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Emerging Infectious Diseases Jun 2021June 2021 marks the 40th anniversary of the first description of AIDS. On the 30th anniversary, we defined priorities as improving use of existing interventions,... (Review)
Review
June 2021 marks the 40th anniversary of the first description of AIDS. On the 30th anniversary, we defined priorities as improving use of existing interventions, clarifying optimal use of HIV testing and antiretroviral therapy for prevention and treatment, continuing research, and ensuring sustainability of the response. Despite scientific and programmatic progress, the end of AIDS is not in sight. Other major epidemics over the past decade have included Ebola, arbovirus infections, and coronavirus disease (COVID-19). A benchmark against which to compare other global interventions is the HIV/AIDS response in terms of funding, coordination, and solidarity. Lessons from Ebola and HIV/AIDS are pertinent to the COVID-19 response. The fifth decade of AIDS will have to position HIV/AIDS in the context of enhanced preparedness and capacity to respond to other potential pandemics and transnational health threats.
Topics: Acquired Immunodeficiency Syndrome; COVID-19; HIV Infections; Hemorrhagic Fever, Ebola; Humans; Pandemics; SARS-CoV-2
PubMed: 34013858
DOI: 10.3201/eid2706.210284 -
International Journal of Molecular... Jan 2023Human immunodeficiency virus (HIV) infections and HIV-induced acquired immunodeficiency syndrome (AIDS) continue to represent a global health burden. There is currently... (Review)
Review
Human immunodeficiency virus (HIV) infections and HIV-induced acquired immunodeficiency syndrome (AIDS) continue to represent a global health burden. There is currently no effective vaccine, nor any cure, for HIV infections; existing antiretroviral therapy can suppress viral replication, but only as long as antiviral drugs are taken. HIV infects cells of the host immune system, and it can establish a long-lived viral reservoir, which can be targeted and edited through gene therapy. Gene editing platforms based on the clustered regularly interspaced palindromic repeat-Cas system (CRISPR-Cas) have been recognized as promising tools in the development of gene therapies for HIV infections. In this review, we evaluate the current landscape of CRISPR-Cas-based therapies against HIV, with an emphasis on the infection biology of the virus as well as the activity of host restriction factors. We discuss the potential of a combined CRISPR-Cas approach that targets host and viral genes to activate antiviral host factors and inhibit viral replication simultaneously. Lastly, we focus on the challenges and potential solutions of CRISPR-Cas gene editing approaches in achieving an HIV cure.
Topics: Humans; Acquired Immunodeficiency Syndrome; CRISPR-Cas Systems; HIV Infections; Gene Editing; Viruses; Antiviral Agents
PubMed: 36675077
DOI: 10.3390/ijms24021563 -
Journal of Leukocyte Biology Apr 2020The morbidity and mortality of HIV type-1 (HIV-1)-related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy,... (Review)
Review
The morbidity and mortality of HIV type-1 (HIV-1)-related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV-1 replication and gradual recovery of CD4 T-cell counts. However, ∼10-40% of HIV-1-infected individuals fail to achieve normalization of CD4 T-cell counts despite persistent virological suppression. These patients are referred to as "inadequate immunological responders," "immunodiscordant responders," or "immunological non-responders (INRs)" who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non-AIDS events and present higher rates of mortality than HIV-1-infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV-1-infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.
Topics: Acquired Immunodeficiency Syndrome; Antiretroviral Therapy, Highly Active; Gastrointestinal Microbiome; Humans; Immune Reconstitution
PubMed: 31965635
DOI: 10.1002/JLB.4MR1019-189R -
Cell Oct 2020The human immunodeficiency virus, the lentivirus that causes AIDS, is responsible for the most prevalent epidemic in the history of mankind. Here in this Timeline, we...
