Disease Progression in HIV-1–Infected Viremic Controllers

Groves, Katherine; Bibby, David F.; Clark, Duncan A.; Isaksen, A; Deayton, Jane R; Anderson, Jane; Orkin, Chloe; Stagg, Andrew J.; McKnight, Áine

doi:10.1097/qai.0b013e318269c414

Cited by 27 publications

(31 citation statements)

References 46 publications

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“…These results are consistent with previous studies, which reported that the majority of circulating CD8 + T cells in individuals with chronic HIV-1 infection were mature effector and effector memory CD8 + T cells (23,24). However, in a cross sectional study by Groves et al (19), discord controllers and typical controllers had higher numbers of naive CD8 + T cells and reduced CD8 + T cell activation, compared with the patients with rapidly progressing disease. Notably, Groves et al defined discord controllers as patients with a viral RNA load <2,000 copies/ml and <450 CD4 + T cells/mm 3 , with the viral load of discord controllers ranging between 100.3 and 1,043.0 copies/ml.…”

Section: Discussionsupporting

confidence: 92%

“…HIV-1. Based on the expression of CD45RA and CD62L, human CD8 + T cells can be divided into four subsets with distinct homing and functional properties: Naïve (CD45RA + CD62L + ), central memory (CD45RA -CD62L + ), effector memory (CD45RA -CD62L -) and effector (CD45RA + CD62L -) cells (18,19). In the present study, the CD8 + T cell subsets were determined in patients with HIV-1.…”

Section: Subsets Of Circulating Cd8 + T Cells Are Altered In Patientsmentioning

confidence: 93%

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Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Jin

Cheng

et al. 2017

Molecular Medicine Reports

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The differentiation and response ofCD8+ T cells is vital in host defense against human immunodeficiency virus type 1 (HIV-1). MicroRNA (miR)‑155 is an important regulator of T cell differentiation. However, the profile of miR-155 in HIV‑1 infected individuals and its association with CD8+ T cell differentiation remain to be fully elucidated. The present cross‑sectional study was performed involving 63 HIV‑1‑infected patients undergoing highly active antiretroviral therapy (HAART), 31 HAART‑naïve patients and 35 healthy controls. The levels of miR‑155 in CD8+ T cells were detected using reverse transcription‑quantitative polymerase chain reaction analysis. Subsets of CD8+ T cell differentiation were detected using flow cytometry. The results revealed that the discord controllers and HAART‑naïve patients showed higher percentages of effector and effector memory cells, and lower percentages of naïve cells (P<0.05). The levels of miR‑155 in CD8+ T cells from the HIV‑1‑infected patients were higher, particularly in the discord controllers and HAART naïve patients (P<0.01). The expression levels of miR‑155 were positively correlated with the percentages of effector and effector memory CD8+ T cells, and negatively correlated with the percentages of naïve and central memory CD8+ T cells (P<0.01). Taken together, these findings suggested that the levels of miR‑155 in CD8+ T cells of patients with HIV-1 were increased and asso-ciated with CD8+ T cell differentiation.

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Section: Discussionsupporting

confidence: 92%

Section: Subsets Of Circulating Cd8 + T Cells Are Altered In Patientsmentioning

confidence: 93%

Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Jin

Cheng

et al. 2017

Molecular Medicine Reports

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“…Terminology then changed to refer to such atypical HIV-1 + individuals as “Elite controllers,” “Elite suppressors,” and “HIV controllers” (Deeks and Walker, 2007; Blankson, 2010; Migueles and Connors, 2010). More recently, an additional group of individuals exhibiting a disparate course of clinical disease have been described and termed “Discord controllers” (Groves et al, 2012). These individuals control viral replication to BLD of the routinely available viral load assay, but demonstrate peripheral blood CD4 T-cell counts lower than the normal range, therefore failing to meet the inclusion criteria for LTNP status.…”

Section: The Long-term Non-progressor: Criteria Of Definition and Emumentioning

confidence: 99%

Long-Term Non-Progression and Broad HIV-1-Specific Proliferative T-Cell Responses

Imami¹,

Westrop²,

Grageda³

et al. 2013

Front. Immunol.

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Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term non-progressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilizing cure, involving clearance of virus from the host, remains a primary aim, a “functional cure” may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilized in future strategies designed to improve upon existing therapy. The aim will be to induce long-term non-progressor or elite controller status in every infected host, through immune-mediated control of viremia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

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“…More recently, Groves et al [ 16 ▪▪ ] identified ART-naive patients who had maintained a viral load less than 2000 copies/ml for more than 12 months. Typical controllers had an average recent CD4 cell count more than 450 cells/μl (2.1% of population), whereas discord controllers had an average recent CD4 cell count less than 450 cells/μl (0.6%).…”

Section: Long-term Nonprogressors and Elite Controllersmentioning

confidence: 99%

“…As the two groups of individuals appear to be clinically distinct, suggesting differences in the processes that lead to long-term nonprogression and elite control, several research groups have attempted to investigate whether there are any demographic or biological differences between these two patient groups [ 4 ]. Groves et al [ 16 ▪▪ ] reported a more marked depletion of the naive T-cell subset in discord controllers than in typical controllers but a trend towards increased activated effector memory CD4 cells in typical controllers. CD8 T-cell activation was increased to a similar level (compared with noncontrollers) in both controller groups.…”

Section: Long-term Nonprogressors and Elite Controllersmentioning

confidence: 99%

The natural history of HIV infection

Sabin¹,

Lundgren²

2013

Current Opinion in HIV and AIDS

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Purpose of reviewTo review recent published literature around three areas: long-term nonprogression/viral control; predictors of viral load set point/disease progression; and the potential impact of antiretroviral therapy (ART) in early HIV infection.Recent findingsThe natural course of untreated HIV infection varies widely with some HIV-positive individuals able to maintain high CD4 cell counts and/or suppressed viral load in the absence of ART. Although similar, the underlying mechanistic processes leading to long-term nonprogression and viral control are likely to differ. Concerted ongoing research efforts will hopefully identify host factors that are causally related to these phenotypes, thus providing opportunities for the development of novel treatment or preventive strategies. Although there is increasing evidence that initiation of ART during primary infection may prevent the immunological deterioration which would otherwise be seen in untreated HIV infection, recent studies do not address the longer term clinical benefits of ART at this very early stage.SummaryA better understanding of the relative influences of viral, host, and environmental factors on the natural course of HIV infection has the potential to identify novel targets for intervention to prevent and treat HIV-infected persons.

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Disease Progression in HIV-1–Infected Viremic Controllers

Cited by 27 publications

References 46 publications

Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Elevated expression of miR-155 is associated with the differentiation of CD8+ T cells in patients with HIV-1

Long-Term Non-Progression and Broad HIV-1-Specific Proliferative T-Cell Responses

The natural history of HIV infection

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