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Antiretroviral resistance

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https://www.readbyqxmd.com/read/29342281/phenotypic-analysis-of-hiv-1-e157q-integrase-polymorphism-and-impact-on-virological-outcome-in-patients-initiating-an-integrase-inhibitor-based-regimen
#1
Charlotte Charpentier, Isabelle Malet, Elisabeth Andre-Garnier, Alexandre Storto, Laurence Bocket, Corinne Amiel, Laurence Morand-Joubert, Camille Tumiotto, Thuy Nguyen, Anne Maillard, Audrey Rodallec, Marie Leoz, Brigitte Montes, Véronique Schneider, Jean-Christophe Plantier, Julia Dina, Coralie Pallier, Audrey Mirand, Catherine Roussel, Anne Signori-Schmuck, Stéphanie Raymond, Vincent Calvez, Constance Delaugerre, Anne-Geneviève Marcelin, Diane Descamps
Objectives: To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen. Methods: This was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay. Results: Prevalence of the E157Q polymorphism was 2...
January 12, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29338735/mental-health-service-utilization-is-associated-with-retention-in-care-among-persons-living-with-hiv-at-a-university-affiliated-hiv-clinic
#2
Lauren A Saag, Ashutosh R Tamhane, D Scott Batey, Michael J Mugavero, Ellen F Eaton
BACKGROUND: Mental health (MH) comorbidities reduce retention in care for persons living with HIV (PLWH) and are associated with poor health outcomes. Optimizing retention in primary care is vital, as poor retention is associated with delayed receipt of antiretroviral (ARV) therapy, ARV non-adherence, and poor health outcomes, including failure to suppress viral load, decreased CD4 counts, and clinically significant ARV drug resistance. We hypothesized that MH service utilization would be associated with improved retention in care for patients with HIV and MH comorbidities...
January 16, 2018: AIDS Research and Therapy
https://www.readbyqxmd.com/read/29335428/analysis-of-the-hiv-2-protease-s-adaptation-to-various-ligands-characterization-of-backbone-asymmetry-using-a-structural-alphabet
#3
Dhoha Triki, Mario Enrique Cano Contreras, Delphine Flatters, Benoit Visseaux, Diane Descamps, Anne-Claude Camproux, Leslie Regad
The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly and binding various ligands. We propose an exhaustive study of the local structural asymmetry between the two monomers of all available PR2 structures complexed with various inhibitors using a structural alphabet approach. On average, PR2 exhibits asymmetry in 31% of its positions-i.e., exhibiting different backbone local conformations in the two monomers. This asymmetry was observed all along its structure, particularly in the elbow and flap regions...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329553/inhibitors-of-the-integrase-transportin-sr2-interaction-block-hiv-nuclear-import
#4
Jonas Demeulemeester, Jolien Blokken, Stéphanie De Houwer, Lieve Dirix, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Frauke Christ, Zeger Debyser
BACKGROUND: Combination antiretroviral therapy efficiently suppresses HIV replication in infected patients, transforming HIV/AIDS into a chronic disease. Viral resistance does develop however, especially under suboptimal treatment conditions such as poor adherence. As a consequence, continued exploration of novel targets is paramount to identify novel antivirals that do not suffer from cross-resistance with existing drugs. One new promising class of targets are HIV protein-cofactor interactions...
