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Lean Mass Improvement from Nutrition Education and Protein Supplementation among Rural Indian Women Living with HIV/AIDS: Results from Cluster Randomized Factorial Trial at 18-Month Follow-Up.
Carpenter, CL, Kapur, K, Ramakrishna, P, Pamujula, S, Yadav, K, Giovanni, JE, Julian, O, Ekstrand, ML, Sinha, S, Nyamathi, AM
Nutrients. 2021;(1)
Abstract
Loss of lean muscle mass impairs immunity and increases mortality risk among individuals with HIV/AIDS. We evaluated the relative contributions of protein supplementation and nutrition education on body composition among 600 women living with HIV/AIDS in rural Andhra Pradesh, India. We conducted a cluster randomized controlled 2 × 2 factorial trial lasting six months with follow up at twelve and eighteen months. Interventions occurred in the Nellore and Prakasam regions of Andhra Pradesh by trained village women, ASHA (Accredited Social Health Activists), and included: (1) the usual supportive care from ASHA (UC); (2) UC plus nutrition education (NE); (3) UC plus nutritional protein supplementation (NS); (4) combined UC plus NE plus NS. A Bioimpedance Analyzer Model 310e measured body composition. SAS 9.4 analyzed all data. Mixed models using repeated measures evaluated lean mass change from baseline as primary and fat weight and total weight as secondary outcomes. Lean mass change was significantly associated with NS (p = 0.0001), NE (p = 0.0001), and combined NS plus NE (p = 0.0001), with similar associations for secondary outcomes. Stronger associations for total weight were observed with greater ART adherence. Nutritional interventions may improve physiologic response to HIV. Significant increases in lean mass resulted from independent and combined protein supplementation and nutrition education.
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Severe acute hypokalaemia associated with piperacillin/tazobactam in an HIV-infected patient under antiretroviral therapy with tenofovir alafenamide: case report and literature review.
Tai, CC, Chou, RY, Guo, JY, Chen, HP
Sexual health. 2020;(2):194-197
Abstract
Piperacillin/tazobactam is a commonly prescribed antimicrobial agent. Tenofovir alafenamide (TAF) is increasingly being used in antiretroviral therapy (ART) of HIV. Herein we report a case of a 57-year-old male with AIDS receiving TAF-containing ART in whom severe refractory hypokalaemia developed after coadministration of piperacillin/tazobactam for suspected hospital-acquired infection. Upon withdrawal of piperacillin/tazobactam, serum potassium concentrations returned to normal within 2 days. Hypokalaemia is a rare adverse effect of piperacillin/tazobactam and may be aggravated with the underlying use of TAF. We also reviewed past reported cases of hypokalaemia after piperacillin/tazobactam administration. We want to highlight that a more cautious approach should be considered when combining piperacillin/tazobactam and TAF in clinical practice.
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Factors associated with antiretroviral therapy adherence in adults: an integrative review of literature.
Carvalho, PP, Barroso, SM, Coelho, HC, Penaforte, FRO
Ciencia & saude coletiva. 2019;(7):2543-2555
Abstract
AIDS is an advanced clinical manifestation of HIV infection. It generates severe immunodeficiency and associated infections that may lead to death. The antiretroviral therapy (ART) has reduced the morbimortality of HIV/AIDS, but its benefits depend on ART adherence. This integrative review followed the PICO method to identify factors associated with adult adherence to ART. Empirical papers published between January 2010 and December 2016 in the Medline, SciELO, Lilacs and PePSIC databases were included. We analyzed 125 papers regarding the characteristics of studies, adherence measures and associated factors. Results showed a wide variety in the definition of adherence and the use of measures for its monitoring, as well as several adherence-associated factors. These were categorized as follows: 1- Individual variables; 2- Treatment characteristics; 3- HIV/aids infection characteristics; 4- Relationship with the health services; 5- Social support. Health services should characterize the users' profiles, systematize adherence measures and regionally assess adherence-associated factors for the early detection of non-adherence to ART and implementation of effective intervention plans.
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Heparin and heparan sulfate proteoglycans promote HIV-1 p17 matrix protein oligomerization: computational, biochemical and biological implications.
