scholarly journals Mycobacterium tuberculosis co-infection is associated with increased surrogate marker of the HIV reservoir

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Jingna Xun ◽  
Tangkai Qi ◽  
Lei Zou ◽  
Qi Tang ◽  
Yinzhong Shen ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Surrogate Marker ◽  
Baseline Viral Load ◽  
People Living With Hiv ◽  
Peripheral Blood Mononuclear ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Interleukin 7 ◽  
Living With Hiv ◽  
The Impact

Abstract Background Tuberculosis (Tb) is the most frequent opportunistic infection among people living with HIV infection. The impact of Tb co-infection in the establishment and maintenance of the HIV reservoir is unclear. Method We enrolled 13 HIV-infected patients with microbiologically confirmed Tb and 10 matched mono-HIV infected controls. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), plasma interleukin-7 (IL-7) concentrations and the activities of indoleamine 2,3-dioxygenase (IDO) were measured for all the participants prior to therapy and after antiretroviral therapy (ART). Results After a duration of 16 (12, 22) months’ ART, patients co-infected with Tb who were cured of Tb maintained higher levels of HIV DNA compared with mono-HIV infected patients [2.89 (2.65- 3.05) log10 copies/106 cells vs. 2.30 (2.11–2.84) log10 copies/106 cells, P = 0.008]. The levels of on-ART HIV DNA were positively correlated with the baseline viral load (r = 0.64, P = 0.02) in Tb co-infected group. However, neither plasma IL-7 concentration nor plasma IDO activity was correlated with the level of on-ART HIV DNA. Conclusions Tb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.

scholarly journals Initiating antiretroviral treatment early in infancy has long-term benefits on the HIV reservoir in late childhood and adolescence

2021 ◽  
Author(s):  
Véronique Avettand-Fenoel ◽  
Jérôme Lechenadec ◽  
Mariama Sadjo Diallo ◽  
Marine Fillion ◽  
Adeline Melard ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Ex Vivo ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Childhood And Adolescence ◽  
Older Children ◽  
Peripheral Blood Mononuclear ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Cart Initiation

Abstract Background Early combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study aims to compare HIV reservoirs in children (5-12 years) and adolescents (13-17 years) who started cART before 6 months (early (E-)group) or after 2 years old (late (L-)group). Methods The ANRS-EP59-CLEAC study prospectively enrolled 76 HIV-1 perinatally-infected patients who reached HIV-RNA<400 copies/mL less than 24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cells (PBMCs) stimulation. Results Total HIV-DNA levels were lower in early- than late-treated patients (Children: 2.14 vs 2.87 log cp/million PBMCs, p<0.0001; Adolescents: 2.25 vs 2.74log, p<0.0001). Low reservoir was independently associated with treatment precocity, protective HLA and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than the other patients (4 vs 54 months, p=0.03). In those with sustained virological control, transitional memory and effector memory CD4+T cells were less infected in the E-group than in the L-group (p=0.03 and 0.02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between the groups. Conclusions Early cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies.

scholarly journals Molecular characterization of atherosclerosis in HIV positive persons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Cornwell ◽  
Rohith Palli ◽  
Meera V. Singh ◽  
Lauren Benoodt ◽  
Alicia Tyrell ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Regulatory Networks ◽  
Target Genes ◽  
Mononuclear Cells ◽  
People Living With Hiv ◽  
Data Types ◽  
Peripheral Blood Mononuclear ◽  
Bicarbonate Transporter ◽  
Persons Living With Hiv ◽  
Living With Hiv

