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Antiretroviral resistance

Lucie Cluver, Franziska Meinck, Elona Toska, F Mark Orkin, Rebecca J Hodes, Lorraine Sherr
OBJECTIVE(S): HIV-positive adolescents have low ART-adherence, with consequent increased risks of mortality, morbidity and viral resistance. Despite high rates of violence against children in the Africa region, no known studies have tested impacts on HIV-positive adolescents. We examine associations of ART-adherence with adolescent violence victimisation by caregivers, teachers, peers, community members, and healthcare providers. DESIGN AND METHODS: HIV-positive adolescents were interviewed (n = 1060), and clinic biomarker data collected...
March 15, 2018: AIDS
Kennedy Daniel Mwambete, Mathias Eulambius
OBJECTIVES: The study aimed to determine the prevalence of otitis media (OM)-associated bacterial flora of asymptomatic people living with HIV (PLH) on antiretroviral therapy (ART) and assess antibiotic resistance profiles of the bacteria. METHODOLOGY: Ear secretion specimens were collected by syringe or cotton swabs. Isolated bacteria were subjected to antibiotic sensitivity tests. RESULTS: Of 290 recruited PLH, 81.7% were females and 18...
January 2018: Journal of the International Association of Providers of AIDS Care
Dimitrios Pilalas, Lemonia Skoura, Apostolia Margariti, Fani Chatzopoulou, Dimitrios Chatzidimitriou, Olga Tsachouridou, Pantelis Zebekakis, Simeon Metallidis, Maria Papaioannou
OBJECTIVES: Despite successful virological suppression, HIV transcription frequently persists intracellularly. In this study, we hypothesize that HIV persistent transcription(HIVpt) may affect to a different extent patients on stable efavirenz(EFV) versus atazanavir(ATV)-based regimens. The role of the expression of drug efflux transporters in HIVpt was also investigated. METHODS: We prospectively enrolled 51 virologically suppressed patients on first-line treatment for one year with EFV or ATV combined with emtricitabine and tenofovir and followed them up for one year...
2018: PloS One
Sonia de Castro, María-José Camarasa
HIV infection still has a serious health and socio-economical impact and is one of the primary causes of morbidity and mortality all over the world. HIV infection and the AIDS pandemic are still matters of great concern, especially in less developed countries where the access to highly active antiretroviral therapy (HAART) is limited. Patient compliance is another serious drawback. Nowadays, HAART is the treatment of choice although it is not the panacea. Despite the fact that it suppresses viral replication at undetectable viral loads and prevents progression of HIV infection into AIDS HAART has several pitfalls, namely, long-term side-effects, drug resistance development, emergence of drug-resistant viruses, low compliance and the intolerance of some patients to these drugs...
March 5, 2018: European Journal of Medicinal Chemistry
Muge Cevik, Chloe Orkin
PURPOSE OF REVIEW: In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. RECENT FINDINGS: In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes...
March 9, 2018: Current Opinion in HIV and AIDS
V T Valuev-Elliston, S N Kochetkov
Highly active antiretroviral therapy (HAART) is one of the most effective means for fighting against HIV-infection. HAART primarily targets HIV-1 reverse transcriptase (RT), and 14 of 28 compounds approved by the FDA as anti-HIV drugs act on this enzyme. HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) hold a special place among HIV RT inhibitors owing to their high specificity and unique mode of action. Nonetheless, these drugs show a tendency to decrease their efficacy due to high HIV-1 variability and formation of resistant virus strains tolerant to clinically applied HIV NNRTIs...
December 2017: Biochemistry. Biokhimii︠a︡
Harshana S De Silva Feelixge, Daniel Stone, Pavitra Roychoudhury, Martine Aubert, Keith R Jerome
Chronic viral infections remain a major public health issue affecting millions of people worldwide. Highly active antiviral treatments have significantly improved prognosis and infection-related morbidity and mortality, but have failed to eliminate persistent viral forms. Therefore, new strategies to either eradicate or control these viral reservoirs are paramount to allow patients to stop antiretroviral therapy and realize a cure. Viral genome disruption based on gene editing by programmable endonucleases is one promising curative gene therapy approach...
