Biphasic decay kinetics suggest progressive slowing in turnover of latently HIV-1 infected cells during antiretroviral therapy

Fischer, Marek; Joos, Béda; Niederöst, Barbara; Kaiser, Philipp; Hafner, Roland; Wyl, Viktor von; Ackermann, Martina; Weber, Rainer; Günthard, Huldrych F.

doi:10.1186/1742-4690-5-107

Cited by 45 publications

(86 citation statements)

References 51 publications

(95 reference statements)

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“…The model assumes a heterogeneous population of latently and persistently infected cells having occasional transcriptional bursts to increase their level of RNA transcription which is consistent with experimental data from Fischer et al [12].…”

Section: Discussionsupporting

confidence: 75%

“…It is important to note, however, that the characteristic decay profile in the study by Fischer et al [12] could also be a result of differential trafficking of virus particles and HIV-1-infected subpopulations of cells between the blood and lymphoid tissue. Furthermore, it has also been suggested that the virion clearance rate from the blood corresponds to a virion efflux to other organs where the virus is ultimately However, we have excluded this effect for simplicity.…”

Section: Cc-by-nc-nd 40 International License Peer-reviewed) Is the mentioning

confidence: 94%

“…We first devised a detailed model of the within-host dynamics of HIV-1 that is based on the observations of different subclasses of HIV-1-infected cells in the study by Fischer et al [12]. The five subclasses are HIV-1 DNA + , low, medium and high HIV-1 RNA expressing and cells that have virion-enclosed HIV-1 RNA associated with them (also see Methods).…”

Section: Resultsmentioning

confidence: 99%

“…Latently infected cells (L 1 and L 2 ) were assumed to transcribe HIV-1 RNA at low or intermediate levels [12,13]. Infected cells that are HIV-1 DNA positive, but HIV-1 RNA negative, were assumed to remain transcriptionally silent during the observation period and considered as defectively infected cells…”

Section: Resultsmentioning

confidence: 99%

“…The study identified four distinct viral transcriptional classes: two overlapping cell classes of high viral transcriptional activity, representative of a virus producing phenotype; and two cell classes that express HIV-1 RNA at low and intermediate levels that match definitions of viral latency [12,13].…”

mentioning

confidence: 99%

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Quantifying the turnover of transcriptional subclasses of HIV-1-infected cells

Althaus

Joos

Perelson

et al. 2013

Preprint

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HIV-1-infected cells in peripheral blood can be grouped into different transcriptional subclasses. Quantifying the turnover of these cellular subclasses can provide important insights into the viral life cycle and the generation and maintenance of latently infected cells. We used previously published data from five patients chronically infected with HIV-1 that initiated combination antiretroviral therapy (cART).Patient-matched PCR for unspliced and multiply spliced viral RNAs combined with limiting dilution analysis provided measurements of transcriptional profiles at the single cell level. Furthermore, measurement of intracellular transcripts and extracellular virion-enclosed HIV-1 RNA allowed us to distinguish productive from non-productive cells. We developed a mathematical model describing the dynamics of plasma virus and the transcriptional subclasses of HIV-1-infected cells. Fitting the model to the data allowed us to better understand the phenotype of different transcriptional subclasses and their contribution to the overall turnover of HIV-1 before and during cART. The average number of virus-producing cells in peripheral blood is small during chronic infection (25.7 cells ml −1 ). We find that 14.0%, 0.3% and 21.2% of infected cells become defectively, latently and persistently infected cells, respectively. Assuming that the infection is homogenous throughout the body, we estimate an average in vivo viral burst size of 2.1 × 10 4 virions per cell. Our study provides novel quantitative insights into the turnover and develop-

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Section: Discussionsupporting

confidence: 75%

Section: Cc-by-nc-nd 40 International License Peer-reviewed) Is the mentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Quantifying the turnover of transcriptional subclasses of HIV-1-infected cells

Althaus

Joos

Perelson

et al. 2013

Preprint

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Time course of cellular HIV-DNA and low-level HIV viremia in HIV–HCV co-infected patients whose HCV infection had been successfully treated with directly acting antivirals

Parisi

Andreis

Basso

et al. 2017

Med Microbiol Immunol

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This longitudinal study described cellular HIV-DNA changes and their correlation with HIV low-level plasma viremia (LLV) in HIV-HCV co-infected patients on successful antiretroviral and anti-HCV therapy by treatment with direct-acting antivirals (DAA). Thirty-nine patients were examined prior to the start of DAA (T0), after week 12 (T1) and 24 weeks (T2) of anti-HCV therapy. Cellular PBMC HIV-DNA was analysed as an absolute value and as the percentage of increase or decrease from T0 to T2. Patients were classified as having undetectable plasma HIV viraemia (UV) or LLV in the year before the start of anti-HCV treatment and within the T0-T2 study period. Thirty-five patients (89.7%) of the 39 subjects enrolled had the same plasma HIV viraemia control in the year before HCV treatment and in the T0-T2 interval. The HIV-DNA value at T0 and at T2 was higher in patients with LLV than in subjects with UV (p = 0.015 and p = 0.014, respectively). A similar proportion of patients with LLV and UV experienced an increase or decrease of HIV-DNA from T0 to T2. The percentage increase in HIV-DNA value (262.8%) from T0 to T2 was higher compared to the decrease (43.5%) in patients with UV (p = 0.012), and it was higher compared to the percentage increase in HIV-DNA value reported in subjects with LLV (262.8 versus 49%, p = 0.026). HIV-HCV co-infected patients experienced a multifaceted perturbation of cellular HIV-DNA levels within a 24-week period during anti-HCV treatment; the extent of the phenomenon was greater in subjects with UV. Fast HCV-RNA clearance seemed to have a greater influence on the cellular reservoir than on plasma HIV-RNA.

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Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat

Wang¹,

Yi²,

Green³

et al. 2015

Cardiovascular Pathology

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With effective antiretroviral therapy (ART), many HIV-infected people die of diseases other than acquired immune deficiency syndrome (AIDS). In particular, coronary artery disease has emerged as one of most critical complications of HIV infection and a major cause of morbidity and mortality. Although reportedly antiretroviral combination therapy itself may accelerate atherosclerosis by enhancing dyslipidemia, most recent epidemiological studies support the notion that HIV infection itself contributes to cardiovascular disease. However, it is still a mystery how the virus can contribute to cardiovascular disease development even while suppressed by ARTs. This review discusses the current understanding of interactions between HIV infection and cardiovascular diseases in both clinical and experimental studies with special focus on those viral proteins which are still produced by HIV. This will help infectious disease/vascular biology experts to gain insights into the pathophysiological mechanisms of HIV associated cardiovascular disease and new trends to treat and prevent cardiovascular disease in the HIV infected population.

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Biphasic decay kinetics suggest progressive slowing in turnover of latently HIV-1 infected cells during antiretroviral therapy

Cited by 45 publications

References 51 publications

Quantifying the turnover of transcriptional subclasses of HIV-1-infected cells

Quantifying the turnover of transcriptional subclasses of HIV-1-infected cells

Time course of cellular HIV-DNA and low-level HIV viremia in HIV–HCV co-infected patients whose HCV infection had been successfully treated with directly acting antivirals

Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat

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