found that presence of seminal CMV DNA shedding and higher levels of systemic cellular HIV RNA transcription were both independently associated with increased PD-1 expression on circulating CD4 T cells, but not with higher levels of senescent (CD57) T cells. In addition, greater HIV RNA transcription wa ...[more]

PMID: 26818740

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Project description:ObjectivesEvaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.MethodsBetween 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time.ResultsMean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens.ConclusionsThere is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Project description:BackgroundChronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase "immunosenesence" of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear.MethodsWe compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection.ResultsCompared to HIV-uninfected adults without CMV (n=12), those with asymptomatic CMV infection (n=31) had a higher proportion of CD28-CD8+ T cells expressing CD57 (P=0.005). Older age was also associated with greater proportions of CD28-CD8+ T cells expressing CD57 (rho: 0.47, P=0.007). In contrast, untreated HIV-infected CMV+ participants (n=55) had much lower proportions of CD28- CD8+ cells expressing CD57 than HIV-uninfected CMV+ participants (P<0.0001) and were enriched for less well-differentiated CD28- transitional memory (TTR) CD8+ T cells (P<0.0001). Chronically HIV-infected adults maintaining ART-mediated viral suppression (n=96) had higher proportions of CD28-CD8+ T cells expressing CD57 than untreated patients (P<0.0001), but continued to have significantly lower levels than HIV-uninfected controls (P=0.001). Among 45 HIV-infected individuals initiating their first ART regimen, the proportion of CD28-CD8+ T cells expressing CD57 declined (P<0.0001), which correlated with a decline in percent of transitional memory CD8+ T cells, and appeared to be largely explained by a decline in CD28-CD57- CD8+ T cell counts rather than an expansion of CD28-CD57+ CD8+ T cell counts.ConclusionsUnlike CMV and aging, which are associated with terminal differentiation and proliferation of effector memory CD8+ T cells, HIV inhibits this process, expanding less well-differentiated CD28- CD8+ T cells and decreasing the proportion of CD28- CD8+ T cells that express CD57.

Dataset Information

Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART.

Publications

Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART.

Similar Datasets

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