March 9, 2018: ACS Infectious Diseases
Derek J Chan, Virginia Furner, Don E Smith, Mithilesh Dronavalli, Rohan I Bopage, Jeffrey J Post, Anjali K Bhardwaj
OBJECTIVE: To assess the prevalence of non-AIDS co-morbidities (NACs) and predictors of adverse health outcomes amongst people living with HIV in order to identify health needs and potential gaps in patient management. DESIGN: Retrospective, non-consecutive medical record audit of patients attending a publicly funded HIV clinic in metropolitan Sydney analysed for predictors of adverse health outcomes. We developed a scoring system based on the validated Charlson score method for NACs, mental health and social issues and confounders were selected using directed acyclic graph theory under the principles of causal inference...
March 8, 2018: AIDS Research and Therapy
Vinay Kumar, Joshua Mansfield, Rong Fan, Andrew MacLean, Jian Li, Mahesh Mohan
Intestinal epithelial barrier dysfunction is a well-known sequela of HIV/SIV infection that persists despite antiretroviral therapy. Although inflammation is a triggering factor, the underlying molecular mechanisms remain unknown. Emerging evidence suggests that epithelial barrier function is epigenetically regulated by inflammation-induced microRNAs (miRNAs). Accordingly, we profiled and characterized miRNA/mRNA expression exclusively in colonic epithelium and identified 46 differentially expressed miRNAs (20 upregulated and 26 downregulated) in chronically SIV-infected rhesus macaques ( Macaca mulatta )...
March 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jesús Rodríguez-Muñoz, Santiago Moreno
The disadvantages of the long-term administration of antiretroviral therapy as well as the huge number of affected persons have placed the cure of HIV as a primary goal of Public Health. HIV may persist in the organism by at least four mechanisms: a latently infected cellular reservoir, the persistent replication of HIV in spite of ART, anatomic sanctuaries, and the immune dysfunction. Several strategies directed against these mechanisms have been developed. With all this, a complete eradication of HIV has been achieved in a patient using the transplantation of haemopoietic stem cells that were resistant to HIV-infection, and there are examples of functional cure either spontaneously (elite controllers) or after antiretroviral therapy (post-treatment controllers)...
March 3, 2018: Enfermedades Infecciosas y Microbiología Clínica
Muthukumar Balasubramaniam, Jui Pandhare, Chandravanu Dash
HIV-1 has already claimed over 35 million human lives globally. No curative treatments are currently available, and the only treatment option for over 36 million people currently living with HIV/AIDS are antiretroviral drugs that disrupt the function of virus-encoded proteins. However, such virus-targeted therapeutic strategies are constrained by the ability of the virus to develop drug-resistance. Despite major advances in HIV/AIDS research over the years, substantial knowledge gaps exist in many aspects of HIV-1 replication, especially its interaction with the host...
March 3, 2018: Viruses
Narendran Gopalan, Ramesh Kumar Santhanakrishnan, Alangudi Natarajan Palaniappan, Pradeep Aravindan Menon, Sekar Lakshman, Padmapriyadarsini Chandrasekaran, Gomathi Narayan Sivaramakrishnan, Devarajulu Reddy, Bhavani Perumal Kannabiran, Hemanth Kumar Kupparam Agiboth, Vijay Krishnamoorthy, Sridhar Rathinam, Chandrasekar Chockalingam, Tamizhselvan Manoharan, MahilMaran Ayyamperumal, Nalini Jayanthi, Kumar Satagopan, Ravichandran Narayanan, Raja Krishnaraja, Sekar Sathiyavelu, Bhanu Kesavamurthy, Chandra Suresh, Murugesan Selvachitiram, Gunasundari Arasan, Stella Susaimuthu, Prabhakaran Rathinam, Prabhakar Angamuthu, Lavanya Jayabal, Lakshmi Murali, Ranjani Ramachandran, Srikanth Prasad Tripathy, Soumya Swaminathan
Importance: The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven. Objective: To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB. Design, Setting, and Participants: This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India...
March 5, 2018: JAMA Internal Medicine
S Tahseen, H Shahnawaz, U Riaz, F M Khanzada, A Hussain, W Aslam, M von Euler-Chelpin
SETTING: Pakistan is a high tuberculosis (TB) burden country, moving from low human immunodeficiency virus (HIV) prevalence to a concentrated epidemic driven primarily by people who inject drugs (PWID). The Antiretroviral Treatment Adherence Unit (AAU) in Islamabad, Pakistan, is a residential facility that offers combined treatment for opioid dependence and HIV. OBJECTIVE AND DESIGN: This retrospective study was conducted to assess TB prevalence among HIV-infected PWID referred to the AAU and to evaluate the diagnostic value of cough as a screening symptom...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
Wassim Chehadeh, Osama Albaksami, Sonia Elezebeth John, Widad Al-Nakib
OBJECTIVES: To investigate the prevalence of non-polymorphic resistance-associated mutations (RAMs) in HIV-1 patients on first-line antiretroviral therapy in Kuwait. SUBJECTS AND METHODS: Total ribonucleic acid (RNA) was isolated from plasma samples of 42 patients who received first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. HIV-1 protease and reverse transcriptase genetic regions were then amplified by nested reverse-transcription polymerase chain reaction (RT-PCR), and directly sequenced...
