The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Daniel R Kuritzkes - One of the best experts on this subject based on the ideXlab platform.
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Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral Treatment Interruption.
Pathogens & immunity, 2017Co-Authors: You Jeong Park, Ronald J Bosch, Daniel R Kuritzkes, John W. Mellors, Behzad Etemad, Hayat Ahmed, Vivek Naranbhai, Evgenia Aga, Michael F. Para, Rajesh T. GandhiAbstract:Identifying host determinants associated with HIV Reservoir Size and viral rebound timing after an analytic treatment interruption (ATI) is an important step in the search for an HIV functional cure. A pooled analysis of 103 participants from four AIDS Clinical Trials Group ATI studies to identify the association between HLA class I alleles with HIV Reservoir Size and viral rebound timing. Total HIV DNA and cell-associated HIV RNA (CA-RNA) were quantified in pre-ATI peripheral blood mononuclear cell samples, and residual plasma viremia was measured using the single-copy assay. HLA class I typing was performed and we generated an odds ratio (OR) of predicted HLA effect on HIV viremia control for each individual and compared this with time to viral rebound, and levels of HIV DNA and CA-RNA. There was no significant association between the HLA ORs and levels of HIV DNA or CA-RNA, but carriage of protective HLA-B alleles (lower OR scores) was associated with delayed viral rebound ( P= 0.02). Higher OR scores at the HLA-C locus were associated with longer duration of ART treatment ( P= 0.01) and this trend was also seen with the combined OR score ( P= 0.007). Individuals with protective HLA-B alleles had delayed viral rebound after treatment interruption that was not explained by differences in baseline Reservoir Size. The results indicate the vital role of cellular host immunity in preventing HIV rebound and the importance of taking into account the HLA status of study participants being evaluated in HIV cure trials.
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Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV.
PLoS pathogens, 2016Co-Authors: Alison L. Hill, Emily Hanhauser, Daniel R Kuritzkes, Daniel I. S. Rosenbloom, Robert F. Siliciano, Edward Goldstein, Timothy J HenrichAbstract:Monitoring the efficacy of novel Reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely Size of the remaining Reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of Reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the Reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial Size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect Reservoir assays. Our findings suggest that large numbers of patients-between 40 and 150-will be necessary to reliably estimate the Reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two "Boston patients", recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual Reservoir that eventually caused rebound. Together, these tools will aid HIV researchers in the evaluating new potentially-curative strategies that target the latent Reservoir.
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ccr5 δ32 heterozygosity hiv 1 Reservoir Size and lymphocyte activation in individuals receiving long term suppressive antiretroviral therapy
The Journal of Infectious Diseases, 2016Co-Authors: Timothy J Henrich, Emily Hanhauser, Linda Harrison, Christine D Palmer, Marisol Romerotejeda, Stephanie Jost, Ronald J Bosch, Daniel R KuritzkesAbstract:We conducted a case-controlled study of the associations of CCR5-Δ32 heterozygosity with human immunodeficiency virus type 1 (HIV-1) Reservoir Size, lymphocyte activation, and CCR5 expression in 114 CCR5(Δ32/WT) and 177 wild-type CCR5 AIDS Clinical Trials Group participants receiving suppressive antiretroviral therapy. Overall, no significant differences were found between groups for any of these parameters. However, higher levels of CCR5 expression correlated with lower amounts of cell-associated HIV-1 RNA. The relationship between CCR5-Δ32 heterozygosity, CCR5 expression, and markers of HIV-1 persistence is likely to be complex and may be influenced by factors such as the duration of ART.
Jacques Fellay - One of the best experts on this subject based on the ideXlab platform.
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heritability of the hiv 1 Reservoir Size and decay under long term suppressive art
Nature Communications, 2020Co-Authors: Chenjie Wan, Nadine Bachmann, Venelin Mitov, Francois Blanquart, Susana Posada Cespedes, Teja Turk, Kathrin Neumann, Niko Beerenwinkel, Jasmina Bogojeska, Jacques FellayAbstract: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.
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determinants of hiv 1 Reservoir Size and long term dynamics during suppressive art
Nature Communications, 2019Co-Authors: Nadine Bachmann, Teja Turk, Kathrin Neumann, Niko Beerenwinkel, Jasmina Bogojeska, Jacques Fellay, Chantal Von Siebenthal, Valentina VongradAbstract: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.
Mark J Embrechts - One of the best experts on this subject based on the ideXlab platform.
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Reservoir Size spectral radius and connectivity in static classification problems
International Conference on Artificial Neural Networks, 2009Co-Authors: Luis A Alexandre, Mark J EmbrechtsAbstract:Reservoir computing is a recent paradigm that has proved to be quite effective given the classical difficulty in training recurrent neural networks. An approach to using Reservoir recurrent neural networks has been recently proposed for static problems and in this paper we look at the influence of the Reservoir Size, spectral radius and connectivity on the classification error in these problems. The main conclusion derived from the performed experiments is that only the Size of the Reservoir is relevant with the spectral radius and the connectivity of the Reservoir not affecting the classification performance.
