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Acute Promyelocytic Leukemia and HIV: Case Reports and a Review of the Literature.
Kunitomi, A, Hasegawa, Y, Lmamura, J, Yokomaku, Y, Tokunaga, T, Miyata, Y, Iida, H, Nagai, H
Internal medicine (Tokyo, Japan). 2019;(16):2387-2391
Abstract
Acute promyelocytic leukemia (APL) in human immunodeficiency virus (HIV)-infected individuals is very rare. There is currently no consensus regarding the use of anti-cancer drugs with highly active anti-retroviral therapy (ART) in these patients due to their small number. We herein report two cases of APL with HIV-infected patients. Both cases received all-trans-retinoic acid-containing chemotherapies and achieved complete remission. ART was continued throughout the treatment course. The clinical course of these cases suggests that it is preferable to perform standard chemotherapy for APL with ART if patients have an adequate performance status.
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Systemic and cell-specific mechanisms of vasculopathy induced by human immunodeficiency virus and highly active antiretroviral therapy.
Haser, GC, Sumpio, B
Journal of vascular surgery. 2017;(3):849-859
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OBJECTIVE Patients infected with human immunodeficiency virus (HIV) have higher rates of dyslipidemia, atherosclerosis, and chronic inflammation that can damage the vascular system compared with the general population. This can be attributed both to HIV itself and to highly active antiretroviral therapy (HAART) they receive. This review outlines the mechanisms by which HIV and HIV medications can cause vascular complications and identifies strategic areas of research to treat these dysfunctions. REVIEW HIV and HAART affect the vascular system through several mechanisms that target systemic or metabolic systems and specific cells. HIV causes dyslipidemia and chronic immune activation, which can contribute to atherosclerosis. In addition, HIV damages macrophages, endothelial cells, smooth muscle cells, and platelets, and this damage also plays a role in the development of atherosclerosis. HAART, particularly protease inhibitors, interferes with cholesterol metabolism and can affect macrophages, endothelial cells, and smooth muscle cells. The metabolic changes and cell damage induced by HIV and HAART put HIV patients at increased risk for atherosclerosis, dyslipidemia, and serious cardiovascular events such as myocardial infarction and stroke. CONCLUSIONS HIV patients have increased risk of developing potentially life-threatening cardiovascular pathology, which cannot be explained by traditional cardiovascular risk factors alone. More research is needed into therapies to target this HIV-specific vasculopathy.
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A literature review on cardiovascular risk in human immunodeficiency virus-infected patients: implications for clinical management.
Neto, MG, Zwirtes, R, Brites, C
The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases. 2013;(6):691-700
Abstract
INTRODUCTION In recent years, there has been growing concern about an increasing rate of cardiovascular diseases in human immunodeficiency virus-infected patients, which could be associated with side effects of highly active antiretroviral therapy. It is likely that the metabolic disorders related to anti-human immunodeficiency virus treatment will eventually translate into a increased cardiovascular risk in patients submitted to such regimens. OBJECTIVE To evaluate if human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy are at higher risk of cardiovascular diseases than human immunodeficiency virus infected patients not receiving highly active antiretroviral therapy, or the general population. RESEARCH DESIGN AND METHODS We conducted a computer-based search in representative databases, and also performed manual tracking of citations in selected articles. RESULT The available evidence suggests an excess risk of cardiovascular events in human immunodeficiency virus-infected persons compared to non-human immunodeficiency virus infected individuals. The use of highly active antiretroviral therapy is associated with increased levels of total cholesterol, triglycerides, low-density lipoprotein and morphological signs of cardiovascular diseases. Some evidence suggested that human immunodeficiency virus-infected individuals on highly active antiretroviral therapy regimens are at increased risk of dyslipidemia, ischemic heart disease, and myocardial infarction, particularly if the highly active antiretroviral therapy regimen contains a protease inhibitor. CONCLUSION Physicians must weigh the cardiovascular risk against potential benefits when prescribing highly active antiretroviral therapy. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving highly active antiretroviral therapy regimens, particularly for those with known underlying cardiovascular risk factors. A better understanding of the molecular mechanisms responsible for increased risk of cardiovascular diseases in human immunodeficiency virus-infected patients will lead to the discovery of new drugs that will reduce cardiovascular risk in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.
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CROI 2013: Complications of HIV disease, viral hepatitis, and antiretroviral therapy.
