scholarly journals Pre-cART Immune Parameters in People Living With HIV Might Help Predict CD8+ T-Cell Characteristics, Inflammation Levels, and Reservoir Composition After Effective cART

2021 ◽  
Vol 6 (2) ◽  
pp. 60-89
Author(s):  
Jimena Salido ◽  
Alejandro Czernikier ◽  
Cesar Trifone ◽  
María Laura Polo ◽  
María Ines Figueroa ◽  
...  

Background: Combined antiretroviral treatment (cART) for HIV infection is highly effective in controlling viral replication. However, it cannot achieve a sterilizing cure.  Several strategies have been proposed to achieve a functional cure, some of them based on immune-mediated clearing of persistently infected cells. Here, we aimed at identifying factors related to CD8TC and CD4TC quality before cART initiation that associate with the persistence of CD8TC antiviral response after cART, inflammation levels, and the size of the viral reservoir. Methods: Samples from 25 persons living with HIV were obtained before and after (15 months) cART initiation. Phenotype and functionality of bulk and HIV-specific T cells were assayed by flow cytometry ex vivo or after expansion in pre-cART or post-cART samples, respectively. Cell-Associated (CA) HIV DNA (total and integrated) and RNA (unspliced [US] and multiple spliced [MS]) were quantitated by real-time PCR on post-cART samples. Post-cART plasma levels of CXCL10 (IP-10), soluble CD14 (sCD14) and soluble CD163 (sCD163) were measured by ELISA.  Results: Pre-cART phenotype of CD8TCs and magnitude and phenotype of HIV-specific response correlated with the phenotype and functionality of CD8TCs post-cART. Moreover, the phenotype of the CD8TCs pre-cART correlated with markers of HIV persistence and inflammation post-cART. Finally, exhaustion and differentiation of CD4TCs pre-cART were associated with the composition of the HIV reservoir post-cART and the level of inflammation. Conclusions: Overall, this work provides data to help understand and identify parameters that could be used as markers in the development of immune-based functional HIV cure strategies.

Author(s):  
Jennifer Jao ◽  
Lauren C Balmert ◽  
Shan Sun ◽  
Grace A McComsey ◽  
Todd T Brown ◽  
...  

Abstract Context Disentangling contributions of HIV from antiretroviral therapy (ART) and understanding the effects of different ART on metabolic complications in persons living with HIV (PLHIV) has been challenging. Objective We assessed the effect of untreated HIV infection as well as different antiretroviral therapy (ART) on the metabolome/lipidome. Methods Widely targeted plasma metabolomic and lipidomic profiling was performed on HIV-seronegative individuals and people living with HIV (PLHIV) before and after initiating ART (tenofovir/emtricitabine plus atazanavir/ritonavir [ATV/r] or darunavir/ritonavir [DRV/r] or raltegravir [RAL]). Orthogonal partial least squares discriminant analysis was used to assess metabolites/lipid subspecies that discriminated between groups. Graphical lasso estimated group-specific metabolite/lipid subspecies networks associated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Correlations between inflammatory markers and metabolites/lipid subspecies were visualized using heat maps. Results Of 435 participants, 218 were PLHIV. Compared to HIV-seronegative individuals, ART-naive PLHIV exhibited higher levels of saturated triacylglycerols/triglycerides (TAGs) and 3-hydroxy-kynurenine, lower levels of unsaturated TAGs and N-acetyl-tryptophan, and a sparser and less heterogeneous network of metabolites/lipid subspecies associated with HOMA-IR. PLHIV on RAL vs ATV/r or DRV/r had lower saturated and unsaturated TAGs. Positive correlations were found between medium-long chain acylcarnitines (C14-C6 ACs), palmitate, and HOMA-IR for RAL but not ATV/r or DRV/r. Stronger correlations were seen for TAGs with interleukin 6 and high-sensitivity C-reactive protein after RAL vs ATV/r or DRV/r initiation; these correlations were absent in ART-naive PLHIV. Conclusion Alterations in the metabolome/lipidome suggest increased lipogenesis for ART-naive PLHIV vs HIV-seronegative individuals, increased TAG turnover for RAL vs ATV/r or DRV/r, and increased inflammation associated with this altered metabolome/lipidome after initiating ART. Future studies are needed to understand cardiometabolic consequences of lipogenesis and inflammation in PLHIV.


