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1.
Review on the Alteration of Gut Microbiota: The Role of HIV Infection and Old Age.
Ashuro, AA, Lobie, TA, Ye, DQ, Leng, RX, Li, BZ, Pan, HF, Fan, YG
AIDS research and human retroviruses. 2020;(7):556-565
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Abstract
Human immunodeficiency virus (HIV) infection results in gut microbiota alteration and this is associated with immune activation and chronic inflammation. The gastrointestinal tract is a primary site of viral replication and thus HIV-induced loss of T-helper (Th) cells in the gut causes impairments in intestinal barriers, resulting in disruptions in intestinal immunity and precipitating into gut dysbiosis. Here, we show that late HIV diagnosis can negatively affect the immunological, virological, and clinical prognosis of the patients with its higher implication at an older age. Further, the review indicates that antiretroviral therapy affects the gut microbiota. We discussed the use of probiotics and prebiotics that have been indicated to play a promising role in reversing gut microbiota alteration in HIV patients. Though there are several studies reported with regard to such alterations in gut microbiota regarding HIV infection, there is a need to provide comprehensive updates. It is, therefore, the objective of this review to present most recently available evidence on the alteration of gut microbiota among HIV patients.
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2.
The Potential Protective Role of Vitamin D Supplementation on HIV-1 Infection.
Alvarez, N, Aguilar-Jimenez, W, Rugeles, MT
Frontiers in immunology. 2019;:2291
Abstract
HIV infection remains a global and public health issue with the incidence increasing in some countries. Despite the fact that combination antiretroviral therapy (cART) has decreased mortality and increased the life expectancy of HIV-infected individuals, non-AIDS conditions, mainly those associated with a persistent inflammatory state, have emerged as important causes of morbidity, and mortality despite effective antiviral therapy. One of the most common comorbidities in HIV-1 patients is Vitamin D (VitD) insufficiency, as VitD is a hormone that, in addition to its physiological role in mineral metabolism, has pleiotropic effects on immune regulation. Several reports have shown that VitD levels decrease during HIV disease progression and correlate with decreased survival rates, highlighting the importance of VitD supplementation during infection. An extensive review of 29 clinical studies of VitD supplementation in HIV-infected patients showed that regardless of cART, when VitD levels were increased to normal ranges, there was a decrease in inflammation, markers associated with bone turnover, and the risk of secondary hyperparathyroidism while the anti-bacterial response was increased. Additionally, in 3 of 7 studies, VitD supplementation led to an increase in CD4+ T cell count, although its effect on viral load was inconclusive since most patients were on cART. Similarly, previous evidence from our laboratory has shown that VitD can reduce the infection of CD4+ T cells in vitro. The effect of VitD supplementation on other HIV-associated conditions, such as cardiovascular diseases, dyslipidemia or hypertension, warrants further exploration. Currently, the available evidence suggests that there is a potential role for VitD supplementation in people living with HIV-1, however, comprehensive studies are required to define an adequate supplementation protocol for these individuals.
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Use of (1→3)-β-d-glucan for diagnosis and management of invasive mycoses in HIV-infected patients.
Farhour, Z, Mehraj, V, Chen, J, Ramendra, R, Lu, H, Routy, JP
Mycoses. 2018;(10):718-722
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Abstract
People living with HIV (PLHIV) are highly vulnerable to invasive fungal infections (IFIs) due to their immune dysfunction. Diagnosis and treatment of IFIs remain challenging due to the requirement of deep tissue sampling to visualise and culture fungi before initiating treatment. Such techniques are less practical in resource-limited settings due to their cost and requirement of relatively invasive procedures. Hence, identification of surrogate markers for the early diagnosis and therapeutic monitoring of IFIs is required. Recent studies have shown that (1→3)-β-d-glucan (BDG), a major fungal cell wall antigen, represents a promising soluble marker for the presumptive diagnosis and therapeutic monitoring of IFIs in HIV-infected patients. Herein, we review findings on the merits of BDG assays in the diagnosis of IFIs and monitoring of antifungal therapies for PLHIV. Conversely to other types of immunocompromised patients, HIV infection is associated with gut damage and subsequent bacterial and fungal translocation leading to elevated BDG plasma levels.
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Inclusion body myositis and human immunodeficiency virus type 1: A new case report and literature review.