The human immunodeficiency virus, the lentivirus that causes AIDS, is responsible for the most prevalent epidemic in the history of mankind. Here in this Timeline, we have attempted to illustrate a short history of HIV-1, from its identification in landmark papers published by Robert Gallo, Myron Essex, and Luc Montagnier, to the numerous drug and vaccine trials as well as the stride toward a possible cure. Even today, a vaccine and cure against HIV-1 remains elusive. In spite of this, in the space of 30 years, from the time when being HIV positive meant an instant death sentence, to today where millions of HIV positive people are living normal lives, the progress we have made in such a short period of time should be celebrated. To view this Timeline, open or download the PDF.
Topics: Acquired Immunodeficiency Syndrome; HIV Infections; HIV-1; History, 20th Century; History, 21st Century; Humans
PubMed: 33064990
DOI: 10.1016/j.cell.2020.09.004 -
Virologica Sinica Feb 2022Although tremendous efforts have been made to prevent and treat HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. The combination antiretroviral... (Review)
Review
Although tremendous efforts have been made to prevent and treat HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. The combination antiretroviral therapy (cART), although able to suppress HIV-1 replication, cannot eliminate the proviral DNA integrated into the human genome and thus requires lifelong treatment that may lead to various side effects. In recent years, clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) related gene-editing systems have been developed and designed as effective ways to treat HIV-1 infection. However, new gene-targeting tools derived from or functioning like CRISPR/Cas9, including base editor, prime editing, SHERLOCK, DETECTR, PAC-MAN, ABACAS, pfAGO, have been developed and optimized for pathogens detection and diseases correction. Here, we summarize recent studies on HIV-1/AIDS gene therapy and provide more gene-editing targets based on studies relating to the molecular mechanism of HIV-1 infection. We also identify the strategies and potential applications of these new gene-editing technologies for HIV-1/AIDS treatment in the future. Moreover, we discuss the caveats and problems that should be addressed before the clinical use of these versatile CRISPR-based gene targeting tools. Finally, we offer alternative solutions to improve the practice of gene targeting in HIV-1/AIDS gene therapy.
Topics: Acquired Immunodeficiency Syndrome; CRISPR-Cas Systems; Gene Editing; Genetic Therapy; Genome, Human; HIV-1; Humans
PubMed: 35234622
DOI: 10.1016/j.virs.2022.01.017 -
Current HIV/AIDS Reports Feb 2020The introduction of the National Free Antiretroviral Therapy Program (NFATP) in 2003 by the China National Center for AIDS/STD Control and Prevention has led to dramatic... (Review)
Review
PURPOSE OF REVIEW
The introduction of the National Free Antiretroviral Therapy Program (NFATP) in 2003 by the China National Center for AIDS/STD Control and Prevention has led to dramatic increases in antiretroviral therapy (ART) coverage among HIV-infected Chinese patients. Despite limitations in the number of available free antiretroviral drugs, the overall mortality associated with HIV/AIDS has dropped from 39.3 per 100 person-years in 2002 to 3.1 in 2014. In this review, we summarize the challenges, responses, and achievements of antiretroviral therapy (ART) in China over the past 20 years.
RECENT FINDINGS
Continuous optimization of the Chinese National Guidelines for HIV/AIDS Diagnosis and Treatment has been guided by data from serial domestic multi-center studies aimed at evaluating efficacy and toxicity of available ART regimens among Chinese patients with HIV, with the goal of maximizing adherence, access, and efficacy. In addition, increasing attention has been focused on the importance of continuity in the HIV care cascade to promote linkage to care, and address the multidisciplinary chronic care needs HIV/AIDS patients on lifelong ART. Great progress has been achieved in the past 20 years in terms of access to and optimization of antiretroviral treatment in China. As the number of patients receiving long-term ART continues to grow, the focus of HIV/AIDS treatment has gradually transitioned from urgent care to the management of non-AIDS-related chronic complications and control of chronic inflammation.
Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; China; Continuity of Patient Care; Female; HIV; Humans; Male; National Health Programs; Patient Compliance
PubMed: 31939111
DOI: 10.1007/s11904-019-00478-x -
Journal of Epidemiology and Global... Sep 2021We aimed to assess global trends in Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) and evaluate progress toward eradication since the...