Luetkemeyer, AF, Havlir, DV, Currier, JS
Topics in antiviral medicine. 2013;(2):62-74
Abstract
Studies with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) monoinfection and HIV coinfection were highlighted at the 2013 Conference on Retroviruses and Opportunistic Infections (CROI). In HCV monoinfected patients, several interferon alfa-sparing, all-oral regimens demonstrated cure rates of greater than 90% with 12 weeks of treatment, including for hard-to-treat patients. Cure rates of 75% were attained in HIV/HCV coinfected patients with the addition of the investigational HCV protease inhibitor (PI) simeprevir to peginterferon alfa and ribavirin. Drug-drug interaction data to inform safe coadminstration of antiretroviral therapy with DAA-based HCV treatment were presented. There was continued emphasis on pathogenesis, management, and prevention of the long-term complications of HIV disease and its therapies, including cardiovascular disease, renal disease, alterations in bone metabolism, and vitamin D deficiency, along with a growing focus on biomarkers to predict development of end-organ disease. Understanding the elevated risk for non-AIDS-defining malignancies in the HIV-infected population and optimal management was a focal point of this year's data. Finally, the conference provided important information on tuberculosis coinfection and cryptococcal meningitis.
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Acute pancreatitis in HIV/AIDS patients: an issue of concern.
Dragovic, G
Asian Pacific journal of tropical biomedicine. 2013;(6):422-5
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Pancreatitis is a well-described complication of human immunodeficiency virus (HIV) itself and its combination antiretroviral therapy. Historically, this has been predominantly associated with the usage of nucleoside reverse transcriptase inhibitors such as didanosine and stavudine, but only rarely with the usage of protease inhibitors via the induction of hypertriglyceridemia. Pancreatitis rates in HIV/AIDS population may have been exceedingly high because of the comorbid conditions prevalent in HIV/AIDS patients (e.g. ethanol use and biliary disease), and the use of non-combination antiretroviral therapy medications such as pentamidine, corticosteroids, ketoconazole, sulphonamides, metronidazole, isoniazid and opportunistic infections (e.g. cytomegalovirus, cryptosporidiosis, mycobacterial disease). In resource limited settings, where didanosine and stavudine are widely available in cheaper generic fixed dose combinations it is likely that their usage will remain in the first line HIV treatment in common. In such settings management or estimation of a patient's risk of pancreatitis still remains an issue of concern.
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Complications of HIV disease and antiretroviral therapy.
Luetkemeyer, AF, Havlir, DV, Currier, JS
Topics in antiviral medicine. 2012;(2):48-60
Abstract
Studies on the efficacy of and drug interactions with the hepatitis C virus (HCV) direct-acting antivirals (DAAs) in HCV/ HIV coinfection were a highlight of the 2012 Conference on Retroviruses and Opportunistic Infections. The addition of an HCV protease inhibitor (PI) to pegylated interferon alfa/ribavirin increased HCV cure rates by 30% to 35% in HCV genotype 1 treatment-naive HIV-coinfected patients, an increase similar to that observed in HIV-uninfected HCV-infected patients. Drug interactions with antiretrovirals can be complex, and DAAs are recommended for use only with antiretroviral drugs for which pharmacokinetic data are available. Further drug interaction and clinical data are needed to ensure the safe coadminstration of DAAs with antiretroviral therapy. The conference placed continued emphasis on pathogenesis, management, and prevention of the long-term complications of HIV disease and its therapies, including cardiovascular disease, lipodystrophy, renal disease, alterations in bone metabolism, and vitamin D deficiency, along with a growing focus on biomarkers to predict development of end-organ disease. HIV has increasingly been recognized as a disease of accelerated aging, manifested by increased progression of vascular disease, cellular markers of aging, and a heightened risk of certain non-AIDS-defining malignancies. This year's conference also highlighted data on diagnosis, prevention, and complications of tuberculosis coinfection as well as the treatment and prevention of coinfections that are common with HIV, including cryptococcal meningitis, influenza, and varicella zoster.
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Nutrition and disease progression pre-highly active antiretroviral therapy (HAART) and post-HAART: can good nutrition delay time to HAART and affect response to HAART?
