scholarly journals Editing out HIV: application of gene editing technology to achieve functional cure

Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jingna Xun ◽  
Xinyu Zhang ◽  
Shuyan Guo ◽  
Hongzhou Lu ◽  
Jun Chen
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Gene Editing ◽  
Functional Cure ◽  
Hiv Replication ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Living With Hiv

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

scholarly journals Resting CD4+ T Lymphocytes but Not Thymocytes Provide a Latent Viral Reservoir in a Simian Immunodeficiency Virus-Macaca nemestrina Model of Human Immunodeficiency Virus Type 1-Infected Patients on Highly Active Antiretroviral Therapy

2003 ◽  
Vol 77 (8) ◽  
pp. 4938-4949 ◽  
Author(s):  
Anding Shen ◽  
M. Christine Zink ◽  
Joseph L. Mankowski ◽  
Karen Chadwick ◽  
Joseph B. Margolick ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Highly Active Antiretroviral Therapy ◽  
Limit Of Detection ◽  
Macaca Nemestrina ◽  
Viral Reservoir ◽  
Highly Active ◽  
Latent Viral Reservoir ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells

ABSTRACT Despite suppression of viremia in patients on highly active antiretroviral therapy (HAART), human immunodeficiency virus type 1 persists in a latent reservoir in the resting memory CD4+ T lymphocytes and possibly in other reservoirs. To better understand the mechanisms of viral persistence, we established a simian immunodeficiency virus (SIV)-macaque model to mimic the clinical situation of patients on suppressive HAART and developed assays to detect latently infected cells in the SIV-macaque system. In this model, treatment of SIV-infected pig-tailed macaques (Macaca nemestrina) with the combination of 9-R-(2-phosphonomethoxypropyl)adenine (PMPA; tenofovir) and beta-2′,3′-dideoxy-3′-thia-5-fluorocytidine (FTC) suppressed the levels of plasma virus to below the limit of detection (100 copies of viral RNA per ml). In treated animals, levels of viremia remained close to or below the limit of detection for up to 6 months except for an isolated “blip” of detectable viremia in each animal. Latent virus was measured in blood, spleen, lymph nodes, and thymus by several different methods. Replication-competent virus was recovered after activation of a 99.5% pure population of resting CD4+ T lymphocytes from a lymph node of a treated animal. Integrated SIV DNA was detected in resting CD4+ T cells from spleen, peripheral blood, and various lymph nodes including those draining the gut, the head, and the limbs. In contrast to the wide distribution of latently infected cells in peripheral lymphoid tissues, neither replication-competent virus nor integrated SIV DNA was detected in thymocytes, suggesting that thymocytes are not a major reservoir for virus in pig-tailed macaques. The results provide the first evidence for a latent viral reservoir for SIV in macaques and the most extensive survey of the distribution of latently infected cells in the host.

scholarly journals Effect of Latent Human Immunodeficiency Virus Infection on Cell Surface Phenotype

2002 ◽  
Vol 76 (4) ◽  
pp. 1673-1681 ◽  
Author(s):  
David G. Brooks ◽  
Jerome A. Zack
Keyword(s):  
Human Immunodeficiency Virus ◽  
Highly Active Antiretroviral Therapy ◽  
Virus Production ◽  
Cellular Interactions ◽  
Cellular Activation ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells

ABSTRACT Highly active antiretroviral therapy has succeeded in many cases in suppressing virus production in patients infected with human immunodeficiency virus (HIV); however, once treatment is discontinued, virus replication is rekindled. One reservoir capable of harboring HIV in a latent state and igniting renewed infection once therapy is terminated is a resting T cell. Due to the sparsity of T cells latently infected with HIV in vivo, it has been difficult to study viral and cellular interactions during latency. The SCID-hu (Thy/Liv) mouse model of HIV latency, however, provides high percentages of latently infected cells, allowing a detailed analysis of phenotype. Herein we show that latently infected cells appear phenotypically normal. Following cellular stimulation, the virus completes its life cycle and induces phenotypic changes, such as CD4 and major histocompatibility complex class I down-regulation, in the infected cell. In addition, HIV expression following activation did not correlate with expression of the cellular activation marker CD25. The apparently normal phenotype and lack of HIV expression in latently infected cells could prevent recognition by the immune response and contribute to the long-lived nature of this reservoir.