Couture, P, Malfatti, E, Morau, G, Mathian, A, Cohen-Aubart, F, Nielly, H, Amoura, Z, Cherin, P
Neuromuscular disorders : NMD. 2018;(4):334-338
Abstract
Prevalence of muscle disease in human immunodeficiency virus (HIV) infection is less than 1% of patients with acquired immune deficiency syndrome. Sporadic inclusion body myositis (IBM) is observed in a few cases of patients infected by retroviruses such as HIV-1. A Caucasian man was diagnosed with HIV when he was 30 years old. The viral load was undetectable and CD4 cell count was 600/mm3 when the diagnosis of inclusion body myositis was confirmed. Histological findings were typical of IBM. The treatment consisted of immunoglobulin therapy for three years without effect. Twenty-two patients were found in the English and French literature. They are younger than those who suffer from IBM without HIV (median age = 47, range: 30 to 59), and they are mostly men with considerable serum creatine kinase (CK) elevation (median CK level = 1322 IU/L, range: 465 to 10270), most of them were treated with Zidovudine.
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Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV-Infected Immunocompromised Patients with Pneumocystis jirovecii Pneumonia.
Salzer, HJF, Schäfer, G, Hoenigl, M, Günther, G, Hoffmann, C, Kalsdorf, B, Alanio, A, Lange, C
Respiration; international review of thoracic diseases. 2018;(1):52-65
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Abstract
The substantial decline in the Pneumocystis jirovecii pneumonia (PCP) incidence in HIV-infected patients after the introduction of antiretroviral therapy (ART) in resource-rich settings and the growing number of non-HIV-infected immunocompromised patients at risk leads to considerable epidemiologic changes with clinical, diagnostic, and treatment consequences for physicians. HIV-infected patients usually develop a subacute course of disease, while non-HIV-infected immunocompromised patients are characterized by a rapid disease progression with higher risk of respiratory failure and higher mortality. The main symptoms usually include exertional dyspnea, dry cough, and subfebrile temperature or fever. Lactate dehydrogenase may be elevated. Typical findings on computed tomography scans of the chest are bilateral ground-glass opacities with or without cystic lesions, which are usually associated with the presence of AIDS. Empiric treatment should be initiated as soon as PCP is suspected. Bronchoalveolar lavage has a higher diagnostic yield compared to induced sputum. Immunofluorescence is superior to conventional staining. A combination of different diagnostic tests such as microscopy, polymerase chain reaction, and (1,3)-β-D-glucan is recommended. Trimeth-oprim/sulfamethoxazole for 21 days is the treatment of choice in adults and children. Alternative treatment regimens include dapsone with trimethoprim, clindamycin with primaquine, atovaquone, or pentamidine. Patients with moderate to severe disease should receive adjunctive corticosteroids. In newly diagnosed HIV-infected patients with PCP, ART should be initiated as soon as possible. In non-HIV-infected immunocompromised patients, improvement of the immune status should be discussed (e.g., temporary reduction of immunosuppressive agents). PCP prophylaxis is effective and depends on the immune status of the patient and the underlying immunocompromising disease.
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6.
Microbiota and Probiotics in Health and HIV Infection.
D'Angelo, C, Reale, M, Costantini, E
Nutrients. 2017;(6)
Abstract
Microbiota play a key role in various body functions, as well as in physiological, metabolic, and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Evidence indicates that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that reside on the mucosal surface or within the mucus layer interact with the host immune system, thus, a healthy gut microbiota is essential for the development of mucosal immunity. In patients with human immunodeficiency virus (HIV), including those who control their disease with antiretroviral drugs (ART), the gut microbiome is very different than the microbiome of those not infected with HIV. Recent data suggests that, for these patients, dysbiosis may lead to a breakdown in the gut's immunologic activity, causing systemic bacteria diffusion and inflammation. Since in HIV-infected patients in this state, including those in ART therapy, the treatment of gastrointestinal tract disorders is frustrating, many studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition, and microbial translocation. This mini-review analyzed the use of probiotics to prevent and attenuate several gastrointestinal manifestations and to improve gut-associated lymphoid tissue (GALT) immunity in HIV infection.
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The therapeutic landscape of HIV-1 via genome editing.
Kwarteng, A, Ahuno, ST, Kwakye-Nuako, G
AIDS research and therapy. 2017;(1):32
Abstract
Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR-Cas9) are transforming the therapeutic landscape of HIV-1. TALENS and ZFNS are structurally similar modular systems, which consist of a FokI endonuclease fused to custom-designed effector proteins but have been largely limited, particularly ZFNs, due to their complexity and cost of protein engineering. However, the newly developed CRISPR-Cas9 system, consists of a single guide RNA (sgRNA), which directs a Cas9 endonuclease to complementary target sites, and serves as a superior alternative to the previous protein-based systems. The techniques have been successfully applied to the development of better HIV-1 models, generation of protective mutations in endogenous/host cells, disruption of HIV-1 genomes and even reactivating latent viruses for better detection and clearance by host immune response. Here, we focus on gene editing-based HIV-1 treatment and research in addition to providing perspectives for refining these techniques.
