scholarly journals The impact of HIV-1 within-host evolution on transmission dynamics

2017 ◽  
Author(s):  
Kristof Theys ◽  
Pieter Libin ◽  
Andrea-Clemencia Pineda-Pena ◽  
Ann Nowe ◽  
Anne-Mieke Vandamme ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Epidemiological Studies ◽  
Transmission Efficiency ◽  
Evolutionary Rates ◽  
New Host ◽  
Trade Off ◽  
Host Immune Responses ◽  
Host Evolution ◽  
The Impact ◽  
Hiv 1

AbstractThe adaptive potential of HIV-1 is a vital mechanism to evade host immune responses and antiviral treatment. However, high evolutionary rates during persistent infection can impair transmission efficiency and alter disease progression in the new host, resulting in a delicate trade-off between within-host virulence and between-host infectiousness. This trade-off is visible in the disparity in evolutionary rates at within-host and between-host levels, and preferential transmission of ancestral donor viruses. Understanding the impact of within-host evolution for epidemiological studies is essential for the design of preventive and therapeutic measures. Herein, we review recent theoretical and experimental work that generated new insights into the complex link between within-host evolution and between-host fitness, revealing temporal and selective processes underlying the structure and dynamics of HIV-1 transmission.

scholarly journals Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Flaminia Olearo ◽  
Huyen Nguyen ◽  
Fabrice Bonnet ◽  
Sabine Yerly ◽  
Gilles Wandeler ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Antiviral Treatment ◽  
Composite Endpoint ◽  
Hiv Treatment ◽  
Hiv Positive ◽  
Prior History ◽  
History Of ◽  
The Impact ◽  
Hiv 1

Abstract Objective The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. Method This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population. Results We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154–441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2–79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4–21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35–4.59 and HR 1.66; 95% CI, 0.81–3.43, respectively). Conclusions In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.

scholarly journals An evolutionary-based approach to quantify the genetic barrier to drug resistance in fast-evolving viruses: an application to HIV-1 subtypes and integrase inhibitors

2019 ◽  
Author(s):  
Kristof Theys ◽  
Pieter Libin ◽  
Kristel Van Laethem ◽  
Ana B Abecasis
Keyword(s):  
Drug Resistance ◽  
Antiviral Treatment ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Genetic Barrier ◽  
Viral Pathogens ◽  
Subtype B ◽  
Genetic Potential ◽  
The Impact ◽  
Hiv 1

AbstractViral pathogens causing global disease burdens are often characterised by high rates of evolutionary changes, facilitating escape from therapeutic or immune selective pressure. Extensive viral diversity at baseline can shorten the time to resistance emergence and alter mutational pathways, but the impact of genotypic background on the genetic barrier can be difficult to capture, in particular for antivirals in experimental stages, recently approved or expanded into new settings. We developed an evolutionary-based counting method to quantify the population genetic potential to resistance and assess differences between populations. We demonstrate its applicability to HIV-1 integrase inhibitors, as their increasing use globally contrasts with limited availability of non-B subtype resistant sequences and corresponding knowledge gap on drug resistance. A large sequence dataset encompassing most prevailing subtypes and resistance mutations of first- and second-generation inhibitors were investigated. A varying genetic potential for resistance across HIV-1 subtypes was detected for 15 mutations at 12 positions, with notably 140S in subtype B, while 140C was discarded to vary across subtypes. An additional analysis for HIV-1 reverse transcriptase inhibitors identified a higher potential for 65R in subtype C, on the basis of a differential codon usage not reported before. The evolutionary interpretation of genomic differences for antiviral treatment remains challenging. Our framework advances existing counting methods with an increased sensitivity that identified novel subtype dependencies as well as rejected previous statements. Future applications include novel HIV-1 drug classes as well as other viral pathogens.

scholarly journals Acquired immune heterogeneity and its sources in human helminth infection

Parasitology ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 139-159 ◽  
Author(s):  
C. D. BOURKE ◽  
R. M. MAIZELS ◽  
F. MUTAPI
Keyword(s):  
Immune Responses ◽  
Large Scale ◽  
Antigen Expression ◽  
Epidemiological Studies ◽  
Public Health Importance ◽  
Host Immune Responses ◽  
Parasitic Worm ◽  
Acquired Immune Responses ◽  
The Impact

SUMMARYSimilarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recentin vitroand immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigensin utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

scholarly journals The impact of HIV-1 within-host evolution on transmission dynamics

2018 ◽  
Vol 28 ◽  
pp. 92-101 ◽  
Author(s):  
Kristof Theys ◽  
Pieter Libin ◽  
Andrea-Clemencia Pineda-Peña ◽  
Ann Nowé ◽  
Anne-Mieke Vandamme ◽  
...  
Keyword(s):  
Transmission Dynamics ◽  
Host Evolution ◽  
The Impact ◽  
Hiv 1

scholarly journals Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression

2016 ◽  
Vol 213 (10) ◽  
pp. 2049-2063 ◽  
Author(s):  
Daniela C. Mónaco ◽  
Dario A. Dilernia ◽  
Andrew Fiore-Gartland ◽  
Tianwei Yu ◽  
Jessica L. Prince ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Progression ◽  
Major Determinant ◽  
Immune Recognition ◽  
Multivariable Model ◽  
Viral Control ◽  
New Host ◽  
Set Point ◽  
The Impact ◽  
Hiv 1

