Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART.
Ontology highlight
ABSTRACT:
SUBMITTER: Dan JM
PROVIDER: S-EPMC4868660 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThe association between subclinical cytomegalovirus (CMV) replication and HIV persistence has not been investigated in cis-gender women with HIV.MethodsFifty virologically suppressed female participants with HIV were prospectively enrolled and provided oral, vaginal, and urine samples and peripheral blood mononuclear cells at 1 cross-sectional time point. CMV DNA was quantified in each specimen by real-time polymerase chain reaction (PCR). Cellular HIV DNA and HIV RNA transcripts (unspliced and multiply spliced [ms] encoding tat-rev) were quantified by droplet digital (dd) PCR in peripheral blood cells. Forty-nine male individuals with HIV and CMV (historical data) were used as controls.ResultsLevels of cellular HIV DNA and unspliced HIV RNA were not different between sexes, but female participants had less detectable msHIV RNA and CMV DNA compared with males (both P < .01). Unlike previously described for males, the presence of CMV DNA was not associated with increased HIV DNA in females. Among female participants, premenopausal status was independently associated with lower HIV DNA compared with postmenopause, after adjusting for nadir CD4 count (P < .01).ConclusionsFemale participants with HIV had reduced cellular HIV RNA and less subclinical CMV DNA compared with males but overall similar HIV DNA levels in our study. Postmenopausal status was independently associated with higher HIV DNA levels among female participants.
| S-EPMC7415302 | biostudies-literature
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.
| S-EPMC3937334 | biostudies-literature
Project description:Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22-40 years) and 26 older (50-71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels. Among older participants, higher HIV DNA levels were significantly associated with more severe neurocognitive impairment (p = 0.005), particularly in the Executive Functions domain (p = 0.004). No association was observed between HIV DNA and neurocognition among younger individuals. Despite significantly increased inflammation observed in the older group, none of the inflammatory markers were associated with neurocognitive impairment among older HIV+ individuals (p > 0.05). Our study supports the involvement of peripheral HIV DNA reservoir in the pathogenesis of neurocognitive disorder during suppressive ART. Correlates of neurocognitive impairment might differ between younger and older adults, suggesting that future treatment and prevention strategies for HIV-associated neurocognitive disorders likely need to be tailored based on age.
| S-EPMC4658529 | biostudies-literature
Project description:INTRODUCTION:People living with HIV (PLWH) need to adhere to antiretroviral therapy (ART) to achieve optimal health. One reason for ART nonadherence is HIV-related stigma. OBJECTIVES:We aimed to examine whether HIV treatment self-efficacy (an intrapersonal mechanism) mediates the stigma-adherence association. We also examined whether self-efficacy and the concern about being seen while taking HIV medication (an interpersonal mechanism) are parallel mediators independent of each other. METHODS:A total of 180 people living with HIV self-reported internalized HIV stigma, ART adherence, HIV treatment self-efficacy, and concerns about being seen while taking HIV medication. We calculated bias-corrected 95% confidence intervals for indirect effects using bootstrapping to conduct mediation analyses. RESULTS:Adherence self-efficacy mediated the relationship between internalized stigma and ART adherence. Additionally, self-efficacy and concern about being seen while taking HIV medication uniquely mediated and explained almost all the stigma-adherence association in independent paths (parallel mediation). CONCLUSION:These results can inform intervention strategies to promote ART adherence.
| S-EPMC5147512 | biostudies-literature
Project description:The HIV-1 reservoir is the major hurdle to a cure. We here evaluate viral and host characteristics associated with reservoir size and long-term dynamics in 1,057 individuals on suppressive antiretroviral therapy for a median of 5.4 years. At the population level, the reservoir decreases with diminishing differences over time, but increases in 26.6% of individuals. Viral blips and low-level viremia are significantly associated with slower reservoir decay. Initiation of ART within the first year of infection, pretreatment viral load, and ethnicity affect reservoir size, but less so long-term dynamics. Viral blips and low-level viremia are thus relevant for reservoir and cure studies.
| S-EPMC6642170 | biostudies-literature
Project description:The comprehensive characterization and quantification of the HIV tissue reservoirs is required to design appropriate therapeutic intervention(s) to achieve a cure. While pioneering studies demonstrated that HIV replication and spreading mainly occur in lymphoid tissues, the identification of specific cell subsets harboring replication competent virus in lymphoid tissues has long been neglected. In this context, we and others have recently shown that gut memory CD4 T cells, lymph node T follicular helper (Tfh) cells and tissue macrophages represent major HIV/SIV tissue reservoirs. Notably, Tfh cell differentiation is a multi-stage process that requires long-lasting interactions with lymph node (LN) dendritic cells (DCs) and pre-germinal center B cells in a specific cytokine/chemokine microenvironment. Lymph node DCs are endowed with an exceptional T-cell stimulatory potential and can either migrate from the periphery to the draining lymph node (migratory DCs) or locate in the LN for their entire life span (resident DCs). On the basis of these unique properties, long-term persistence of LN DCs infected with replication competent virus may represent the initial trigger of viral rebound post ART interruption and may therefore represent a major obstacle to HIV cure. We demonstrate that LN migratory DCs are infected with replication competent virus and persist despite suppressive ART. In addition, we identified the mechanisms associated with i) LN DC susceptibility to HIV infection and ii) long term persistence of HIV-infected LN DCs i.e. proliferation of infected cells in tissue sanctuaries.
