scholarly journals Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Flora Mikaeloff ◽  
Sara Svensson Akusjärvi ◽  
George Mondinde Ikomey ◽  
Shuba Krishnan ◽  
Maike Sperk ◽  
...  

AbstractDespite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5 years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon, and India, respectively, to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported. A significantly lower level of neurosteroids was observed in both cohorts and could potentiate neurological impairments in PLWH. Further, modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells.

2021 ◽  
Author(s):  
Flora Mikaeloff ◽  
Sara Svensson-Akusjarvi ◽  
George Mondinde Ikomey ◽  
Shuba Krishnan ◽  
Maike Sperk ◽  
...  

Despite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic adaptation in people living with HIV (PLWH). The successful short-term cART reported abnormalities in the metabolic reprogramming in PLWH, but the long-term consequences are unknown. This study investigated alterations in the plasma metabolic profiles by comparing PLWH and matched HIV-negative controls (HC) from Cameroon and India. We used untargeted and targeted LC-MS/MS-based metabolic profiling in PLWH with long-term (>5years) successful therapy in a trans cohorts approach. Advanced statistical and bioinformatics analyses showed altered amino acid metabolism, more specifically to glutaminolysis in PLWH with therapy than HIV-negative controls that can lead to excitotoxicity in both the cohorts. A significantly lower level of neurosteroids was observed in both cohorts and could potentiate neurological impairments in PLWH. The modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells. Our patient-based metabolomics and in vitro study, therefore, highlight the importance of altered glutaminolysis in PLWH that can be linked accelerated neurocognitive aging and metabolic reprogramming in latently infected cells.


2020 ◽  
Vol 12 (1) ◽  
pp. 65-72
Author(s):  
N. G. Doronin ◽  
S. N. Khoroshkov ◽  
S. L. Maksimov

Objective. Develop an algorithm for determining tactics and parameters of their treatment to improve treatment outcomes. Methodology. Material and research methods. A statistical analysis of the treatment results of 90 HIV-infected patients aged from 23 to 54 years with extra-articular fractures of long bones of the extremities was carried out. When determining the tactics and method of treatment, the peculiarities of the effect of HIV infection, antiretroviral drugs, and opportunistic diseases on the patient’s body were not taken into account. Results. Non-infectious complications are characteristic of HIV-infected patients: sides of the postoperative wound (seromas, hematomas, discrepancy of wound edges, delayed crushing), aseptic loosening and migration of fixatives, delayed consolidation of fractures. The presence of a statistically significant relationship between the objective factors characterizing the course of HIV infection: the stage of the disease, the number of CD lymphocytes, the ratio of CD4 / CD8 lymphocytes, viral load and the risk of postoperative complications was revealed.Conclusion. The application of the developed algorithm allows you to objectify the procedure and provide an individual approach in determining the tactics and method of treatment for HIV-infected patients with extraarticular fractures of long bones of the extremities


2021 ◽  
Author(s):  
Sofie Olund Villumsen ◽  
Rui Benfeitas ◽  
Andreas D Knudsen ◽  
Marco Gelpi ◽  
Julie Hogh ◽  
...  

People living with HIV (PLWH) require life-long anti-retroviral treatment and often present with comorbidities such as metabolic syndrome (MetS). A systematic lipidomic characterization and its association with metabolism is currently missing. In this study, we included 100 PLWH with MetS and 100 without MetS from the Copenhagen comorbidity in HIV infection (COCOMO) cohort to examine whether and how lipidome profiles associated with MetS in PLWH. We combined several standard biostatistical, machine learning, and network analysis techniques to investigate the lipidome systematically and comprehensively. Our observations indicate an increased abundance of the glycerolipids and an association between structural composition patterns of glycerolipids in PLWH with MetS. Further integration of the key metabolites identified earlier in the same population and clinical data with lipidomics suggest disruption of the glutamate and fatty acid metabolism. suggest their involvement in pathogenesis of PLWH with MetS.


Author(s):  
Alan Whiteside

The response to HIV and AIDS has to be funded, whether the emphasis is on prevention, treatment, or both. AIDS is unique in part because of its complex financing. It requires long-term commitments for those increasing numbers on relatively expensive lifesaving treatment. ‘Funding the epidemic’ looks at the history of funding from the mobilization of international money into low- to middle-income countries to the increased domestic funding from government budgets fed from general tax revenues. Looking forward, AIDS resource needs are projected to increase at least until 2020. The problem is that treatment for people living with HIV is long-term and these costs remain unacknowledged by governments and donors.