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ICANN (1) - Reservoir Size, Spectral Radius and Connectivity in Static Classification Problems
Artificial Neural Networks – ICANN 2009, 2009Co-Authors: Luis A Alexandre, Mark J EmbrechtsAbstract:Reservoir computing is a recent paradigm that has proved to be quite effective given the classical difficulty in training recurrent neural networks. An approach to using Reservoir recurrent neural networks has been recently proposed for static problems and in this paper we look at the influence of the Reservoir Size, spectral radius and connectivity on the classification error in these problems. The main conclusion derived from the performed experiments is that only the Size of the Reservoir is relevant with the spectral radius and the connectivity of the Reservoir not affecting the classification performance.
Niko Beerenwinkel - One of the best experts on this subject based on the ideXlab platform.
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heritability of the hiv 1 Reservoir Size and decay under long term suppressive art
Nature Communications, 2020Co-Authors: Chenjie Wan, Nadine Bachmann, Venelin Mitov, Francois Blanquart, Susana Posada Cespedes, Teja Turk, Kathrin Neumann, Niko Beerenwinkel, Jasmina Bogojeska, Jacques FellayAbstract: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.
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host genomics of the hiv 1 Reservoir Size and its decay rate during suppressive antiretroviral treatment
medRxiv, 2019Co-Authors: Christian W Thorball, Nadine Bachmann, Teja Turk, Kathrin Neumann, Niko Beerenwinkel, Jasmina Bogojeska, Chantal Von Siebenthal, Valentina Vongrad, Alessandro Borghesi, Volker RothAbstract:Introduction A major hurdle to HIV-1 eradication is the establishment of a latent viral Reservoir early after primary infection. Several factors are known to influence the HIV-1 Reservoir Size and decay rate on suppressive antiretroviral treatment (ART), but little is known about the role of human genetic variation. Methods We measured the Reservoir Size at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readouts: the Reservoir Size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants. Results Genome- and exome-wide analyses did not reveal any significant association with the Size of the HIV-1 Reservoir or its decay rate on suppressive ART. Conclusions Our results point to a limited influence of human genetics on the Size of the HIV-1 Reservoir and its long-term dynamics in successfully treated individuals.
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determinants of hiv 1 Reservoir Size and long term dynamics during suppressive art
Nature Communications, 2019Co-Authors: Nadine Bachmann, Teja Turk, Kathrin Neumann, Niko Beerenwinkel, Jasmina Bogojeska, Jacques Fellay, Chantal Von Siebenthal, Valentina VongradAbstract: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.
Timothy J Henrich - One of the best experts on this subject based on the ideXlab platform.
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Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV.
PLoS pathogens, 2016Co-Authors: Alison L. Hill, Emily Hanhauser, Daniel R Kuritzkes, Daniel I. S. Rosenbloom, Robert F. Siliciano, Edward Goldstein, Timothy J HenrichAbstract:Monitoring the efficacy of novel Reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set of mathematical and statistical modeling tools to aid in the design and interpretation of ART-interruption trials. We show how the likely Size of the remaining Reservoir can be updated in real-time as patients continue off treatment, by combining the output of laboratory assays with insights from models of Reservoir dynamics and rebound. We design an optimal schedule for viral load sampling during interruption, whereby the frequency of follow-up can be decreased as patients continue off ART without rebound. While this scheme can minimize costs when the chance of rebound between visits is low, we find that the Reservoir will be almost completely reseeded before rebound is detected unless sampling occurs at least every two weeks and the most sensitive viral load assays are used. We use simulated data to predict the clinical trial Size needed to estimate treatment effects in the face of highly variable patient outcomes and imperfect Reservoir assays. Our findings suggest that large numbers of patients-between 40 and 150-will be necessary to reliably estimate the Reservoir-reducing potential of a new therapy and to compare this across interventions. As an example, we apply these methods to the two "Boston patients", recipients of allogeneic hematopoietic stem cell transplants who experienced large reductions in latent infection and underwent ART-interruption. We argue that the timing of viral rebound was not particularly surprising given the information available before treatment cessation. Additionally, we show how other clinical data can be used to estimate the relative contribution that remaining HIV+ cells in the recipient versus newly infected cells from the donor made to the residual Reservoir that eventually caused rebound. Together, these tools will aid HIV researchers in the evaluating new potentially-curative strategies that target the latent Reservoir.
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ccr5 δ32 heterozygosity hiv 1 Reservoir Size and lymphocyte activation in individuals receiving long term suppressive antiretroviral therapy
The Journal of Infectious Diseases, 2016Co-Authors: Timothy J Henrich, Emily Hanhauser, Linda Harrison, Christine D Palmer, Marisol Romerotejeda, Stephanie Jost, Ronald J Bosch, Daniel R KuritzkesAbstract:We conducted a case-controlled study of the associations of CCR5-Δ32 heterozygosity with human immunodeficiency virus type 1 (HIV-1) Reservoir Size, lymphocyte activation, and CCR5 expression in 114 CCR5(Δ32/WT) and 177 wild-type CCR5 AIDS Clinical Trials Group participants receiving suppressive antiretroviral therapy. Overall, no significant differences were found between groups for any of these parameters. However, higher levels of CCR5 expression correlated with lower amounts of cell-associated HIV-1 RNA. The relationship between CCR5-Δ32 heterozygosity, CCR5 expression, and markers of HIV-1 persistence is likely to be complex and may be influenced by factors such as the duration of ART.