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Sex Differences in Select Non-communicable HIV-Associated Comorbidities: Exploring the Role of Systemic Immune Activation/Inflammation.
Raghavan, A, Rimmelin, DE, Fitch, KV, Zanni, MV
Current HIV/AIDS reports. 2017;(6):220-228
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Abstract
PURPOSE OF THE REVIEW The goals of this review are to (1) explore HIV-associated cardiovascular disease (CVD), neurocognitive impairment, and non-AIDS-defining cancers (NADC) as heterogeneous model disease states fuelled in part by systemic immune activation/inflammation; (2) consider sex differences in the epidemiology of these diseases in both high-resource and lower-resource settings; and (3) examine biological and environmental factors which may contribute to heightened systemic immune activation/inflammation specifically among women living with HIV (WLHIV). RECENT FINDINGS The observation that WLHIV have higher levels of systemic immune activation/inflammation than men living with HIV (MLHIV) may be relevant to sex differences in select non-communicable HIV-associated comorbidities. Heightened systemic immune activation among WLHIV may be influenced by sex-specific responses to the virus and to immunomodulatory agents, as well as by behavioral choices/comorbid conditions and perturbations in the hypothalamic-pituitary-gonadal axis. Additional research is needed to elucidate region-specific drivers of heightened systemic immune activation/inflammation among WLHIV and to determine whether WLHIV who present with one immune-mediated HIV-associated comorbidity (e.g., cognitive impairment) may be at increased risk for another (e.g., CVD, NADC). This kind of research would facilitate improved risk prediction for non-communicable HIV-associated comorbidities among WLHIV and the development of targeted immunomodulatory prevention strategies.
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9.
Statins in HIV-Infected Patients: Potential Beneficial Effects and Clinical Use.
Bernal, E, Marín, I, Masiá, M, Gutiérrez, F
AIDS reviews. 2017;(2):59-71
Abstract
Patients living with HIV have an increased risk of cardiovascular disease that is considered to be the result of an interaction between traditional cardiovascular risk factors, particularly smoking and dyslipidemia, and persistent chronic inflammation and immune activation associated with HIV infection, along with side effects of antiretroviral therapy. In the general population, the administration of statins has been associated with a reduction in cardiovascular disease-associated mortality, and these drugs are among the most common class of medication prescribed in high-income countries. The beneficial effect of statins extends beyond reducing cholesterol levels as they have been shown to have anti- inflammatory, antithrombotic, antioxidant, immunomodulatory, and vasodilatory effects, and to improve endothelial function. Despite the widespread use of statins in the general population, cohort studies show that these drugs are underutilized in HIV-infected patients, probably due to safety concerns by clinicians and limited data evaluating clinical outcomes in patients on antiretroviral therapy. In this article we review and update the most important clinical studies of statins in HIV- infected patients, describe their side effects and interaction profiles, and discuss the anti-atherosclerotic and pleiotropic effects of these drugs. Finally, we propose recommendations for clinical use of statins in patients living with HIV.
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10.
Cardiovascular disease risk among women living with HIV in North America and Europe.
Stone, L, Looby, SE, Zanni, MV
Current opinion in HIV and AIDS. 2017;(6):585-593
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Abstract
PURPOSE OF REVIEW To examine the epidemiology and mechanistic underpinnings of heightened cardiovascular disease (CVD) risk among women living with HIV (WLHIV) in North America and Europe. RECENT FINDINGS WLHIV in North America and Europe exhibit high CVD incidence rates, which are at par with those of compatriot men living with HIV. Compared with uninfected women, WLHIV in these regions face a 2-4-fold increased relative risk for myocardial infarction, stroke, and heart failure. HIV-associated CVD risk is fuelled by a negative synergy of traditional cardiometabolic risk factors and heightened systemic immune activation/inflammation. Among WLHIV, female sex and endogenous sex hormone production influence both traditional cardiometabolic risk factors and patterns of systemic immune activation/inflammation. WLHIV in North America and Europe may also experience heightened CVD risk in relation to a relatively increased prevalence of behavioral and psychosocial CVD risk factors, coupled with suboptimal therapeutic targeting of known traditional cardiometabolic risk factors. SUMMARY Additional research on sex-specific mechanisms of HIV-associated CVD - based not only out of North America and Europe but also and especially out of Africa, Asia, and South America - will inform the development of CVD prediction algorithms and prevention guidelines clinically relevant to the approximately 17 million women aging with HIV globally.