Angiology ◽  
2018 ◽  
Vol 70 (5) ◽  
pp. 448-457 ◽  
Author(s):  
Mina Psichogiou ◽  
Chris J. Kapelios ◽  
Giorgos Konstantonis ◽  
Antonis Argyris ◽  
Euthimia Nasothimiou ◽  
...  

Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals, respectively, at baseline. HIV infection was independently associated with carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was independently associated with age, years of smoking, and exposure to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5 cases/100 patients, respectively. Carotid atheromatosis progression was significantly associated with NNRTI exposure. People living with HIV infection exhibited high prevalence and incidence of subclinical arterial damage and site-specific predilection for the carotids. These investigations may help optimize HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis, emphasizing the need to consider the atherogenic potential of antiretroviral drugs in management strategies.


Author(s):  
Ridwan Balatif

Acquired Immunodeficiency Syndrome (AIDS) was first known in 1981 in homosexual groups who had opportunistic infections and malignancies. In Indonesia the first AIDS case was reported in 1987 to a Dutch citizen living in the province of Bali. Cases of HIV infection in Indonesia are reported to increase every year and most occur at the age of 25-49 years. HIV transmission is not easily transmitted, even when an HIV-infected person takes antiretroviral drugs can reduce the risk of transmission by up to 96%. But one of the biggest challenges in managing HIV infection is facing stigma and discrimination. As many as 1 in 5 people living with HIV are afraid to come to the clinic because they will experience discrimination and stigma from the community if this condition occurs will cause treatment delay until PLWHA (People living with HIV/AIDS) will fall to the AIDS stage and PLWHA will be susceptible to opportunistic infections. A clinic in Namibia, when stigma and discrimination were successfully overcome, there was a 20% reduction in mortality in PLWHA


2021 ◽  
Vol 12 ◽  
Author(s):  
Lam Ngoc Thao Nguyen ◽  
Lam Nhat Nguyen ◽  
Juan Zhao ◽  
Madison Schank ◽  
Xindi Dang ◽  
...  

T cells are critical for the control of viral infections and T cell responses are regulated by a dynamic network of non-coding RNAs, including microRNAs (miR) and long non-coding RNAs (lncRNA). Here we show that an activation-induced decline of lncRNA growth arrest-specific transcript 5 (GAS5) activates DNA damage response (DDR), and regulates cellular functions and apoptosis in CD4 T cells derived from people living with HIV (PLHIV) via upregulation of miR-21. Notably, GAS5-miR21-mediated DDR and T cell dysfunction are observed in PLHIV on antiretroviral therapy (ART), who often exhibit immune activation due to low-grade inflammation despite robust virologic control. We found that GAS5 negatively regulates miR-21 expression, which in turn controls critical signaling pathways involved in DNA damage and cellular response. The sustained stimulation of T cells decreased GAS5, increased miR-21 and, as a result, caused dysfunction and apoptosis in CD4 T cells. Importantly, this inflammation-driven T cell over-activation and aberrant apoptosis in ART-controlled PLHIV and healthy subjects (HS) could be reversed by antagonizing the GAS5-miR-21 axis. Also, mutation of the miR-21 binding site on exon 4 of GAS5 gene to generate a GAS5 mutant abolished its ability to regulate miR-21 expression as well as T cell activation and apoptosis markers compared to the wild-type GAS5 transcript. Our data suggest that GAS5 regulates TCR-mediated activation and apoptosis in CD4 T cells during HIV infection through miR-21-mediated signaling. However, GAS5 effects on T cell exhaustion during HIV infection may be mediated by a mechanism beyond the GAS5-miR-21-mediated signaling. These results indicate that targeting the GAS5-miR-21 axis may improve activity and longevity of CD4 T cells in ART-treated PLHIV. This approach may also be useful for targeting other infectious or inflammatory diseases associated with T cell over-activation, exhaustion, and premature immune aging.


