functional cure
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Retrovirology ◽  
2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Samira Joussef-Piña ◽  
Immaculate Nankya ◽  
Sophie Nalukwago ◽  
Joy Baseke ◽  
Sandra Rwambuya ◽  
...  

Abstract Background Our understanding of the peripheral human immunodeficiency virus type 1 (HIV-1) reservoir is strongly biased towards subtype B HIV-1 strains, with only limited information available from patients infected with non-B HIV-1 subtypes, which are the predominant viruses seen in low- and middle-income countries (LMIC) in Africa and Asia. Results In this study, blood samples were obtained from well-suppressed ART-experienced HIV-1 patients monitored in Uganda (n = 62) or the U.S. (n = 50), with plasma HIV-1 loads < 50 copies/ml and CD4+ T-cell counts > 300 cells/ml. The peripheral HIV-1 reservoir, i.e., cell-associated HIV-1 RNA and proviral DNA, was characterized using our novel deep sequencing-based EDITS assay. Ugandan patients were slightly younger (median age 43 vs 49 years) and had slightly lower CD4+ counts (508 vs 772 cells/ml) than U.S. individuals. All Ugandan patients were infected with non-B HIV-1 subtypes (31% A1, 64% D, or 5% C), while all U.S. individuals were infected with subtype B viruses. Unexpectedly, we observed a significantly larger peripheral inducible HIV-1 reservoir in U.S. patients compared to Ugandan individuals (48 vs. 11 cell equivalents/million cells, p < 0.0001). This divergence in reservoir size was verified measuring proviral DNA (206 vs. 88 cell equivalents/million cells, p < 0.0001). However, the peripheral HIV-1 reservoir was more diverse in Ugandan than in U.S. individuals (8.6 vs. 4.7 p-distance, p < 0.0001). Conclusions The smaller, but more diverse, peripheral HIV-1 reservoir in Ugandan patients might be associated with viral (e.g., non-B subtype with higher cytopathicity) and/or host (e.g., higher incidence of co-infections or co-morbidities leading to less clonal expansion) factors. This highlights the need to understand reservoir dynamics in diverse populations as part of ongoing efforts to find a functional cure for HIV-1 infection in LMICs.


2022 ◽  
Vol 000 (000) ◽  
pp. 000-000
Author(s):  
Jing Pan ◽  
Haiyan Wang ◽  
Tiantian Yao ◽  
Xuejiao Liao ◽  
Hao Cheng ◽  
...  

2021 ◽  
Author(s):  
Hannah S.J. Choi ◽  
Alexander Tonthat ◽  
Harry L.A. Janssen ◽  
Norah A. Terrault

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 113-121
Author(s):  
Michael J. Mauro

Abstract Beginning with imatinib and now spanning 6 oral, highly active, and mostly safe agents, the development of specific targeted therapy for patients with chronic myeloid leukemia (CML) has created a new world featuring chronic maintenance chemotherapy for all treated as such, treatment-free remission, and functional cure after prolonged deep remission in a subset. As a result comes a necessary shift in focus from acute to chronic toxicity, increasing attention to patient comorbidities, and critical thinking around specific adverse events such as metabolic, cardiovascular, and cardiopulmonary effects, which vary from agent to agent. This review aims to pull together the state of the art of managing the “C” in CML—a chronic myeloproliferative neoplasm treated at present over many years with oral BCR-ABL-targeted agents in a population whose overall health can be complex and potentially affected by disease and therapy—and determine how we can better manage a highly treatable and increasingly curable cancer.


Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jingna Xun ◽  
Xinyu Zhang ◽  
Shuyan Guo ◽  
Hongzhou Lu ◽  
Jun Chen

AbstractHighly active antiretroviral therapy (HAART) successfully suppresses human immunodeficiency virus (HIV) replication and improves the quality of life of patients living with HIV. However, current HAART does not eradicate HIV infection because an HIV reservoir is established in latently infected cells and is not recognized by the immune system. The successful curative treatment of the Berlin and London patients following bone marrow transplantation inspired researchers to identify an approach for the functional cure of HIV. As a promising technology, gene editing-based strategies have attracted considerable attention and sparked much debate. Herein, we discuss the development of different gene editing strategies in the functional cure of HIV and highlight the potential for clinical applications prospects. Graphical Abstract


Gut ◽  
2021 ◽  
pp. gutjnl-2021-326258
Author(s):  
Antonio Bertoletti ◽  
Carolina Boni
Keyword(s):  

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaofan Yang ◽  
Ting Huang ◽  
Tiantian Wang ◽  
Hongbo Gao ◽  
Haitao Zhang ◽  
...  

Antiretroviral drugs effectively halt HIV-1 replication and disease progression, however, due to the presence of a stable viral latent reservoir, the infection cannot be cured by antiretroviral drugs alone. Elucidating the molecular mechanisms underlying HIV-1 latent infection remains a critical hurdle that precludes the development of novel therapeutic strategies aiming for a potential functional cure. Cellular metabolism has been reported to affect HIV-1 replication in CD4+ T cells, but it remains largely unclear whether it is involved in the regulation of HIV-1 latency. Here, we performed a sub-pooled CRISPR library knockout screen targeting 1773 metabolic-related genes in a cell model of HIV-1 latent infection and found that Methionine Adenosyltransferase 2A (MAT2A) contributes to HIV-1 latency. MAT2A knockout enhanced the reactivation of latent HIV-1 while MAT2A overexpression did the opposite. Mechanistically, MAT2A modulates HIV-1 latency through S-Adenosylmethionine (SAM)-mediated one-carbon flux. MAT2A knockout resulted in a significant downregulation of DNA and histone methylation at the HIV-1 5’-LTR. Importantly, we found that the plasma level of SAM is positively correlated with HIV-1 DNA in PBMCs from ART-treated infected individuals, suggesting SAM could serve as a potential biomarker for the latent viral reservoir. Overall, this study reveals an important role of MAT2A-mediated one-carbon metabolism in regulating HIV-1 latency and provides a promising target for the development of new strategies for a functional cure of HIV-1.


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