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Jatin Arora, Paul J McLaren, Nimisha Chaturvedi, Mary Carrington, Jacques Fellay, Tobias L Lenz
Genetic variation in the peptide-binding groove of the highly polymorphic HLA class I molecules has repeatedly been associated with HIV-1 control and progression to AIDS, accounting for up to 12% of the variation in HIV-1 set point viral load (spVL). This suggests a key role in disease control for HLA presentation of HIV-1 epitopes to cytotoxic T cells. However, a comprehensive understanding of the relevant HLA-bound HIV epitopes is still elusive. Here we describe a peptidome-wide association study (PepWAS) approach that integrates HLA genotypes and spVL data from 6,311 HIV-infected patients to interrogate the entire HIV-1 proteome (3,252 unique peptides) for disease-relevant peptides...
January 15, 2019: Proceedings of the National Academy of Sciences of the United States of America
Steven M Goodreau, Sarah E Stansfield, James T Murphy, Kathryn C Peebles, Geoffrey S Gottlieb, Neil F Abernethy, Joshua T Herbeck, John E Mittler
HIV viral load (VL) predicts both transmission potential and rate of disease progression. For reasons that are still not fully understood, the set point viral load (SPVL) established after acute infection varies across individuals and populations. Previous studies have suggested that population mean SPVL (MSPVL) has evolved near an optimum that reflects a trade-off between transmissibility and host survival. Sexual network structures affect rates of potential exposure during different within-host phases of infection marked by different transmission probabilities, and thus affect the number and timing of transmission events...
July 2018: Virus Evolution
Jiafeng Zhang, Ning Wang, Lin He, Xiaohong Pan, Xiaobei Ding
The alarming spread of HIV among men who have sex with men (MSM) has become a national concern in China. Estimating men's sexual HIV infectiousness from blood plasma viral load (BPVL) depends on the association between BPVL and semimal plasma viral load (SPVL). However, previous studies were controversial and few concentrated on MSM. Twenty antiretroviral therapy (ART) naive MSM and 54 MSM under ART were recruited between July and September 2015 in the city of Hangzhou, China. Blood and semen were collected in pairs at the same visit for each individual...
November 9, 2018: AIDS Research and Human Retroviruses
Sarah E Stansfield, John E Mittler, Geoffrey S Gottlieb, James T Murphy, Deven T Hamilton, Roger Detels, Steven M Wolinsky, Lisa P Jacobson, Joseph B Margolick, Charles R Rinaldo, Joshua T Herbeck, Steven M Goodreau
BACKGROUND: HIV-1 set point viral load (SPVL) is a highly variable trait that influences disease progression and transmission risk. Men who are exclusively insertive (EI) during anal intercourse require more sexual contacts to become infected than exclusively receptive (ER) men. Thus, we hypothesize that EIs are more likely to acquire their viruses from highly infectious partners (i.e., with high SPVLs) and to have higher SPVLs than infected ERs. METHODS: We used a one-generation Bernoulli model, a dynamic network model, and data from the Multicenter AIDS Cohort Study (MACS) to examine whether and under what circumstances MSM differ in SPVL by sexual role...
August 30, 2018: Epidemics
Marie-Laure Chaix, Faroudy Boufassa, Candice Meyzer, Marianne Leruez-Ville, Nadia Mahjoub, Marie-Laure Nere, Philippe Genet, Claudine Duvivier, Caroline Lascoux-Combes, Olivier Lambotte, Jade Ghosn
BACKGROUND: Whether spontaneous low levels of HIV-1 RNA in blood plasma correlate with low levels of HIV-1 RNA in seminal plasma has never been investigated in HIV controller (HIC) men so far. METHODS: HIC men enrolled in the ANRS CODEX cohort were eligible for the present study if they had no symptoms of sexually transmitted infections (STI). Two paired samples of blood and semen were collected four weeks apart. HIV-RNA was quantified in blood plasma (bpVL) and in seminal plasma (spVL), and cell-associated HIV-DNA was quantified in peripheral blood mononuclear cells (PBMC) and in non-sperm cells (NSC)...
2017: PloS One
Nadine Bachmann, Teja Turk, Claus Kadelka, Alex Marzel, Mohaned Shilaih, Jürg Böni, Vincent Aubert, Thomas Klimkait, Gabriel E Leventhal, Huldrych F Günthard, Roger Kouyos
BACKGROUND: Parent-offspring (PO) regression is a central tool to determine the heritability of phenotypic traits; i.e., the relative extent to which those traits are controlled by genetic factors. The applicability of PO regression to viral traits is unclear because the direction of viral transmission-who is the donor (parent) and who is the recipient (offspring)-is typically unknown and viral phylogenies are sparsely sampled. METHODS: We assessed the applicability of PO regression in a realistic setting using Ornstein-Uhlenbeck simulated data on phylogenies built from 11,442 Swiss HIV Cohort Study (SHCS) partial pol sequences and set-point viral load (SPVL) data from 3293 patients...