Therapeutic strategies to fight HIV-1 latency: progress and challenges

Biologia ◽  
2017 ◽  
Vol 72 (10) ◽  
Author(s):  
Sello Lebohang Manoto ◽  
Lebogang Thobakgale ◽  
Rudzani Malabi ◽  
Charles Maphanga ◽  
Saturnin Ombinda-Lemboumba ◽  
...  
Keyword(s):  
Immune System ◽  
Highly Active Antiretroviral Therapy ◽  
Laser Pulses ◽  
Femtosecond Laser Pulses ◽  
Host Immune System ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

AbstractThe life-long persistence of human immunodeficiency virus type-1 (HIV-1) in latent reservoirs is a major hurdle in the eradication of HIV-1, even though highly active antiretroviral therapy (HAART) can be effective in reducing the plasma HIV-1 RNA to less than 50 copies per mL, which is below the detection limit of most clinical assays. In the latent reservoirs the provirus is integrated in the host genome but does not actively replicate and thus is not inhibited by HAART or recognized by the host immune system. There has been increasing scientific interest and investment into research towards HIV cure due to the challenges and limitation of life long treatment. The various strategies that have been developed aim to activate gene expression in HIV latent cells which might lead to the elimination of the virus by HAART or the immune system. In this review we discuss latency and therapeutic approaches that are being evaluated to eradicate HIV latently infected cells to overcome the burden of life long HAART. In addition, we explore the possibility of delivering HAART in latently infected cells using femtosecond laser pulses, a topic closely studied in our research.

scholarly journals Induction of Autophagy to Achieve a Human Immunodeficiency Virus Type 1 Cure

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1798
Author(s):  
Grant R. Campbell ◽  
Stephen A. Spector
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Functional Cure ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Infected Cells ◽  
Hiv 1

Effective antiretroviral therapy has led to significant human immunodeficiency virus type 1 (HIV-1) suppression and improvement in immune function. However, the persistence of integrated proviral DNA in latently infected reservoir cells, which drive viral rebound post-interruption of antiretroviral therapy, remains the major roadblock to a cure. Therefore, the targeted elimination or permanent silencing of this latently infected reservoir is a major focus of HIV-1 research. The most studied approach in the development of a cure is the activation of HIV-1 expression to expose latently infected cells for immune clearance while inducing HIV-1 cytotoxicity—the “kick and kill” approach. However, the complex and highly heterogeneous nature of the latent reservoir, combined with the failure of clinical trials to reduce the reservoir size casts doubt on the feasibility of this approach. This concern that total elimination of HIV-1 from the body may not be possible has led to increased emphasis on a “functional cure” where the virus remains but is unable to reactivate which presents the challenge of permanently silencing transcription of HIV-1 for prolonged drug-free remission—a “block and lock” approach. In this review, we discuss the interaction of HIV-1 and autophagy, and the exploitation of autophagy to kill selectively HIV-1 latently infected cells as part of a cure strategy. The cure strategy proposed has the advantage of significantly decreasing the size of the HIV-1 reservoir that can contribute to a functional cure and when optimised has the potential to eradicate completely HIV-1.

scholarly journals Chronic Cystoisospora belli infection in a Colombian patient living with HIV and poor adherence to highly active antiretroviral therapy

Biomédica ◽  
2021 ◽  
Vol 41 (Supl. 1) ◽  
pp. 17-22
Author(s):  
Ana Luz Galván-Díaz ◽  
Juan Carlos Alzate ◽  
Esteban Villegas ◽  
Sofía Giraldo ◽  
Jorge Botero ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Diarrheal Disease ◽  
Opportunistic Infections ◽  
Poor Adherence ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Living With Hiv

Cystoisospora belli is an intestinal Apicomplexan parasite associated with diarrheal illness and disseminated infections in humans, mainly immunocompromised individuals such as those living with the human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). An irregular administration of highly active antiretroviral therapy (HAART) in HIV patients may increase the risk of opportunistic infections like cystoisosporiasis.We describe here a case of C. belli infection in a Colombian HIV patient with chronic gastrointestinal syndrome and poor adherence to HAART. His clinical and parasitological cure was achieved with trimethoprim-sulfamethoxazole treatment. Although a reduction in the number of C. belli cases has been observed since the use of HAART, this parasite still has to be considered as a differential diagnosis of diarrheal disease in HIV/AIDS patients.Effective interventions enhancing adherence to HAART should be included in HIV patient care programs.

scholarly journals Prevention, Rehabilitation, and Mitigation Strategies of Cognitive Deficits in Aging with HIV: Implications for Practice and Research

ISRN Nursing ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-21 ◽  
Author(s):  
David E. Vance
Keyword(s):  
Cognitive Deficits ◽  
Highly Active Antiretroviral Therapy ◽  
Successful Aging ◽  
Mitigation Strategies ◽  
Medical Decision ◽  
Everyday Functioning ◽  
Highly Active ◽  
Living With Hiv ◽  
Speed Of Processing Training

Highly active antiretroviral therapy has given the chance to those living with HIV to keep on living, allowing them the opportunity to age and perhaps age successfully. Yet, there are severe challenges to successful aging with HIV, one of which is cognitive deficits. Nearly half of those with HIV experience cognitive deficits that can interfere with everyday functioning, medical decision making, and quality of life. Given that cognitive deficits develop with more frequency and intensity with increasing age, concerns mount that as people age with HIV, they may experience more severe cognitive deficits. These concerns become especially germane given that by 2015, 50% of those with HIV will be 50 and older, and this older cohort of adults is expected to grow. As such, this paper focuses on the etiologies of such cognitive deficits within the context of cognitive reserve and neuroplasticity. From this, evidence-based and hypothetical prevention (i.e., cognitive prescriptions), rehabilitation (i.e., speed of processing training), and mitigation (i.e., spaced retrieval method) strategies are reviewed. Implications for nursing practice and research are posited.