2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Tri Nurhudi Sasono

Abstract : Indicator of the health welfare through Sustanable Development Goals (SDGs) is to reduce the incidence of HIV-AIDS, decrease the rate of the epidemic and maintain the quality of life of people living with HIV-AIDS (PLWHA). Trend cases of HIV-AIDS is the most recent spread among people, especially housewives. In Malang until 2015 found 278 Housewife of 409 cases of AIDS. The prevalence of HIV-AIDS in Malang Regency is ranked second after Surabaya city in East Java. For the importance of public participation and citizen care AIDS Cahaya Care Turen take responsibility for the condition. Determination Rule Goverment number 2 2015 year on the Participation of the community response to HIV-AIDS in Malang as a legal rule. Concerned Citizens activities AIDS (WPA). WPA Cahaya Care Turen is increases HIV risk and quality of life PLWHA. The purpose of this study was to determine the role of Citizens AIDS Cahaya Care Quality of Care Turen against people living with HIV in Puskesmas Turen Malang. The study design using a quasi-experimental, with purposive sampling using a sampling technique. Total number of research subjects 23. Based on test results obtained with the Wilcoxon p value <0.005, which means that there is a significant difference before and after PLWHA joining participated in the WPA Cahaya Care Turen. The conclusion of this study is WPA activities involving people living with HIV and at risk groups can optimize compliance with antiretroviral drugs that have an impact on improving the quality of life of PLHIV. Suggestions in this research is done WPA Program activities are structured and ongoing cross-sector in order to improve the quality of life and empower PLWHA.Keywords : WPA Cahaya Care Turen, Quality of life, PLWHA Abstrak : Salah satu indikator kesejahteraan kesehatan melalui Sustanable Development Goals (SDGs) adalah menekan angka kejadian HIV-AIDS, menurunkan laju epidemik dan mempertahankan kualitas hidup Orang dengan HIV-AIDS (ODHA). Trend kasus HIV-AIDS terkini terbanyak adalah menjangkit dikalangan masyarakat khususnya pada ibu rumah tangga. Kabupaten Malang sampai dengan tahun 2015 ditemukan 278 Ibu Rumah Tangga dari 409 kasus AIDS. Prevalensi HIV-AIDS di Kabupaten Malang ini merupakan peringkat kedua di Jawa Timur setelah Kota Surabaya. Untuk itu pentingnya peran serta masyarakat dan warga peduli AIDS Cahaya Care Turen ikut bertanggung jawab terhadap kondisi tersebut. Penetapan Peraturan Bupati Malang no.2 th.2015 tentang Peran serta masyarakat penanggulangan HIV-AIDS di Kabupaten Malang diharapkan dapat mengurangi risiko penularan HIV dan meningkatkan kualitas hidup ODHA. Tujuan dari penelitian ini adalah untuk mengetahui Peran Warga Peduli AIDS Cahaya Care Turen terhadap Kualitas ODHA Di Wilayah Kerja Puskesmas Turen Kabupaten Malang. Desain penelitian menggunakan quasi eksperimen, dengan teknik sampling menggunakan purposive sampling. Jumlah subyek penelitian sejumlah 23. Berdasarkan hasil uji dengan Wilcoxon didapatkan nilai p value < 0.005 yang berarti bahwa terdapat perbedaan bermakna sebelum dan sesudah ODHA bergabung mengikuti kegiatan WPA Cahaya Care Turen. Kesimpulan dalam penelitian ini adalah kegiatan WPA dengan melibatkan ODHA dan kelompok beresiko dapat mengoptimalkan kepatuhan obat ART sehingga berdampak terhadap peningkatan kualitas hidup ODHA. Saran dalam penelitian ini adalah dilakukannya Program kegiatan WPA yang terstruktur dan berkesinambungan lintas sektor guna meningkatkan kualitas hidup dan memberdayakan ODHA.     Kata kunci : WPA Cahaya Care Turen, kualitas hidup, ODHA


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 909
Author(s):  
Laura Cheney ◽  
John M. Barbaro ◽  
Joan W. Berman

Antiretroviral drugs have dramatically improved the morbidity and mortality of people living with HIV (PLWH). While current antiretroviral therapy (ART) regimens are generally well-tolerated, risks for side effects and toxicity remain as PLWH must take life-long medications. Antiretroviral drugs impact autophagy, an intracellular proteolytic process that eliminates debris and foreign material, provides nutrients for metabolism, and performs quality control to maintain cell homeostasis. Toxicity and adverse events associated with antiretrovirals may be due, in part, to their impacts on autophagy. A more complete understanding of the effects on autophagy is essential for developing antiretroviral drugs with decreased off target effects, meaning those unrelated to viral suppression, to minimize toxicity for PLWH. This review summarizes the findings and highlights the gaps in our knowledge of the impacts of antiretroviral drugs on autophagy.


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