SPVL

Pathogens face a tradeoff with respect to virulence; while more virulent strains often have higher per-contact transmission rates, they are also more likely to kill their hosts earlier. Because virulence is a heritable trait, there is concern that a disease-modifying vaccine, which reduces the disease severity of an infected vaccinee without changing the underlying pathogen genotype, may result in the evolution of higher pathogen virulence. We explored the potential for such virulence evolution with a disease-modifying HIV-1 vaccine in an agent-based stochastic epidemic model of HIV in United States men who have sex with men (MSM)...

Biological sex and host genetics influence HIV pathogenesis. Females have a higher likelihood of spontaneous viral control and lower setpoint viral load (spVL). No prior studies have assessed sex-specific genetics of HIV. To address this, we performed a sex stratified genome-wide association study using data from the International Collaboration for the Genomics of HIV. Although it is the largest collection of genomic data in HIV, this multi-ethnic sample of 9,705 people is 81.3% male. We sought to identify sex-specific genetic variants and genes associated with HIV spVL and control...

BACKGROUND: Set-point viral load (SPVL) correlates with the age at which people acquire HIV. Although immunosenescence may seem like a parsimonious explanation for this, it does not easily explain the observation that the relationship between age and SPVL attenuates when accounting for source partner SPVL. Here we propose an alternative explanation that encompasses this latter finding: that decreasing risk of acquisition with older age generates a selection bottleneck that selects for more virulent strains with age...

Background and Aims: Patients with malignant biliary obstruction do not seem to benefit from "two-stage hepatectomy" due to an impairment of liver regeneration. We designed a novel model of "repeated regeneration stimuli" in rats mimicking a "two-stage hepatectomy" with selective or complete biliary occlusion mimicking Klatskin tumors III° or IV°. Using this new model, we wanted to investigate (1) the impact of preexistent cholestasis of different extent on the time course of liver regeneration and (2) the dynamics of hepatobiliary remodeling under regeneration conditions...

Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 104 and 105 copies of viral RNA per ml. Here we aimed to detect transmission fitness differences between viruses from individuals with different SPVLs directly from phylogenetic trees inferred from whole-genome sequences. We used the local branching index (LBI) as a proxy for transmission fitness...

HIV viral load (VL) is an important predictor of HIV progression and transmission. Anti-retroviral therapy (ART) has been reported to reduce HIV transmission by lowering VL. However, apart from this beneficial effect, increased levels of population mean set-point viral load (SPVL), an estimator for HIV virulence, have been observed in men who have sex with men (MSM) in the decade following the introduction of ART in The Netherlands. Several studies have been devoted to explain these counter-intuitive trends in SPVL...

HIV set point viral load (SPVL), the viral load established shortly after initial infection, is a proxy for HIV virulence: higher SPVLs lead to higher risk of transmission and faster disease progression. Three models of test-and-treat scenarios, mainly in heterosexual populations, found that increasing treatment coverage selected for more virulent viruses. We modeled virulence evolution in a population of men who have sex with men (MSM) with increasing test-and-treat coverage. We extended a stochastic, dynamic network model (EvoNetHIV)...

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB...

The paired auditory organ of mosquito, the Johnston's organ (JO), being the receiver of particle velocity component of sound, is directional by its structure. However, to date almost no physiological measurements of its directionality was done. In addition, the recent finding on the grouping of the JO auditory neurons into the antiphase pairs demanded confirmation by different methods. Using the vector superposition of the signals produced by two orthogonally oriented speakers, we measured the directional characteristics of individual units as well as their relations in physiologically distinguishable groups - pairs or triplets...

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...

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...

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...

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...

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)...

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...

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...

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...

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...

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...

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...