AbstractPeople living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we further assessed miRNA expression in PBMCs of a subset of 12 HIV+ people with and without atherosclerosis. We identified 12 miRNAs differentially expressed between HIV+ AS+ and HIV+ , and validated 5 of those by RT-qPCR. While a few of these miRNAs have been implicated in HIV and atherosclerosis, others are novel. Integrating miRNA measurements with mRNA, we identified 27 target genes including SLC4A7, a critical sodium and bicarbonate transporter, that are potentially dysregulated during atherosclerosis. Additionally, we uncovered that levels of plasma cytokines were associated with transcription factor activity and miRNA expression in PBMCs. For example, BACH2 activity was associated with IL-1β, IL-15, and MIP-1α. IP10 and TNFα levels were associated with miR-124-3p. Finally, integration of all data types into a single network revealed increased importance of miRNAs in network regulation of the HIV+ group in contrast with increased importance of cytokines in the HIV+ AS+ group.

scholarly journals Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection

2019 ◽  
Vol 20 (18) ◽  
pp. 4476 ◽  
Author(s):  
Manuel G. Feria-Garzón ◽  
María T. Rugeles ◽  
Juan C. Hernandez ◽  
Jorge A. Lujan ◽  
Natalia A. Taborda
Keyword(s):  
Mononuclear Cells ◽  
Molecular Complexes ◽  
Inhibitory Effect ◽  
Inflammasome Activation ◽  
People Living With Hiv ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Gastrointestinal Tissue ◽  
Living With Hiv ◽  
Hiv 1

Background: HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1β and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis. Objective: To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors. Methods: PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1β and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β, and IL-18 were quantified. Results: Cells treated with SSZ exhibited a decreased IL-1β production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1β was positively correlated with the CD4+ T-cell count and negatively with the viral load. Conclusion: Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status.

scholarly journals “[It] is now my responsibility to fulfill that wish:” Clinical and rapid autopsy staff members’ experiences and perceptions of HIV reservoir research at the end of life

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242420
Author(s):  
Kelly E. Perry ◽  
Jeff Taylor ◽  
Hursch Patel ◽  
Sogol Stephanie Javadi ◽  
Kushagra Mathur ◽  
...  
Keyword(s):  
Focus Group ◽  
End Of Life ◽  
Scale Up ◽  
People Living With Hiv ◽  
Autopsy Study ◽  
Hiv Reservoir ◽  
Staff Members ◽  
Rapid Autopsy ◽  
Living With Hiv ◽  
The Impact

Introduction Little is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members’ perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research. Methods Two focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years. Results Qualitative focus group data revealed five major themes underlying study staff members’ multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants’ altruism, fulfillment, and control at the end of life, 2) perceptions of staff members’ close involvement in the Last Gift study, with sub-themes related to staff members’ cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites. Discussion Understanding staff members’ nuanced emotional and procedural experiences is crucial to the Last Gift study’s sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study’s potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV.

scholarly journals Consequences of COVID-19 crisis for persons with HIV: the impact of social determinants of health

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristie C. Waterfield ◽  
Gulzar H. Shah ◽  
Gina D. Etheredge ◽  
Osaremhen Ikhile
Keyword(s):  
Public Health ◽  
Health Care ◽  
Clinical Care ◽  
Hiv Infections ◽  
People Living With Hiv ◽  
Negative Consequences ◽  
Persons Who Inject Drugs ◽  
Persons Living With Hiv ◽  
Living With Hiv ◽  
The Impact

Abstract Background With the indiscriminate spread of COVID-19 globally, many populations are experiencing negative consequences such as job loss, food insecurity, and inability to manage existing medical conditions and maintain preventive measures such as social distancing and personal preventative equipment. Some of the most disadvantaged in the COVID-19 era are people living with HIV/AIDS and other autoimmune diseases. Discussion As the number of new HIV infections decrease globally, many subpopulations remain at high risk of infection due to lack of or limited access to prevention services, as well as clinical care and treatment. For persons living with HIV or at higher risk of contracting HIV, including persons who inject drugs or men that have sex with men, the risk of COVID-19 infection increases if they have certain comorbidities, are older than 60 years of age, and are homeless, orphaned, or vulnerable children. The risk of COVID-19 is also more significant for those that live in Low- and Middle-Income Countries, rural, and/or poverty-stricken areas. An additional concern for those living the HIV is the double stigma that may arise if they also test positive for COVID-19. As public health and health care workers try to tackle the needs of the populations that they serve, they are beginning to realize the need for a change in the infrastructure that will include more efficient partnerships between public health, health care, and HIV programs. Conclusion Persons living with HIV that also have other underlying comorbidities are a great disadvantage from the negative consequences of COVID-19. For those that may test positive for both HIV and COVID-19, the increased psychosocial burdens stemming from stress and isolation, as well as, experiencing additional barriers that inhibit access to care, may cause them to become more disenfranchised. Thus, it becomes very important during the current pandemic for these challenges and barriers to be addressed so that these persons living with HIV can maintain continuity of care, as well as, their social and mental support systems.