May 23, 2017: Retrovirology
B Richter, C Sänger, F Mussbach, H Scheuerlein, U Settmacher, U Dahmen
BACKGROUND: Current liver surgery includes complex multi-stage procedures such as portal vein ligation (PVL) followed by extended liver resection, especially in patients with Klatskin tumours. The risk for severe adhesions increases with every procedure. Finally, this complex sequence could fail because of malignant adhesions. Therefore, we proved the hypothesis of reducing malignant adhesions and increasing feasibility of a sequence with three hepato-biliary operations by implantation of a solid barrier...
October 2017: Journal of Visceral Surgery
Sang Woo Park, Benjamin M Bolker
Early in an epidemic, high densities of susceptible hosts select for relatively high parasite virulence; later in the epidemic, lower susceptible densities select for lower virulence. Thus over the course of a typical epidemic the average virulence of parasite strains increases initially, peaks partway through the epidemic, then declines again. However, precise quantitative outcomes, such as the peak virulence reached and its timing, may depend sensitively on epidemiological details. Fraser et al. proposed a model for the eco-evolutionary dynamics of HIV that incorporates the tradeoffs between transmission and virulence (mediated by set-point viral load, SPVL) and their heritability between hosts...
March 2017: PLoS Computational Biology
Elodie Valade, Naïm Bouazza, Gabrielle Lui, Silvia M Illamola, Sihem Benaboud, Jean-Marc Treluyer, Aurélie Cobat, Frantz Foissac, Maïlys De Sousa Mendes, Camille Chenevier-Gobeaux, Marie Suzan-Monti, Christine Rouzioux, Lambert Assoumou, Jean-Paul Viard, Saïk Urien, Jade Ghosn, Déborah Hirt
The aims of this study were to describe the blood plasma (BP) and seminal plasma (SP) pharmacokinetics of tenofovir (TFV) in HIV-1-infected men, to assess the role of genetic polymorphism in the variability of TFV transfer into the male genital tract, and to evaluate the impact of TFV SP exposure on seminal plasma HIV load (spVL). Men from the Evarist-ANRS EP 49 study treated with TFV as part of their antiretroviral therapy were included in the study. A total of 248 and 217 TFV BP and SP concentrations from 129 men were available for the analysis...
March 2017: Antimicrobial Agents and Chemotherapy
Katrina A Lythgoe, François Blanquart, Lorenzo Pellis, Christophe Fraser
The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models...
October 2016: PLoS Biology
Gabriel E Leventhal, Sebastian Bonhoeffer
In HIV patients, the set-point viral load (SPVL) is the most widely used predictor of disease severity. Yet SPVL varies over several orders of magnitude between patients. The heritability of SPVL quantifies how much of the variation in SPVL is due to transmissible viral genetics. There is currently no clear consensus on the value of SPVL heritability, as multiple studies have reported apparently discrepant estimates. Here we illustrate that the discrepancies in estimates are most likely due to differences in the estimation methods, rather than the study populations...
September 2016: Trends in Microbiology
Hannah E Roberts, Philip J R Goulder, Angela R McLean
In HIV-infected patients, an individual's set point viral load (SPVL) strongly predicts disease progression. Some think that SPVL is evolving, indicating that the virulence of the virus may be changing, but the data are not consistent. In addition, the widespread use of antiretroviral therapy (ART) has the potential to drive virulence evolution. We develop a simple deterministic model designed to answer the following questions: what are the expected patterns of virulence change in the initial decades of an epidemic? Could administration of ART drive changes in virulence evolution and, what is the potential size and direction of this effect? We find that even without ART we would not expect monotonic changes in average virulence...
December 6, 2015: Journal of the Royal Society, Interface
Anne Cori, Michael Pickles, Ard van Sighem, Luuk Gras, Daniela Bezemer, Peter Reiss, Christophe Fraser
BACKGROUND: CD4 cell count is a key measure of HIV disease progression, and the basis of successive international guidelines for treatment initiation. CD4 cell dynamics are used in mathematical and econometric models for evaluating public health need and interventions. Here, we estimate rates of CD4 decline, stratified by relevant covariates, in a form that is clinically transparent and can be directly used in such models. METHODS: We analyse the AIDS Therapy Evaluation in the Netherlands cohort, including individuals with date of seroconversion estimated to be within 1 year and with intensive clinical follow-up prior to treatment initiation...