Chandrasekhar, A, Gupta, A
The American journal of clinical nutrition. 2011;(6):1703S-1715S
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Several studies have investigated a variety of nutritional supplementation interventions in adults with HIV. In this narrative review, we summarize the evidence from 31 clinical trials that explore clinical benefits of macronutrient and micronutrient supplementation in this population while attempting to answer the question of whether good nutrition can delay the time to highly active antiretroviral therapy (HAART) initiation and response. We focused on trials published in English between 1990 and 2010 that reported on CD4 count, viral load, and disease progression or survival. Among 9 macronutrient and 22 micronutrient trials, we found that evidence for improved CD4 count and HIV viral load with nutritional supplementation was limited; only 11.1% and 36.8% of macronutrient and micronutrient supplementation trials, respectively, reported improved CD4 count; and 33.3% and 12.5% of macronutrient and micronutrient trials, respectively, reported decreased viral load. Given their utility as surrogate markers of HIV disease progression, this suggests limited evidence for nutritional interventions having an impact on delaying HAART initiation or on improving HAART response. However, there are challenges in evaluating the effects of nutritional supplementation on clinical disease in that comparisons are difficult due to heterogeneity in study design, patient population, nutrient doses and combinations, baseline levels of deficiency, and study endpoints, including lack of clarity in defining and reporting HAART status. Future studies need to adopt a more rigorous standard design with adequate power and follow-up and require a consensus on composition and dose of nutrient interventions to be tested to more specifically answer the question on the impact of nutritional interventions on HIV disease progression and HAART response.
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Human immunodeficiency virus & cardiovascular risk.
Barbaro, G, Barbarini, G
The Indian journal of medical research. 2011;(6):898-903
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Highly active antiretroviral therapy (HAART) significantly changed the prevalence of the cardiovascular manifestations of human immunodeficiency virus (HIV)/AIDS. In developed countries, a 30 per cent reduction in the prevalence of cardiomyopathy and pericardial effusion was observed, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited, and the pathogenic impact of nutritional factors is significant, a 32 per cent increase was seen in the prevalence of cardiomyopathy and related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause, in a high proportion of HIV-infected patients, a lipodystrophy syndrome that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving HAART regimens, particularly for those with known underlying cardiovascular risk factors, according to the most recent clinical guidelines.
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Cardiovascular complications in the acquired immunodeficiency syndrome.
Barbaro, G, Silva, EF
Revista da Associacao Medica Brasileira (1992). 2009;(5):621-30
Abstract
The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease, with increased survival rates. However, the introduction of HAART has generated a contrast in the cardiac manifestations of AIDS. In developed countries, we observed an approximate 30% reduction in the prevalence of HIV-associated cardiomyopathy, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited and the pathogenic impact of nutritional factors is significant, we observed an increase of approximately 32% in the prevalence of HIV-associated cardiomyopathy and a related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, have been shown to cause, in a high proportion of HIV-infected patients, a iatrogenic metabolic syndrome (HIV-lipodystrophy syndrome).This is associated with an increased risk of atherosclerosis-related cardiovascular events even in young HIV-infected people. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce cardiovascular risk in HIV-infected patients receiving HAART.
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Idiopathic AIDS enteropathy and treatment of gastrointestinal opportunistic pathogens.
Cello, JP, Day, LW
Gastroenterology. 2009;(6):1952-65
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Diarrhea in patients with acquired immune deficiency syndrome (AIDS) has proven to be both a diagnostic and treatment challenge since the discovery of the human immunodeficiency virus (HIV) virus more than 30 years ago. Among the main etiologies of diarrhea in this group of patients are infectious agents that span the array of viruses, bacteria, protozoa, parasites, and fungal organisms. In many instances, highly active antiretroviral therapy remains the cornerstone of therapy for both AIDS and AIDS-related diarrhea, but other targeted therapies have been developed as new pathogens are identified; however, some infections remain treatment challenges. Once identifiable infections as well as other causes of diarrhea are investigated and excluded, a unique entity known as AIDS enteropathy can be diagnosed. Known as an idiopathic, pathogen-negative diarrhea, this disease has been investigated extensively. Atypical viral pathogens, including HIV itself, as well as inflammatory and immunologic responses are potential leading causes of it. Although AIDS enteropathy can pose a diagnostic challenge so too does the treatment of it. Highly active antiretroviral therapy, nutritional supplementation, electrolyte replacements, targeted therapy for infection if indicated, and medications for symptom control all are key elements in the treatment regimen. Importantly, a multidisciplinary approach among the gastroenterologist, infectious disease physician, HIV specialists, oncology, and surgery is necessary for many patients.