scholarly journals Regulation of CTLA-4 and PD-L1 Expression in Relapsing-Remitting Multiple Sclerosis Patients after Treatment with Fingolimod, IFNβ-1α, Glatiramer Acetate, and Dimethyl Fumarate Drugs

2021 ◽  
Vol 11 (8) ◽  
pp. 721
Author(s):  
Afshin Derakhshani ◽  
Zahra Asadzadeh ◽  
Hossein Safarpour ◽  
Patrizia Leone ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Immune Checkpoints ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
The Impact

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that is characterized by inflammation which typically results in significant impairment in most patients. Immune checkpoints act as co-stimulatory and co-inhibitory molecules and play a fundamental role in keeping the equilibrium of the immune system. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and Programmed death-ligand 1 (PD-L1), as inhibitory immune checkpoints, participate in terminating the development of numerous autoimmune diseases, including MS. We assessed the CTLA-4 and PD-L1 gene expression in the different cell types of peripheral blood mononuclear cells of MS patients using single-cell RNA-seq data. Additionally, this study outlines how CTLA-4 and PD-L1 expression was altered in the PBMC samples of relapsing-remitting multiple sclerosis (RRMS) patients compared to the healthy group. Finally, it investigates the impact of various MS-related treatments in the CTLA-4 and PD-L1 expression to restrain autoreactive T cells and stop the development of MS autoimmunity.

scholarly journals Free access to antiretroviral treatment and protection against the risk of catastrophic health expenditure in people living with HIV: evidence from Cameroon

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marwân-al-Qays Bousmah ◽  
Marie Libérée Nishimwe ◽  
Christopher Kuaban ◽  
Sylvie Boyer
Keyword(s):  
Socioeconomic Status ◽  
Health Expenditure ◽  
Antiretroviral Treatment ◽  
Catastrophic Health Expenditure ◽  
Hiv Care ◽  
Free Access ◽  
People Living With Hiv ◽  
Art Policy ◽  
Living With Hiv ◽  
The Impact

Abstract Background To foster access to care and reduce the burden of health expenditures on people living with HIV (PLHIV), several sub-Saharan African countries, including Cameroon, have adopted a policy of removing HIV-related fees, especially for antiretroviral treatment (ART). We investigate the impact of Cameroon’s free antiretroviral treatment (ART) policy, enacted in May 2007, on catastrophic health expenditure (CHE) risk according to socioeconomic status, in PLHIV enrolled in the country’s treatment access program. Methods Based on primary data from two cross-sectional surveys of PLHIV outpatients in 2006–2007 and 2014 (i.e., before and after the policy’s implementation, respectively), we used inverse propensity score weighting to reduce covariate imbalances between participants in both surveys, combined with probit regressions of CHE incidence. The analysis included participants treated with ART in one of the 11 HIV services common to both surveys (n = 1275). Results The free ART policy was associated with a significantly lower risk of CHE only in the poorest PLHIV while no significant effect was found in lower-middle or upper socioeconomic status PLHIV. Unexpectedly, the risk of CHE was higher in those with middle socioeconomic status after the policy’s implementation. Conclusions Our findings suggest that Cameroon’s free ART policy is pro-poor. As it only benefitted PLHIV with the lowest socioeconomic status, increased comprehensive HIV care coverage is needed to substantially reduce the risk of CHE and the associated risk of impoverishment for all PLHIV.