January 12, 2018: Retrovirology
https://www.readbyqxmd.com/read/29324842/effect-of-analytical-treatment-interruption-and-reinitiation-of-antiretroviral-therapy-on-hiv-reservoirs-and-immunologic-parameters-in-infected-individuals
#5
Katherine E Clarridge, Jana Blazkova, Kevin Einkauf, Mary Petrone, Eric W Refsland, J Shawn Justement, Victoria Shi, Erin D Huiting, Catherine A Seamon, Guinevere Q Lee, Xu G Yu, Susan Moir, Michael C Sneller, Mathias Lichterfeld, Tae-Wook Chun
Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29321330/glycosyl-phosphatidylinositol-anchored-anti-hiv-env-single-chain-variable-fragments-interfere-with-hiv-1-env-processing-and-viral-infectivity
#6
Anisha Misra, Emile Gleeson, Weiming Wang, Chaobaihui Ye, Paul Zhou, Jason T Kimata
In previous studies, we demonstrated that single-chain variable fragments (scFv) from anti-HIV Env monoclonal antibodies act as entry inhibitors when tethered to the surface of target cells by a glycosyl-phosphitidylinositol (GPI) anchor. Interestingly, even if a virus escapes inhibition at entry, its replication is ultimately controlled. We hypothesized that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also interact with Env in an infected cell, thereby interfering with infectivity of newly produced virions...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29315352/hepatitis-b-infection-among-hiv-infected-individuals-in-gabon-occult-hepatitis-b-enhances-hbv-dna-prevalence
#7
Berthold Bivigou-Mboumba, Marie Amougou-Atsama, Samira Zoa-Assoumou, Hervé M'boyis Kamdem, Guy Francis Nzengui-Nzengui, Angélique Ndojyi-Mbiguino, Richard Njouom, Sandrine François-Souquière
In Gabon, a central African country, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are endemic. In a recent study, conducted in a semi-urban area (Franceville, Gabon), HBV infection was found to be more prevalent among HIV infected individuals. This study aims to investigate the prevalence and genetic diversity of hepatitis B virus infection among HIV infected individuals, predominantly under antiretroviral therapy, living in fully urbanized area: Libreville, capital of Gabon. Serological and molecular tests were performed to detect HBV infection among patients living with HIV/AIDS (PLHA)...
2018: PloS One
https://www.readbyqxmd.com/read/29309418/emergence-as-an-outbreak-of-the-hiv-1-crf19_cpx-variant-in-treatment-na%C3%A3-ve-patients-in-southern-spain
#8
Carmen M González-Domenech, Isabel Viciana, Luis Delaye, María Luisa Mayorga, Rosario Palacios, Javier de la Torre, Francisco Jarilla, Manuel Castaño, Alfonso Del Arco, Encarnación Clavijo, Jesús Santos
BACKGROUND: CRF19_cpx is a complex circulating recombination form (CRF) of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain. METHODS: The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain). Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis...
2018: PloS One
https://www.readbyqxmd.com/read/29297444/renal-function-of-mdr-tb-patients-treated-with-kanamycin-regimens-or-concomitantly-with-antiretroviral-agents
#9
E L Sagwa, N Ruswa, F Mavhunga, T Rennie, A Mengistu, T T Mekonen, H G M Leufkens, A K Mantel-Teeuwisse
SETTING: To compare renal insufficiency among multidrug-resistant tuberculosis (MDR-TB) patients treated with kanamycin (KM) based regimens and those treated concomitantly with tenofovir disoproxil fumarate (TDF) or other antiretroviral therapy (ART) regimens in Namibia. DESIGN: Retrospective review of the treatment records and laboratory tests of patients initiated on MDR-TB treatment (January-December 2014). The glomerular filtration rates (eGFR) estimated pre- and post-treatment were compared using the analysis of variance test...
December 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29297443/screening-for-active-tuberculosis-before-isoniazid-preventive-therapy-among-hiv-infected-west-african-adults
#10
R Moh, A Badjé, J-B N'takpé, G M Kouamé, D Gabillard, T Ouassa, E Ouattara, J Le Carrou, F Bohoussou, E Messou, S Eholié, X Anglaret, C Danel
SETTING: TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance...
December 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29283390/genotypic-and-phylogenetic-insights-on-prevention-of-the-spread-of-hiv-1-and-drug-resistance-in-real-world-settings
#11
REVIEW
Bluma G Brenner, Ruxandra-Ilinca Ibanescu, Isabelle Hardy, Michel Roger
HIV continues to spread among vulnerable heterosexual (HET), Men-having-Sex with Men (MSM) and intravenous drug user (IDU) populations, influenced by a complex array of biological, behavioral and societal factors. Phylogenetics analyses of large sequence datasets from national drug resistance testing programs reveal the evolutionary interrelationships of viral strains implicated in the dynamic spread of HIV in different regional settings. Viral phylogenetics can be combined with demographic and behavioral information to gain insights on epidemiological processes shaping transmission networks at the population-level...