2023-09-13 | GSE196066 | GEO
Project description:Blockade of the programmed cell death protein/ligand 1 (PD-1/PD-L1) pathway with monoclonal antibodies (mAb) is now commonly used for cancer immunotherapy and has therapeutic potential in chronic viral infections including HIV-1. PD-1/PD-L1 blockade could augment HIV-1-specific immune responses and reverse HIV-1 latency, but the latter effect has not been clearly shown. We tested the ability of the human anti-PD-L1 mAb BMS-936559 and the human anti-PD-1 mAb nivolumab to increase HIV-1 virion production ex vivo from different peripheral blood mononuclear cell populations obtained from donors on suppressive antiretroviral therapy (ART). Fresh peripheral blood mononuclear cells (PBMC), CD8-depleted PBMC, total CD4+ T cells, and resting CD4+ T cells were purified from whole blood of HIV-1-infected donors and cultured in varying concentrations of BMS-936559 (20, 5, or 1.25?g/mL) or nivolumab (5 or 1.25?g/mL), with or without anti-CD3/CD28 stimulatory antibodies. Culture supernatants were assayed for virion HIV-1 RNA by qRT-PCR. Ex vivo exposure to BMS-936559 or nivolumab, with or without anti-CD3/CD28 stimulation, did not consistently increase HIV-1 virion production from blood mononuclear cell populations. Modest (2-fold) increases in virus production were observed in a subset of donors and in some cell types but were not reproducible in longitudinal samples. Cell surface expression of PD-1 and PD-L1 were not associated with changes in virus production. Ex vivo blockade of the PD-1 axis alone has limited effects on HIV-1 latency.
| S-EPMC6347234 | biostudies-literature
Project description:The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients' hurdle towards a cure.
| S-EPMC7608612 | biostudies-literature
Project description:Facility-based antiretroviral therapy (ART) provision for stable patients with HIV congests health services in resource-limited countries. We assessed outcomes and risk factors for attrition after decentralization to community-based ART refill centers among 2603 patients with HIV in Kinshasa, Democratic Republic of Congo, using a multilevel Poisson regression model. Death, loss to follow-up, and transfer out were 0.3%, 9.0%, and 0.7%, respectively, at 24 months. Overall attrition was 5.66/100 person-years. Patients with >3 years on ART, >500 cluster of differentiation type-4 count, body mass index >18.5, and receiving nevirapine but not stavudine showed reduced attrition. ART refill centers are a promising task-shifting model in low-prevalence urban settings with high levels of stigma and poor ART coverage.
| S-EPMC5305289 | biostudies-literature
Project description:Lifelong treatment is required for people living with HIV as current antiretroviral therapy (ART) does not eradicate HIV infection. Latently infected cells are essentially indistinguishable from uninfected cells and cannot be depleted by currently available approaches. This study evaluated antibody mediated transient CD4+ T cell depletion as a strategy to reduce the latent HIV reservoir. Anti-CD4 antibodies effectively depleted CD4+ T cells in the peripheral blood and tissues of humanized mice. We then demonstrate that antibody-mediated CD4+ T cell depletion of HIV infected ART-suppressed animals results in substantial reductions in cell-associated viral RNA and DNA levels in peripheral blood cells over the course of anti-CD4 antibody treatment. Recovery of CD4+ T cells was observed in all tissues analyzed except for the lung 26 days after cessation of antibody treatment. After CD4+ T cell recovery, significantly lower levels of cell-associated viral RNA and DNA were detected in the tissues of anti-CD4 antibody-treated animals. Further, an 8.5-fold reduction in the levels of intact HIV proviral DNA and a 3.1-fold reduction in the number of latently infected cells were observed in anti-CD4-antibody-treated animals compared with controls. However, there was no delay in viral rebound when ART was discontinued in anti-CD4 antibody-treated animals following CD4+ T cell recovery compared with controls. Our results suggest that transient CD4+ T cell depletion, a long-standing clinical intervention that might have an acceptable safety profile, during suppressive ART can reduce the size of the HIV reservoir in humanized mice.
| S-EPMC10699604 | biostudies-literature