March 5, 2018: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
Monica B Arruda, Lídia T Boullosa, Cynthia C Cardoso, Carolina M da Costa, Carlos Rb Alves, Shirlene Ts de Lima, Helena T Kaminski, Agdemir W Aleixo, Ana Op Esposito, Ana Ms Cavalcanti, Maristela Riedel, José C Couto-Fernandez, Selma B Ferreira, Ivi Cm de Oliveira, Loreci E Portal, Hilda Hc Wolf, Sandra B Fernandes, Maria I de M C Pardini, Manoel Vc Feiteiro, Fernanda M Tolentino, Ricardo S Diaz, Giselle Isl Lopes, Roberta Bl Francisco, Nazle Mc Véras, Ana F Pires, Miriam Franchini, Fábio Mesquita, Amilcar Tanuri
INTRODUCTION: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. METHODS: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions...
March 2018: Journal of the International AIDS Society
L Ryom, C Boesecke, M Bracchi, J Ambrosioni, A Pozniak, J Arribas, G Behrens, Pgm Mallon, M Puoti, A Rauch, J M Miro, O Kirk, C Marzolini, J D Lundgren, M Battegay
BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. GUIDELINE HIGHLIGHTS: Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management...
March 1, 2018: HIV Medicine
Kazem Baesi, Marzyeh Nili, Katayoun Tayeri, Mohamad Gholami, Samaneh Moallemi, Farzaneh Sabahi, Saber Kalhori, Mehrdad Hasibi
BACKGROUND: The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. HIV-1 genome sequences are pivotal for large-scale studies of inter- and intra-host evolution. To understand the molecular difference between reference HIV-1 isolate and two HIV-1 infected patients in Iran, we conducted this study to analyze some genome segments of Iranian HIV-1 isolates. METHODS: Two HIV-1-infected individuals who were under antiretroviral therapy (ARV) for 8 years with stable clinical status were enrolled...
February 21, 2018: Infectious Disorders Drug Targets
Sanjay Pujari, Sunil Gaikwad, Vivek Bele, Kedar Joshi, Digamber Dabhade
BACKGROUND: There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. METHODS: We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history)...
January 2018: Journal of the International Association of Providers of AIDS Care
Sudeep P Pushpakom, Antonysunil Adaikalakoteswari, Andrew Owen, David J Back, Gyanendra Tripathi, Sudhesh Kumar, Philip McTernan, Munir Pirmohamed
BACKGROUND: Antiretroviral therapy in HIV-positive patients leads to insulin resistance which is central to the pathogenesis of various metabolic abnormalities and cardiovascular disease seen in this patient group. We have investigated the dose-response relationship of telmisartan, an antihypertensive, on adipocytes in vitro in order to determine whether it may have metabolic beneficial effects. METHODS: Using in vitro chronic toxicity models (3T3-F442A murine and primary human adipocytes), we evaluated the effects of different concentrations of telmisartan on adipocyte differentiation and adipogenic gene expression using lipid accumulation assays and real-time polymerase chain reaction, respectively...
February 1, 2018: Diabetes & Vascular Disease Research
Benjamin Bruno Policicchio, Paola Sette, Cuiling Xu, George Haret-Richter, Tammy Dunsmore, Ivona Pandrea, Ruy M Ribeiro, Cristian Apetrei
Two SIVmac251-infected rhesus macaques received tenofovir/emtricitabine with raltegravir intensification. Viral rebound occurred during treatment and sequencing of reverse transcriptase and integrase genes identified multiple resistance mutations. Similar to HIV infection, antiretroviral-resistance mutations may occur in SIV-infected nonhuman primates receiving nonsuppressive ART. As ART administration to nonhuman primates is currently dramatically expanding, fueled by both cure research and the study of HIV-related comorbidities, viral resistance should be factored in the study design and data interpretation...
2018: PloS One
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