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1.
Alcohol Use and the Risk of Communicable Diseases.
Morojele, NK, Shenoi, SV, Shuper, PA, Braithwaite, RS, Rehm, J
Nutrients. 2021;(10)
Abstract
The body of knowledge on alcohol use and communicable diseases has been growing in recent years. Using a narrative review approach, this paper discusses alcohol's role in the acquisition of and treatment outcomes from four different communicable diseases: these include three conditions included in comparative risk assessments to date-Human Immunodeficiency Virus (HIV)/AIDS, tuberculosis (TB), and lower respiratory infections/pneumonia-as well as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) because of its recent and rapid ascension as a global health concern. Alcohol-attributable TB, HIV, and pneumonia combined were responsible for approximately 360,000 deaths and 13 million disability-adjusted life years lost (DALYs) in 2016, with alcohol-attributable TB deaths and DALYs predominating. There is strong evidence that alcohol is associated with increased incidence of and poorer treatment outcomes from HIV, TB, and pneumonia, via both behavioral and biological mechanisms. Preliminary studies suggest that heavy drinkers and those with alcohol use disorders are at increased risk of COVID-19 infection and severe illness. Aside from HIV research, limited research exists that can guide interventions for addressing alcohol-attributable TB and pneumonia or COVID-19. Implementation of effective individual-level interventions and alcohol control policies as a means of reducing the burden of communicable diseases is recommended.
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2.
Alcohol Use and Abuse Conspires With HIV Infection to Aggravate Intestinal Dysbiosis and Increase Microbial Translocation in People Living With HIV: A Review.
Yan, J, Ouyang, J, Isnard, S, Zhou, X, Harypursat, V, Routy, JP, Chen, Y
Frontiers in immunology. 2021;:741658
Abstract
The intestinal microbiome is an essential so-called human "organ", vital for the induction of innate immunity, for metabolizing nutrients, and for maintenance of the structural integrity of the intestinal barrier. HIV infection adversely influences the richness and diversity of the intestinal microbiome, resulting in structural and functional impairment of the intestinal barrier and an increased intestinal permeability. Pathogens and metabolites may thus cross the "leaky" intestinal barrier and enter the systemic circulation, which is a significant factor accounting for the persistent underlying chronic inflammatory state present in people living with HIV (PLWH). Additionally, alcohol use and abuse has been found to be prevalent in PLWH and has been strongly associated with the incidence and progression of HIV/AIDS. Recently, converging evidence has indicated that the mechanism underlying this phenomenon is related to intestinal microbiome and barrier function through numerous pathways. Alcohol acts as a "partner" with HIV in disrupting microbiome ecology, and thus impairing of the intestinal barrier. Optimizing the microbiome and restoring the integrity of the intestinal barrier is likely to be an effective adjunctive therapeutic strategy for PLWH. We herein critically review the interplay among HIV, alcohol, and the gut barrier, thus setting the scene with regards to development of effective strategies to counteract the dysregulated gut microbiome and the reduction of microbial translocation and inflammation in PLWH.
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3.
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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The Bacterium Akkermansia muciniphila: A Sentinel for Gut Permeability and Its Relevance to HIV-Related Inflammation.
Ouyang, J, Lin, J, Isnard, S, Fombuena, B, Peng, X, Marette, A, Routy, B, Messaoudene, M, Chen, Y, Routy, JP
Frontiers in immunology. 2020;:645
Abstract
Gut dysbiosis, namely dysregulation of the intestinal microbiota, and increased gut permeability lead to enhanced inflammation and are commonly seen in chronic conditions such as obesity and aging. In people living with HIV (PLWH), several lines of evidence suggest that a depletion of gut CD4 T-cells is associated with gut dysbiosis, microbial translocation and systemic inflammation. Antiretroviral therapy (ART) rapidly controls viral replication, which leads to CD4 T-cell recovery and control of the disease. However, gut dysbiosis, epithelial damage and microbial translocation persist despite ART, increasing risk of developing inflammatory non-AIDS comorbidities such as cardiovascular disease, diabetes mellitus, liver steatosis and cancer. In addition to ART, an emerging research priority is to discover strategies to improve the gut microbial composition and intestinal barrier function. Probiotic interventions have been extensively used with controversial benefits in humans. Encouragingly, within the last decade, the intestinal symbiotic bacterium Akkermansia muciniphila has emerged as the "sentinel of the gut." A lower abundance of A. muciniphila has been shown in diabetic and obese people as well as in PLWH. Interventions with high levels of polyphenols such as tea or diets rich in fruit, the antibiotic vancomycin and the antidiabetic drug metformin have been shown to increase A. muciniphila abundance, contributing to improved metabolic function in diabetic and obese individuals. We hypothesize that gut microbiota rich in A. muciniphila can reduce microbial translocation and inflammation, preventing occurrences of non-AIDS comorbidities in PLWH. To this aim, we will discuss the protective effect of A. muciniphila and its potential applications, paving the way toward novel therapeutic strategies to improve gut health in PLWH.