scholarly journals Assessment of ART knowledge and adherence to ARVs among PLWHA accessing care in two Nigerian Military HIV/AIDS Treatment sites

2018 ◽  
Vol 4 (1) ◽  
pp. 43-52
Author(s):  
David Ufuoma Adje ◽  
Felicia Esemekiphorar Williams ◽  
Chukwuka Nicholas Bezugbe ◽  
Dauda Audi Dangiwa
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
People Living With Hiv ◽  
Systematic Random Sampling ◽  
Highly Active ◽  
Study Sites ◽  
Living With Hiv ◽  
Busy Schedule ◽  
Hiv Aids

Background:       Adherence to Highly Active Antiretroviral Therapy (HAART) is critical in achieving treatment goals, avoiding antimicrobial resistance, preventing treatment failure and improving the patient’s quality of life. Objectives: To assess the knowledge of antiretroviral therapy (ART) and adherence to antiretroviral (ARVs) medicines amongst People Living With HIV/AIDS (PLWHA) accessing care in two Nigerian Military HIV/AIDS Treatment sites. Methods: Four hundred patients on HAART who visited the study sites during the study period were recruited for the study using systematic random sampling method. A semi-structured, pretested, interviewer-administered questionnaire was used to obtain demographic details. Patients’ knowledge of HIV was assessed using an 8-item questionnaire while adherence was measured using the Simplified Medication Adherence Questionnaire (SMAQ). Results: The predominant age group was 31-40 years (46.4%). There were more females (69%) than males (31%). Only 45.5% answered knowledge questions correctly. The adherence level in this study was 64.0%. The major reasons cited for non-adherence included being away from home (23.6%), forgetfulness (17.1%), busy schedule (14%), need to conceal medication (12.7%) and feeling better (11.6%). Conclusion: Patients’ knowledge of ART and adherence to ARVs medicines were sub-optimal. Appropriate strategies to improve patients’ knowledge of ART and adherence to ARVs are recommended.

scholarly journals Chronic Pain in HIV

2020 ◽  
Vol 16 ◽  
pp. 174480692092727 ◽  
Author(s):  
Dylan R Addis ◽  
Jennifer J DeBerry ◽  
Saurabh Aggarwal
Keyword(s):  
Chronic Pain ◽  
Peripheral Neuropathy ◽  
Highly Active Antiretroviral Therapy ◽  
Chronic Widespread Pain ◽  
High Rate ◽  
Widespread Pain ◽  
Drug Induced ◽  
Highly Active ◽  
Immunodeficiency Virus

The evolution of therapeutics for and management of human immunodeficiency virus-1 (HIV-1) infection has shifted it from predominately manifesting as a severe, acute disease with high mortality to a chronic, controlled infection with a near typical life expectancy. However, despite extensive use of highly active antiretroviral therapy, the prevalence of chronic widespread pain in people with HIV remains high even in those with a low viral load and high CD4 count. Chronic widespread pain is a common comorbidity of HIV infection and is associated with decreased quality of life and a high rate of disability. Chronic pain in people with HIV is multifactorial and influenced by HIV-induced peripheral neuropathy, drug-induced peripheral neuropathy, and chronic inflammation. The specific mechanisms underlying these three broad categories that contribute to chronic widespread pain are not well understood, hindering the development and application of pharmacological and nonpharmacological approaches to mitigate chronic widespread pain. The consequent insufficiencies in clinical approaches to alleviation of chronic pain in people with HIV contribute to an overreliance on opioids and alarming rise in active addiction and overdose. This article reviews the current understanding of the pathogenesis of chronic widespread pain in people with HIV and identifies potential biomarkers and therapeutic targets to mitigate it.

scholarly journals Liver disease, HIV and aging

Sexual Health ◽  
2011 ◽  
Vol 8 (4) ◽  
pp. 512 ◽  
Author(s):  
Oluwaseun Falade-Nwulia ◽  
Chloe L. Thio
Keyword(s):  
Liver Disease ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Future Research ◽  
Hiv Replication ◽  
Highly Active ◽  
Living With Hiv ◽  
The Impact ◽  
Hiv Negative

The life expectancy of HIV-infected patients has increased due to the efficacy of highly active antiretroviral therapy (HAART) in controlling HIV replication; thus, the population living with HIV infection is steadily aging. Liver-related morbidity and mortality has emerged as a leading problem in HIV-infected patients. Since aging, HIV infection and HAART all affect the liver, understanding the impact of the combination of these factors on liver disease is crucial for optimisation of care in the aging HIV-infected population. This review will focus on the current understanding of liver disease in older (>50 years old) HIV-negative individuals and in HIV-infected individuals. Areas for future research in the area of HIV, liver disease and aging will also be discussed.

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