HIV-1 adapts to a new host through mutations that facilitate immune escape. Here, we evaluate the impact on viral control and disease progression of transmitted polymorphisms that were either preadapted to or nonassociated with the new host’s HLA. In a cohort of 169 Zambian heterosexual transmission pairs, we found that almost one-third of possible HLA-linked target sites in the transmitted virus Gag protein are already adapted, and that this transmitted preadaptation significantly reduced early immune recognition of epitopes. Transmitted preadapted and nonassociated polymorphisms showed opposing effects on set-point VL and the balance between the two was significantly associated with higher set-point VLs in a multivariable model including other risk factors. Transmitted preadaptation was also significantly associated with faster CD4 decline (<350 cells/µl) and this association was stronger after accounting for nonassociated polymorphisms, which were linked with slower CD4 decline. Overall, the relative ratio of the two classes of polymorphisms was found to be the major determinant of CD4 decline in a multivariable model including other risk factors. This study reveals that, even before an immune response is mounted in the new host, the balance of these opposing factors can significantly influence the outcome of HIV-1 infection.

scholarly journals Disentangling the impact of within-host evolution and transmission dynamics on the tempo of HIV-1 evolution

AIDS ◽  
2015 ◽  
Vol 29 (12) ◽  
pp. 1549-1556 ◽  
Author(s):  
Bram Vrancken ◽  
Guy Baele ◽  
Anne-Mieke Vandamme ◽  
Kristel van Laethem ◽  
Marc A. Suchard ◽  
...  
Keyword(s):  
Transmission Dynamics ◽  
Host Evolution ◽  
The Impact ◽  
Hiv 1

Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Pregnant Women ◽  
Disease Severity ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
Severe Influenza ◽  
The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

scholarly journals Detection of diarrhoea associated rotavirus and co-infection with diarrhoeagenic pathogens in the Littoral region of Cameroon using ELISA, RT-PCR and Luminex xTAG GPP assays

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rahinatou N. Ghapoutsa ◽  
Maurice Boda ◽  
Rashi Gautam ◽  
Valantine Ngum Ndze ◽  
Akongnwi E. Mugyia ◽  
...  
Keyword(s):  
Demographic Data ◽  
Laboratory Diagnosis ◽  
Epidemiological Studies ◽  
Sub Saharan Africa ◽  
Rt Pcr ◽  
Mortality And Morbidity ◽  
Vaccine Introduction ◽  
Littoral Region ◽  
Rotavirus Vaccines ◽  
The Impact

Abstract Background Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases. Methods We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay. Results The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix. Conclusion This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children.

scholarly journals The Impact of Work Hours on Depressive Symptoms among Koreans Aged 45 and Over

2021 ◽  
Vol 18 (3) ◽  
pp. 853
Author(s):  
Juyeong Kim ◽  
Eun-Cheol Park
Keyword(s):  
Older Adults ◽  
Depressive Symptoms ◽  
Social Services ◽  
Depression Scale ◽  
Epidemiological Studies ◽  
Work Hours ◽  
Middle Aged ◽  
Health Studies ◽  
Males And Females ◽  
The Impact

Background: Given the documented importance of employment for middle-aged and older adults’ mental health, studies of the association between their number of work hours and depressive symptoms are needed. Objectives: To examine the association between the number of work hours and depressive symptoms in Korean aged 45 and over. Methods: We used data from the first wave to fourth wave of the Korea Longitudinal Study of Aging. Using the first wave at baseline, data included 9845 individuals. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression scale. We performed a longitudinal analysis to estimate the prevalence of depressive symptoms by work hours. Results: Both unemployed males and females aged 45–65 years were associated with higher depressive symptoms (β = 0.59, p < 0.001; β = 0.32, p < 0.001). Females working ≥ 69 h were associated with higher depressive symptoms compared to those working 41–68 h (β = 0.25, p = 0.013). Among those both middle-aged and older adults, both males and females unemployed were associated with higher depressive symptoms. Those middle-aged female working ≥69 h were associated with higher depressive symptoms. Conclusions: An increase in depressive symptoms was associated with unemployed males and females working ≥69 h compared to those working 41–68 h. Although this association was found among middle-aged individuals, a decrease in depressive symptoms in both sexes was associated with working 1–40 h. Depressive symptoms should decrease by implementing employment policies and social services to encourage employers to support middle-aged and older adults in the workforce considering their sex and age differences.

scholarly journals STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lorena Leticia Peixoto de Lima ◽  
Allysson Quintino Tenório de Oliveira ◽  
Tuane Carolina Ferreira Moura ◽  
Ednelza da Silva Graça Amoras ◽  
Sandra Souza Lima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Α Level ◽  
The Impact ◽  
Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

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