December 28, 2017: Viruses
https://www.readbyqxmd.com/read/29282856/chemical-composition-of-essential-oils-from-thymus-vulgaris-cymbopogon-citratus-and-rosmarinus-officinalis-and-their-effects-on-the-hiv-1-tat-protein-function
#12
Feriotto Giordana, Marchetti Nicola, Costa Valentina, Beninati Simone, Tagliati Federico, Mischiati Carlo
New drugs would be beneficial to fight resistant HIV strains, in particular those capable of interfering with essential viral functions other than those targeted by highly active antiretroviral therapy drugs. Despite the central role played by Tat protein in HIV transcription, a search for vegetable extracts able to hamper this important viral function was never carried out. In this work, we evaluated the chemical composition and possible interference of essential oil from Thymus vulgaris, Cananga odorata, Cymbopogon citratus and Rosmarinus officinalis with the Tat/TAR-RNA interaction and with Tat-induced HIV-1 LTR transcription...
December 28, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29282143/azithromycin-versus-placebo-for-the-treatment-of-hiv-associated-chronic-lung-disease-in-children-and-adolescents-breathe-trial-study-protocol-for-a-randomised-controlled-trial
#13
Carmen Gonzalez-Martinez, Katharina Kranzer, Grace McHugh, Elizabeth L Corbett, Hilda Mujuru, Mark P Nicol, Sarah Rowland-Jones, Andrea M Rehman, Tore J Gutteberg, Trond Flaegstad, Jon O Odland, Rashida A Ferrand
BACKGROUND: Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation...
December 28, 2017: Trials
https://www.readbyqxmd.com/read/29281718/the-burden-of-hepatitis-b-virus-hbv-infection-genotypes-and-drug-resistance-mutations-in-human-immunodeficiency-virus-positive-patients-in-northwest-ethiopia
#14
Tekalign Deressa, Debasu Damtie, Kevin Fonseca, Shan Gao, Ebba Abate, Shitaye Alemu, Yetemwork Aleka, Mark G Swain, Guido van Marle, Carla S Coffin
BACKGROUND: In sub-Saharan Africa, the hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are endemic. Although there has been great progress in HIV care, universal HBV vaccination and care is lacking. In this study, we aimed to determine the prevalence of HBV, HBV genotypes, and drug resistance mutations in dual infected cases in a cohort of HIV patients in Northwest Ethiopia. METHODS: A total of 308 HIV-1 positive patients were enrolled into the study and tested for HBsAg in plasma...
2017: PloS One
https://www.readbyqxmd.com/read/29279368/from-in-silico-hit-to-long-acting-late-stage-preclinical-candidate-to-combat-hiv-1-infection
#15
Shalley N Kudalkar, Jagadish Beloor, Elias Quijano, Krasimir A Spasov, Won-Gil Lee, José A Cisneros, W Mark Saltzman, Priti Kumar, William L Jorgensen, Karen S Anderson
The HIV-1 pandemic affecting over 37 million people worldwide continues, with nearly one-half of the infected population on highly active antiretroviral therapy (HAART). Major therapeutic challenges remain because of the emergence of drug-resistant HIV-1 strains, limitations because of safety and toxicity with current HIV-1 drugs, and patient compliance for lifelong, daily treatment regimens. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) that target the viral polymerase have been a key component of the current HIV-1 combination drug regimens; however, these issues hamper them...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29275329/amino-acid-residues-in-hiv-2-reverse-transcriptase-that-restrict-the-development-of-nucleoside-analogue-resistance-through-the-excision-pathway
#16
Mar Álvarez, Maria Nevot, Jesus Mendieta, Miguel A Martinez, Luis Menéndez-Arias
Nucleoside reverse transcriptase (RT) inhibitors (NRTIs) are the backbone of current antiretroviral treatments. However, emergence of viral resistance against NRTIs is a major threat to their therapeutic effectiveness. In HIV-1, NRTI resistance-associated mutations either reduce RT-mediated incorporation of NRTI triphosphates (discrimination mechanism) or confer an ATPmediated nucleotide excision activity that removes the inhibitor from the 3'-terminus of DNA primers, enabling further primer elongation (excision mechanism)...