scholarly journals Vaccine responses in ageing and chronic viral infection

2021 ◽  
Author(s):  
Chloe Rees-Spear ◽  
Laura E McCoy
Keyword(s):  
Viral Infections ◽  
The Elderly ◽  
People Living With Hiv ◽  
Chronic Infections ◽  
Vaccine Responses ◽  
Inflammatory Conditions ◽  
Immunological Changes ◽  
Cellular Responsiveness ◽  
Living With Hiv ◽  
The Impact

Abstract Lay Summary Improved life expectancy in recent years has led to a growing population of adults over the age of 60. Age is commonly associated with increased inflammatory conditions and infections. Similar immunological changes have been observed during chronic infections, in particular HIV, where this is compounded by the success of antiretroviral therapy that has increased the number of people living with HIV into their sixties and beyond. The increased susceptibility of these groups to infection makes vaccination all the more important. However, the alterations to their immune systems call into question how effective those vaccinations may be. Here we discuss vaccine efficacy within elderly and chronically infected populations and investigate the immunological changes that may impact vaccine responsiveness. Over the last few decades, changing population demographics have shown that there is a growing number of individuals living past the age of 60. With this expanding older population comes an increase in individuals that are more susceptible to chronic illness and disease. An important part of maintaining health in this population is through prophylactic vaccination, however, there is growing evidence that vaccines may be less effective in the elderly. Furthermore, with the success of anti-viral therapies, chronic infections such as HIV are becoming increasingly prevalent in older populations and present a relatively unstudied population with respect to the efficacy of vaccination. Here we will examine the evidence for age-associated reduction in antibody and cellular responsiveness to a variety of common vaccines, and investigate the underlying causes attributed to this phenomenon, such as inflammation and senescence. We will also discuss the impact of chronic viral infections on immune responses in both young and elderly patients, particularly those living with HIV, and how this affects vaccinations in these populations.

scholarly journals Stigma, gay men and biomedical prevention: the challenges and opportunities of a rapidly changing HIV prevention landscape

Sexual Health ◽  
2017 ◽  
Vol 14 (1) ◽  
pp. 111 ◽  
Author(s):  
Graham Brown ◽  
William Leonard ◽  
Anthony Lyons ◽  
Jennifer Power ◽  
Dirk Sander ◽  
...  
Keyword(s):  
Hiv Prevention ◽  
Gay Men ◽  
Sexual Minorities ◽  
Research Policy ◽  
Scale Up ◽  
People Living With Hiv ◽  
Structural Level ◽  
Biomedical Technologies ◽  
Living With Hiv ◽  
The Impact

Improvements in biomedical technologies, combined with changing social attitudes to sexual minorities, provide new opportunities for HIV prevention among gay and other men who have sex with men (GMSM). The potential of these new biomedical technologies (biotechnologies) to reduce HIV transmission and the impact of HIV among GMSM will depend, in part, on the degree to which they challenge prejudicial attitudes, practices and stigma directed against gay men and people living with HIV (PLHIV). At the structural level, stigma regarding gay men and HIV can influence the scale-up of new biotechnologies and negatively affect GMSM’s access to and use of these technologies. At the personal level, stigma can affect individual gay men’s sense of value and confidence as they negotiate serodiscordant relationships or access services. This paper argues that maximising the benefits of new biomedical technologies depends on reducing stigma directed at sexual minorities and people living with HIV and promoting positive social changes towards and within GMSM communities. HIV research, policy and programs will need to invest in: (1) responding to structural and institutional stigma; (2) health promotion and health services that recognise and work to address the impact of stigma on GMSM’s incorporation of new HIV prevention biotechnologies; (3) enhanced mobilisation and participation of GMSM and PLHIV in new approaches to HIV prevention; and (4) expanded approaches to research and evaluation in stigma reduction and its relationship with HIV prevention. The HIV response must become bolder in resourcing, designing and evaluating programs that interact with and influence stigma at multiple levels, including structural-level stigma.

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