Bugatti, A, Paiardi, G, Urbinati, C, Chiodelli, P, Orro, A, Uggeri, M, Milanesi, L, Caruso, A, Caccuri, F, D'Ursi, P, et al
Scientific reports. 2019;(1):15768
Abstract
p17 matrix protein released by HIV+ cells interacts with leukocytes heparan sulfate proteoglycans (HSPGs), CXCR1 and CXCR2 exerting different cytokine-like activities that contribute to AIDS pathogenesis. Since the bioactive form of several cytokines is represented by dimers/oligomers and oligomerization is promoted by binding to heparin or HSPGs, here we evaluated if heparin/HSPGs also promote p17 oligomerization. Heparin favours p17 dimer, trimer and tetramer assembly, in a time- and biphasic dose-dependent way. Heparin-induced p17 oligomerization is of electrostatic nature, being it prevented by NaCl, by removing negative sulfated groups of heparin and by neutralizing positive lysine residues in the p17 N-terminus. A new computational protocol has been implemented to study heparin chains up to 24-mer accommodating a p17 dimer. Molecular dynamics show that, in the presence of heparin, two p17 molecules undergo conformational modifications creating a continuous "electropositive channel" in which heparin sulfated groups interact with p17 basic amino acids, promoting its dimerization. At the cell surface, HSPGs induce p17 oligomerization, as demonstrated by using B-lymphoblastoid Namalwa cells overexpressing the HSPG Syndecan-1. Also, HSPGs on the surface of BJAB and Raji human B-lymphoblastoid cells are required to p17 to induce ERK1/2 activation, suggesting that HS-induced oligomerization plays a role in p17-induced lymphoid dysregulation during AIDS.
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Nutritional Issues and Positive Living in Human Immunodeficiency Virus/AIDS.
Clark, WA, Cress, EM
The Nursing clinics of North America. 2018;(1):13-24
Abstract
Nutritional counseling has been shown to improve dietary intake in individuals with human immunodeficiency virus (HIV)/AIDS. Registered dietitians/nutritionists can individualize diet interventions to optimize effectiveness in treating metabolic consequences of the HIV infection or highly active antiretroviral therapy. Nutrition management for individuals infected with HIV can be helpful in maintaining lean body weight, combating oxidative stress, reducing complications from hyperglycemia and hyperlipidemia, and managing gastrointestinal function. Consideration should be given to including the expertise of a registered dietitian/nutritionist.
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Vitamin D, D-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study.
Musselwhite, LW, Andrade, BB, Ellenberg, SS, Tierney, A, Belaunzaran-Zamudio, PF, Rupert, A, Lederman, MM, Sanne, I, Sierra Madero, JG, Sereti, I
EBioMedicine. 2016;:115-23
Abstract
To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.
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Nucleocapsid Protein: A Desirable Target for Future Therapies Against HIV-1.
Mori, M, Kovalenko, L, Lyonnais, S, Antaki, D, Torbett, BE, Botta, M, Mirambeau, G, Mély, Y
Current topics in microbiology and immunology. 2015;:53-92
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Abstract
The currently available anti-HIV-1 therapeutics is highly beneficial to infected patients. However, clinical failures occur as a result of the ability of HIV-1 to rapidly mutate. One approach to overcome drug resistance is to target HIV-1 proteins that are highly conserved among phylogenetically distant viral strains and currently not targeted by available therapies. In this respect, the nucleocapsid (NC) protein, a zinc finger protein, is particularly attractive, as it is highly conserved and plays a central role in virus replication, mainly by interacting with nucleic acids. The compelling rationale for considering NC as a viable drug target is illustrated by the fact that point mutants of this protein lead to noninfectious viruses and by the inability to select viruses resistant to a first generation of anti-NC drugs. In our review, we discuss the most relevant properties and functions of NC, as well as recent developments of small molecules targeting NC. Zinc ejectors show strong antiviral activity, but are endowed with a low therapeutic index due to their lack of specificity, which has resulted in toxicity. Currently, they are mainly being investigated for use as topical microbicides. Greater specificity may be achieved by using non-covalent NC inhibitors (NCIs) targeting the hydrophobic platform at the top of the zinc fingers or key nucleic acid partners of NC. Within the last few years, innovative methodologies have been developed to identify NCIs. Though the antiviral activity of the identified NCIs needs still to be improved, these compounds strongly support the druggability of NC and pave the way for future structure-based design and optimization of efficient NCIs.
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HIV/AIDS and lipodystrophy: implications for clinical management in resource-limited settings.