We aimed to assess global trends in Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) and evaluate progress toward eradication since the inception of the pandemic. Data were extracted from the Global Burden of Disease 2019 update and the UNAIDS Data 2019. The datasets included annual figures from 1990 to 2019 for HIV/AIDS in 204 countries and all world regions. We analyzed rates and trends for prevalence, incidence, mortality and disability adjusted life years. Analysis of age and gender distribution in different regions was used to assess demographic changes. Forecasting was used to estimate disease burden up to 2040. Although many countries have witnessed a decrease in the incidence, for Russia, Ukraine, Portugal, Brazil, Spain and the United States, the rates of new cases are rising since 2010. This trend is present even in age-standardized analysis, indicating a rise in excess of population growth. Over 0.5% of the world's population is infected. About 5000 new infections occur daily, of which 500 are children. Mortality rates are falling globally; currently at 11 deaths per 100,000 population, forecasted to decrease to 8.5 deaths by 2040. Prevalence continues to increase, with South Africa, Nigeria, Mozambique, India, Kenya and the United States having the highest burden. The total number as well as the rates of new HIV infections are rising every year in Europe, South America, North America and other regions over the last decade. Maternal-to-child transmission continues at high rates despite effective preventive regimens. There is an urgent need to develop programs to curb the rising incidence of HIV.
Topics: Acquired Immunodeficiency Syndrome; Brazil; Europe; HIV Infections; Humans; North America
PubMed: 34270183
DOI: 10.2991/jegh.k.210621.001 -
Chinese Medical Journal Nov 2021In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world...
In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Topics: Acquired Immunodeficiency Syndrome; China; Disease Outbreaks; HIV Infections; Humans; Prevalence
PubMed: 34759226
DOI: 10.1097/CM9.0000000000001842 -
The Journal of Investigative Dermatology Mar 2022The family of autoinflammatory diseases (AIDs) continues to expand and now includes over 40 genetically defined disorders. Their defining feature is a dysregulated... (Review)
Review
The family of autoinflammatory diseases (AIDs) continues to expand and now includes over 40 genetically defined disorders. Their defining feature is a dysregulated inflammatory innate immune response. Many AIDs have overlapping clinical characteristics, and dermatological manifestations are common. Autoinflammatory features have also been recognized in more common dermatological conditions such as psoriasis. Furthermore, there is an increasing understanding that immunodeficiencies, autoimmune disorders, and even some allergic disorders share overlapping autoinflammatory features. The discovery that certain somatic mutations, arising within the bone marrow and restricted to the myeloid cell lineage can cause acquired AID heralds a new era of discoveries in this field.
Topics: Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Hereditary Autoinflammatory Diseases; Humans; Immunity, Innate; Inflammation
PubMed: 34887082
DOI: 10.1016/j.jid.2021.07.189 -
Annual Review of Pharmacology and... Jan 2023Modern antiretroviral therapy safely, potently, and durably suppresses human immunodeficiency virus (HIV) that, if left untreated, predictably causes acquired... (Review)
Review
Modern antiretroviral therapy safely, potently, and durably suppresses human immunodeficiency virus (HIV) that, if left untreated, predictably causes acquired immunodeficiency syndrome (AIDS), which has been responsible for tens of millions of deaths globally since it was described in 1981. In one of the most extraordinary medical success stories in modern times, a combination of pioneering basic science, innovative drug development, and ambitious public health programming resulted in access to lifesaving, safe drugs, taken as an oral tablet daily, for most of the world. However, substantial challenges remain in the fields of prevention, timely access to diagnosis, and treatment, especially in pediatric and adolescent patients. As HIV-positive adults age, treating their comorbidities will require understanding the course of different chronic diseases complicated by HIV-related and antiretroviral toxicities and finding potential treatments. Finally, new long-acting antiretrovirals on the horizon promise exciting new options in both the prevention and treatment fields.
Topics: Adult; Adolescent; Humans; Child; Anti-HIV Agents; HIV Infections; Acquired Immunodeficiency Syndrome
PubMed: 36662580
DOI: 10.1146/annurev-pharmtox-052020-094321