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5.
HIV and cardiovascular disease.
So-Armah, K, Benjamin, LA, Bloomfield, GS, Feinstein, MJ, Hsue, P, Njuguna, B, Freiberg, MS
The lancet. HIV. 2020;(4):e279-e293
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Abstract
HIV-related cardiovascular disease research is predominantly from Europe and North America. Of the estimated 37·9 million people living with HIV worldwide, 25·6 million live in sub-Saharan Africa. Although mechanisms for HIV-related cardiovascular disease might be the same in all people with HIV, the distribution of cardiovascular disease risk factors varies by geographical location. Sub-Saharan Africa has a younger population, higher prevalence of elevated blood pressure, lower smoking rates, and lower prevalence of elevated cholesterol than western Europe and North America. These variations mean that the profile of cardiovascular disease differs between low-income and high-income countries. Research in, implementation of, and advocacy for risk reduction of cardiovascular disease in the global context of HIV should account for differences in the distribution of traditional cardiovascular disease risk factors (eg, hypertension, smoking), consider non-traditional cardiovascular disease risk factors (eg, access to antiretroviral therapy with more benign cardiovascular disease side effect profiles, indoor air pollution), and encourage the inclusion of relevant risk reduction approaches for cardiovascular disease in HIV-care guidelines. Future research priorities include implementation science to scale up and expand integrated HIV and cardiovascular disease care models, which have shown promise in sub-Saharan Africa; HIV and cardiovascular disease epidemiology and mechanisms in women; and tobacco cessation for people living with HIV.
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6.
Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment.
Lagathu, C, Béréziat, V, Gorwood, J, Fellahi, S, Bastard, JP, Vigouroux, C, Boccara, F, Capeau, J
Expert opinion on drug safety. 2019;(9):829-840
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Abstract
Introduction: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases. Area covered: Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART. Expert opinion: At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.
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Current Strategies for Elimination of HIV-1 Latent Reservoirs Using Chemical Compounds Targeting Host and Viral Factors.
Jean, MJ, Fiches, G, Hayashi, T, Zhu, J
AIDS research and human retroviruses. 2019;(1):1-24
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Abstract
Since the implementation of combination antiretroviral therapy (cART), rates of HIV type 1 (HIV-1) mortality, morbidity, and newly acquired infections have decreased dramatically. In fact, HIV-1-infected individuals under effective suppressive cART approach normal life span and quality of life. However, long-term therapy is required because the virus establish a reversible state of latency in memory CD4+ T cells. Two principle strategies, namely "shock and kill" approach and "block and lock" approach, are currently being investigated for the eradication of these HIV-1 latent reservoirs. Actually, both of these contrasting approaches are based on the use of small-molecule compounds to achieve the cure for HIV-1. In this review, we discuss the recent progress that has been made in designing and developing small-molecule compounds for both strategies.
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Comorbid HIV infection and alcohol use disorders: Converging glutamatergic and dopaminergic mechanisms underlying neurocognitive dysfunction.
Giacometti, LL, Barker, JM
Brain research. 2019;:146390
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Abstract
Alcohol use disorders (AUDs) are highly comorbid with human immunodeficiency virus (HIV) infection, occurring at nearly twice the rate in HIV positive individuals as in the general population. Individuals with HIV who consume alcohol show worse long-term prognoses and may be at elevated risk for the development of HIV-associated neurocognitive disorders. The direction of this relationship is unclear, and likely multifactorial. Chronic alcohol exposure and HIV infection independently promote cognitive dysfunction and further may interact to exacerbate neurocognitive deficits through effects on common targets, including corticostriatal glutamate and dopamine neurotransmission. Additionally, drug and alcohol use is likely to reduce treatment adherence, potentially resulting in accelerated disease progression and subsequent neurocognitive impairment. The development of neurocognitive impairments may further reduce cognitive control over behavior, resulting in escalating alcohol use. This review will examine the complex relationship between HIV infection and alcohol use, highlighting impacts on dopamine and glutamate systems by which alcohol use and HIV act independently and in tandem to alter corticostriatal circuit structure and function to dysregulate cognitive function.
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Transmission of CMV, HTLV-1, and HIV through breastmilk.
Prendergast, AJ, Goga, AE, Waitt, C, Gessain, A, Taylor, GP, Rollins, N, Abrams, EJ, Lyall, EH, de Perre, PV
The Lancet. Child & adolescent health. 2019;(4):264-273
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Abstract
Breastfeeding is a crucial child survival intervention. However, the potential for transmission of viral infections from mother to child presents the dilemma of how best to interpret the benefits and risks of breastfeeding in different settings. In this Review, we compare the transmission dynamics, risk factors, and outcomes of infection with three chronic viruses transmitted through breastmilk: cytomegalovirus, human T-cell lymphotropic virus type 1, and HIV. We provide an overview of intervention approaches and discuss scientific, policy, and programming gaps in the understanding of these major global infections.
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10.
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.