December 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29273442/pharmaceutical-interactions-between-antiretroviral-and-antimalarial-drugs-used-in-chemoprophylaxis
#17
REVIEW
Andreas Erich Zautner, Ottmar Herchenröder, Awatef El Moussi, Norbert Georg Schwarz, Dorothea Franziska Wiemer, Uwe Groß, Hagen Frickmann
Human immunodeficiency virus (HIV) is the causative agent of the Acquired Immunodeficiency Syndrome (AIDS). The pandemic is believed to have originated within the Northern Congo basin covering large parts of the Democratic Republic of Congo, the Republic of Congo, the Central African Republic, Cameroon and Gabon. Although over decades, HIV-1 has spread throughout the World leaving no country unaffected, sub-Saharan Africa remains the region with more than 80% of all infected individuals. The HIV-2 epidemic has largely remained restricted to West Africa along the Upper Guinean forests...
December 19, 2017: Acta Tropica
https://www.readbyqxmd.com/read/29250430/divergent-hiv-1-strains-crf92_c2u-and-crf93_cpx-co-circulating-in-the-democratic-republic-of-the-congo-phylogenetic-insights-on-the-early-evolutionary-history-of-subtype-c
#18
C J Villabona Arenas, N Vidal, S Ahuka Mundeke, J Muwonga, L Serrano, J J Muyembe, F Boillot, E Delaporte, M Peeters
Molecular epidemiological studies revealed that the epicenter of the HIV pandemic was Kinshasa, the capital city of the Democratic Republic of the Congo (DRC) in Central Africa. All known subtypes and numerous complex recombinant strains co-circulate in the DRC. Moreover, high intra-subtype diversity has been also documented. During two previous surveys on HIV-1 antiretroviral drug resistance in the DRC, we identified two divergent subtype C lineages in the protease and partial reverse transcriptase gene regions...
July 2017: Virus Evolution
https://www.readbyqxmd.com/read/29250325/modern-biotechnology-based-therapeutic-approaches-against-hiv-infection
#19
Muhammad Imran, Yasir Waheed, Ayesha Ghazal, Sajjad Ullah, Sher Zaman Safi, Muhsin Jamal, Muhammad Ali, Muhammad Atif, Muhammad Imran, Farman Ullah
The causative agent of acquired immune deficiency syndrome (AIDS) is human immunodeficiency virus (HIV). Since its discovery before 30 years, a number of drugs known as highly active antiretroviral therapy have been developed to suppress the life cycle of the virus at different stages. With the current therapeutic approaches, ending AIDS means providing treatment to 35 million individuals living with HIV for the rest of their lives or until a cure is developed. Additionally, therapy is associated with various other challenges such as potential of drug resistance, toxicity and presence of latent viral reservoir...
December 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29246292/control-of-hiv-infection-in%C3%A2-vivo-using-gene-therapy-with-a-secreted-entry-inhibitor
#20
Alexander Falkenhagen, Jastaranpreet Singh, Sabah Asad, Danila Leontyev, Stanley Read, Juan Carlos Zúñiga-Pflücker, Sadhna Joshi
HIV entry inhibitors are highly effective in controlling virus replication. We have developed a lentiviral vector that expresses a secreted entry inhibitor, soluble CD4 (sCD4), which binds to the HIV envelope glycoproteins and inactivates the virus. We have shown that sCD4 was secreted from gene-modified CD4+ T cells, as well as from human umbilical cord blood-derived CD34+ hematopoietic stem/progenitor cells (HSPCs), and protected unmodified HIV target cells from infection in vitro. To investigate the in vivo application of our approach, we injected gene-modified HSPCs into NOD/SCID/γcnull (NSG) mice...
December 15, 2017: Molecular Therapy. Nucleic Acids
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