2015 ◽  
Vol 1 (1) ◽  
pp. 1-10
Author(s):  
Jit B. Darnal ◽  
Pawinee Doung-ngern ◽  
Lungten Z. Wangchuk ◽  
Mongal S. Gurung ◽  
Witaya Swaddiwudhipong

Introduction: A total of 217 HIV positive cases have been reported in Bhutan as of 2010. A descriptive study toassess the knowledge and behavioral practices among 116 of those persons living with HIV (PLHIV) was conducted in 2011. Methods: Data on demographic characteristics, sexual behavior, alcohol consumption: mobility and HIVknowledge both before and after testing positive for HIV were collected. Responses regarding behavior before and after HIV diagnosis were compared. Results: Of 116 participants, 52.6% were males; a majority of male PLHIV (72.1%) belonged to salaried group of people while housewife represented 47.3% among female respondents. Fortythree percent of male and 5.5% of female participants reported having exchange sex and 52.5% of male and 41.8% of female participants reported having non-exchange sex partners before HIV diagnosis. The consistent condom use had significantly increased after HIV diagnosis among males with exchange (12% vs. 60%, p=.04) and non-exchange (13% vs. 100%, p<.001) partners. Eighty-four percent of male and 61.8% of female participants reported consuming alcohol before HIV diagnosis. Only one male respondent reported injection drug use before HIV. There was a decrease in incidence of sexually transmitted infection (56.9% vs. 31.9%) after HIV diagnosis. Forty-three percent of males had traveled abroad before HIV diagnosis; among those, 30.8% reported having exchange sex while abroad. Conclusions: Our findings indicated that high-risk sexual behavior was common before HIV diagnosis and that sexual practices changed after diagnosis. Educational campaigns aimed at increasing HIV knowledge and safe sex, are critical to reduce HIV infections in Bhutan.


2019 ◽  
Author(s):  
Jenevieve Opoku ◽  
Rupali K Doshi ◽  
Amanda D Castel ◽  
Ian Sorensen ◽  
Michael Horberg ◽  
...  

BACKGROUND HIV cohort studies have been used to assess health outcomes and inform the care and treatment of people living with HIV disease. However, there may be similarities and differences between cohort participants and the general population from which they are drawn. OBJECTIVE The objective of this analysis was to compare people living with HIV who have and have not been enrolled in the DC Cohort study and assess whether participants are a representative citywide sample of people living with HIV in the District of Columbia (DC). METHODS Data from the DC Health (DCDOH) HIV surveillance system and the DC Cohort study were matched to identify people living with HIV who were DC residents and had consented for the study by the end of 2016. Analysis was performed to identify differences between DC Cohort and noncohort participants by demographics and comorbid conditions. HIV disease stage, receipt of care, and viral suppression were evaluated. Adjusted logistic regression assessed correlates of health outcomes between the two groups. RESULTS There were 12,964 known people living with HIV in DC at the end of 2016, of which 40.1% were DC Cohort participants. Compared with nonparticipants, participants were less likely to be male (68.0% vs 74.9%, <i>P</i>&lt;.001) but more likely to be black (82.3% vs 69.5%, <i>P</i>&lt;.001) and have a heterosexual contact HIV transmission risk (30.3% vs 25.9%, <i>P</i>&lt;.001). DC Cohort participants were also more likely to have ever been diagnosed with stage 3 HIV disease (59.6% vs 47.0%, <i>P</i>&lt;.001), have a CD4 &lt;200 cells/µL in 2017 (6.2% vs 4.6%, <i>P</i>&lt;.001), be retained in any HIV care in 2017 (72.9% vs 59.4%, <i>P</i>&lt;.001), and be virally suppressed in 2017. After adjusting for demographics, DC Cohort participants were significantly more likely to have received care in 2017 (adjusted odds ratio 1.8, 95% CI 1.70-2.00) and to have ever been virally suppressed (adjusted odds ratio 1.3, 95% CI 1.20-1.40). CONCLUSIONS These data have important implications when assessing the representativeness of patients enrolled in clinic-based cohorts compared with the DC-area general HIV population. As participants continue to enroll in the DC Cohort study, ongoing assessment of representativeness will be required.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristie C. Waterfield ◽  
Gulzar H. Shah ◽  
Gina D. Etheredge ◽  
Osaremhen Ikhile

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.


Author(s):  
Bernadien M. Nijmeijer ◽  
Marta Bermejo-Jambrina ◽  
Tanja M. Kaptein ◽  
Carla M. S. Ribeiro ◽  
Doris Wilflingseder ◽  
...  

AbstractSemen is important in determining HIV-1 susceptibility but it is unclear how it affects virus transmission during sexual contact. Mucosal Langerhans cells (LCs) are the first immune cells to encounter HIV-1 during sexual contact and have a barrier function as LCs are restrictive to HIV-1. As semen from people living with HIV-1 contains complement-opsonized HIV-1, we investigated the effect of complement on HIV-1 dissemination by human LCs in vitro and ex vivo. Notably, pre-treatment of HIV-1 with semen enhanced LC infection compared to untreated HIV-1 in the ex vivo explant model. Infection of LCs and transmission to target cells by opsonized HIV-1 was efficiently inhibited by blocking complement receptors CR3 and CR4. Complement opsonization of HIV-1 enhanced uptake, fusion, and integration by LCs leading to an increased transmission of HIV-1 to target cells. However, in the absence of both CR3 and CR4, C-type lectin receptor langerin was able to restrict infection of complement-opsonized HIV-1. These data suggest that complement enhances HIV-1 infection of LCs by binding CR3 and CR4, thereby bypassing langerin and changing the restrictive nature of LCs into virus-disseminating cells. Targeting complement factors might be effective in preventing HIV-1 transmission.