November 28, 2015: AIDS
Elodie Valade, Jean-Marc Tréluyer, Silvia M Illamola, Naïm Bouazza, Frantz Foissac, Maïlys De Sousa Mendes, Gabrielle Lui, Camille Chenevier-Gobeaux, Marie Suzan-Monti, Christine Rouzioux, Lambert Assoumou, Jean-Paul Viard, Déborah Hirt, Saïk Urien, Jade Ghosn
We aimed to describe blood plasma (BP) and seminal plasma (SP) pharmacokinetics of emtricitabine (FTC) in HIV-1-infected men, assess its penetration in the male genital tract, and evaluate its impact on seminal plasma HIV load (spVL) detection. Men from the EVARIST ANRS EP49 study receiving combined antiretroviral therapy with FTC and with suppressed BP viral load were included in the study. A total of 236 and 209 FTC BP and SP concentrations, respectively, were available. A population pharmacokinetic model was developed with Monolix 4...
November 2015: Antimicrobial Agents and Chemotherapy
Joshua T Herbeck, John E Mittler, Geoffrey S Gottlieb, James I Mullins
Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL) as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions...
June 2014: PLoS Computational Biology
Jade Ghosn, Marianne Leruez-Ville, Jérôme Blanche, Aurore Delobelle, Céline Beaudoux, Laurence Mascard, Hervé Lecuyer, Ana Canestri, Roland Landman, David Zucman, Diane Ponscarme, Agathe Rami, Jean-Paul Viard, Bruno Spire, Christine Rouzioux, Dominique Costagliola, Marie Suzan-Monti
BACKGROUND: Few data exist on the efficacy of combined antiretroviral therapy (cART) in semen of human immunodeficiency virus type 1 (HIV-1) infected men who have sex with men (MSM) with sustained control of HIV replication in blood. METHODS: HIV-1 infected MSM on successful cART for >6 months were enrolled. HIV-RNA was quantified in seminal plasma (spVL) and in blood plasma (bpVL) from 2 paired samples collected 4 weeks apart. Relationship between spVL and bpVL (measured by an ultrasensitive assay, LOQ 10 copies/mL), total peripheral blood mononuclear cells (PBMC)-associated HIV-DNA, sexually transmitted infections (STIs), and self-reported socio-behavioral characteristics was assessed using GEE logistic regression...
June 2014: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
George Shirreff, Samuel Alizon, Anne Cori, Huldrych F Günthard, Oliver Laeyendecker, Ard van Sighem, Daniela Bezemer, Christophe Fraser
BACKGROUND AND OBJECTIVES: The severity of HIV-1 infection, measured by set-point viral load (SPVL), is highly variable between individuals. Its heritability between infections quantifies the control the pathogen genotype has over disease severity. Heritability estimates vary widely between studies, but differences in methods make comparison difficult. Phylogenetic comparative analysis offers measures of phylogenetic signal, but it is unclear how to interpret them in terms of the fraction of variance in SPVL controlled by the virus genotype...
January 2013: Evolution, Medicine, and Public Health
Anna Hool, Gabriel E Leventhal, Sebastian Bonhoeffer
The asymptomatic phase of HIV-1 infections is characterised by a stable set-point viral load (SPVL) within patients. The SPVL is a strong predictor of disease progression and shows considerable variation of multiple orders of magnitude between patients. Recent studies have found that the SPVL in donor and recipient pairs is strongly correlated indicating that the virus genotype strongly influences viral load. Viral genetic factors that increase both viral load and the replicative capacity of the virus would result in rapid within-host evolution to higher viral loads...
December 2013: Epidemics
D J Chan
To estimate the impact of sexual practices and HIV-1 viral load status on HIV-1 incidence, we surveyed 38 men who have sex with men (MSM) on their sexual practices in the past three months. HIV-1 RNA load was measured in semen and blood contemporaneously. A Bernoulli model was developed incorporating seminal plasma viral load (SPVL), number and serostatus of partners, and number of protected and unprotected episodes of anal intercourse. Probability of transmission according to SPVL was determined by sensitivity analysis based on the correlation between blood plasma viral load (BPVL) and SPVL...
October 2012: International Journal of STD & AIDS
Diego F Cuadros, Gisela García-Ramos
BACKGROUND: Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL...
2012: Theoretical Biology & Medical Modelling
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