Finkelstein, JL, Gala, P, Rochford, R, Glesby, MJ, Mehta, S
Journal of the International AIDS Society. 2015;(1):19033
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Abstract
INTRODUCTION Lipodystrophy is a term used to describe a metabolic complication of fat loss, fat gain, or a combination of fat loss and gain, which is associated with some antiretroviral (ARV) therapies given to HIV-infected individuals. There is limited research on lipodystrophy in low- and middle-income countries, despite accounting for more than 95% of the burden of HIV/AIDS. The objective of this review was to evaluate the prevalence, pathogenesis and prognosis of HIV-related lipoatrophy, lipohypertrophy and mixed syndrome, to inform clinical management in resource-limited settings. METHODS We conducted a structured literature search using MEDLINE electronic databases. Relevant MeSH terms were used to identify published human studies on HIV and lipoatrophy, lipohypertrophy, or mixed syndrome in low-, low-middle- and upper-middle-income countries through 31 March 2014. The search resulted in 5296 articles; after 1599 studies were excluded (958 reviews, 641 non-human), 3697 studies were extracted for further review. After excluding studies conducted in high-income settings (n=2808), and studies that did not meet inclusion criteria (n = 799), 90 studies were included in this review. RESULTS AND DISCUSSION Of the 90 studies included in this review, only six were from low-income countries and eight were from lower middle-income economies. These studies focused on lipodystrophy prevalence, risk factors and side effects of antiretroviral therapy (ART). In most studies, lipodystrophy developed after the first six months of therapy, particularly with the use of stavudine. Lipodystrophy is associated with increased risk of cardiometabolic complications. This is disconcerting and anticipated to increase, given the rapid scale-up of ART worldwide, the increasing number and lifespan of HIV-infected patients on long-term therapy, and the emergence of obesity and non-communicable diseases in settings with extensive HIV burden. CONCLUSIONS Lipodystrophy is common in resource-limited settings, and has considerable implications for risk of metabolic diseases, quality of life and adherence. Comprehensive evidence-based interventions are urgently needed to reduce the burden of HIV and lipodystrophy, and inform clinical management in resource-limited settings.
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Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs.
Spadoni, JL, Rucart, P, Le Clerc, S, van Manen, D, Coulonges, C, Ulveling, D, Laville, V, Labib, T, Taing, L, Delaneau, O, et al
PloS one. 2015;(9):e0136989
Abstract
BACKGROUND Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS. METHODS We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate. RESULTS Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV.
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Orbital manifestations in patients with acquired immunodeficiency syndrome.
Sodhi, PK
Nepalese journal of ophthalmology : a biannual peer-reviewed academic journal of the Nepal Ophthalmic Society : NEPJOPH. 2014;(2):205-19
Abstract
INTRODUCTION The orbital manifestations of acquired immunodeficiency syndrome(AIDS) are uncommon. OBJECTIVE To provide a review of orbital manifestations of AIDS, the predisposing factors, investigations, treatment and outcome. MATERIALS AND METHODS Meticulous and systematic literature search of Pubmed to identify manuscripts describing orbital manifestations of AIDS was done and the articles were reviewed.The keywords used in the search were “orbit and AIDS”, “HIV positive and orbit”,“orbit manifestations in AIDS”, “orbital disease and AIDS” and “orbital infections and AIDS”. The orbital involvement in AIDS may present with opportunistic infections from organisms like fungi, viruses, bacteria and protozoa or with malignancies like Kaposi’s sarcoma, squamous cell carcinoma, smooth muscle cell tumors and lymphoma.The predisposing factors for orbital involvement in AIDS are low CD4+ cell count and the immunosuppressive states like diabetes, diabetic ketoacidosis, intravenous drug abuse and neutropenia. A patient may present with fever, headache, nausea, vomiting,decreased vision, ocular pain, and, in cases of mass formation, there is periorbital swelling, axial proptosis, globe displacement and swollen optic disc. Radiologically,mass formation, orbital bony destruction, and spread of disease to contiguous structures including the central nervous system may be seen. The medical management includes therapy for infection and HIV-1 protease inhibitors (highly active antiretroviral therapy)to suppress HIV-1 replication. For tumors, radical surgery including debulking followed by postoperative radiotherapy is generally needed. CONCLUSION Orbital involvements with AIDS in any form, infective or malignancy, causes significant morbidity and mortality and should be diagnosed and managed as early as possible.