Author(s):  
C. P. Igweagu ◽  
O. H. Chime ◽  
C. N. Onwasigwe

HIV/AIDS continues to be a major global public health issue, having claimed more than 32 million lives so far. There were approximately 37.9 million people living with HIV/AIDS (PLHIV) at the end of 2018. Anti-retroviral therapy (ART) has significantly reduced morbidity and mortality and improved quality of life among people with HIV infection. Aims: The study was conducted to improve the knowledge and adherence to anti-retroviral therapy among PLHIV in Enugu state, southeast Nigeria. Study Design: Interventional study. Place and Duration of Study: Anti-retroviral Therapy clinics within Enugu metropolis in Enugu state Nigeria between June to December 2018. Methodology: A health education intervention was carried out among 312 PLHIV receiving ART in Enugu metropolis to improve their perception and adherence to antiretroviral therapy. A structured questionnaire was used to collect data from 312 PLHIV (156 each in the study and control groups), who were selected by multistage sampling. Subsequently, health education was conducted among the study group. Three months after this intervention its effects were assessed through a survey using the same structured questionnaires employed in the baseline survey.  Results: The most frequently occurring reason given by the respondents for poor adherence to ART was forgetfulness (65.4% for study and 69.9% for control groups). Knowledge of the factors and consequences of poor adherence to treatment was significantly higher among the study group than the controls post-interventions p<0.001. Adherence to ART improved from 42.3% pre-intervention to 81.4% post-intervention. Conclusion: Intensive health education effectively improved adherence to ART among persons living with HIV/AIDS and this should be carried out regularly.


2020 ◽  

Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. This disease is highly endemic in some regions of North America, Central America, and South America and is also reported in certain countries of Asia and Africa. It often affects people with impaired immunity, including people living with HIV, among whom the most frequent clinical presentation is disseminated histoplasmosis. The symptoms of disseminated histoplasmosis are non-specific and may be indistinguishable from those of other infectious diseases, especially disseminated tuberculosis (TB), thus complicating diagnosis and treatment. Histoplasmosis is one of the most frequent opportunistic infections caused by fungal pathogens among people living with HIV in the Americas and may be responsible for 5–15% of AIDS-related deaths every year in this Region. These guidelines aim to provide recommendations for the diagnosis, treatment, and management of disseminated histoplasmosis in persons living with HIV. Although the burden of disease is concentrated in the Americas, the recommendations presented within these guidelines are applicable globally. These guidelines were produced in accordance with the World Health Organization (WHO) handbook for guideline development. The Guideline Development Group elaborated the final recommendations based on a systematic review of scientific literature and critical evaluation of the evidence available using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. These guidelines are intended for health-care providers, HIV program managers, policy-makers, national treatment advisory boards, researchers, and other professionals involved in caring for people who either have or may be at risk of developing disseminated histoplasmosis.


2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Bahareh Torkzaban ◽  
Kalimuthusamy Natarajaseenivasan ◽  
Taha Mohseni Ahooyi ◽  
Masoud Shekarabi ◽  
Shohreh Amini ◽  
...  

Abstract HIV-1 Tat is a potent neurotoxic protein that is released by HIV-1 infected cells in the brain and perturbs neuronal homeostasis, causing a broad range of neurological disorders in people living with HIV-1. Furthermore, the effects of Tat have been addressed in numerous studies to investigate the molecular events associated with neuronal cells survival and death. Here, we discovered that exposure of rat primary neurons to Tat resulted in the up-regulation of an uncharacterized long non-coding RNA (lncRNA), LOC102549805 (lncRNA-U1). Our observations showed that increased expression of lncRNA-U1 in neurons disrupts bioenergetic pathways by dysregulating homeostasis of Ca2+, mitigating mitochondrial oxygen reduction, and decreasing ATP production, all of which point mitochondrial impairment in neurons via the Tat-mediated lncRNA-U1 induction. These changes were associated with imbalances in autophagy and apoptosis pathways. Additionally, this study showed the ability of Tat to modulate expression of the neuropeptide B/W receptor 1 (NPBWR1) gene via up-regulation of lncRNA-U1. Collectively, our results identified Tat-mediated lncRNA-U1 upregulation resulting in disruption of neuronal homeostasis.


Author(s):  
Matsobane J. Manala

The HIV/Aids pandemic is cause for great frustration to the developing countries in their attempts to improve the quality of life of their citizens. HIV/Aids in South Africa demands a specific approach to the Christian ministry in which the African world-view is acknowledged. In order for the church to play a relevant and meaningful role in combating the HIV/Aids pandemic, it is necessary that the church should be informed of the existential situation of persons living with HIV/Aids. This information is vital for raising awareness and engendering sensitivity among Christians. In the context of such awareness of and sensitivity to human pain and suffering, the community of the faithful should be moved to heed Christ’s call to show neighbourly love. The possible role of the church in caring for those who are already infected with HIV is defined.


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