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Deniz Gokengin, Cristiana Oprea, Josip Begovac, Andrzej Horban, Arzu Nazlı Zeka, Dalibor Sedlacek, Bayjanov Allabergan, Esmira A Almamedova, Tatevik Balayan, Denes Banhegyi, Pavlina Bukovinova, Nikoloz Chkhartishvili, Alymbaeva Damira, Edona Deva, Ivaylo Elenkov, Luljeta Gashi, Dafina Gexha-Bunjaku, Vesna Hadciosmanovic, Arjan Harxhi, Tiberiu Holban, Djorje Jevtovic, David Jilich, Justyna Kowalska, Djhamal Kuvatova, Natalya Ladnaia, Adkhamjon Mamatkulov, Aleksandra Marjanovic, Maria Nikolova, Mario Poljak, Kristi Rüütel, Azzaden Shunnar, Milena Stevanovic, Zhanna Trumova, Oleg Yurin
OBJECTIVES: The aim of this survey was to describe the current status of HIV care in Central and Eastern European countries and to look at how close the region is to achieve the UNAIDS 2020 target of 90-90-90. METHODS: In 2014 data were collected from 24 Central and Eastern European countries by a 38-item questionnaire. RESULTS: All countries reported mandatory screening of blood and organ donors for HIV. Other groups who were subjected to targeted screening were people who inject drugs (PWID) (15/24; 62...
March 14, 2018: International Journal of Infectious Diseases: IJID
Dominik Brado, Adetayo Emmanuel Obasa, George Mondinde Ikomey, Ruben Cloete, Kamalendra Singh, Susan Engelbrecht, Ujjwal Neogi, Graeme Brendon Jacobs
HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatment-naive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2...
March 16, 2018: Scientific Reports
Theodoros Kelesidis, Carlee B Moser, Elizabeth Johnston, James H Stein, Michael P Dube, Otto O Yang, Grace A McComsey, Judith S Currier, Todd T Brown
BACKGROUND: The contributions of the Receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) axis to cardiovascular and bone disease in treated HIV-1 infection is not well-defined. SETTING: Prospective, observational, longitudinal study. METHODS: In a subset analysis of a prospective randomized clinical trial, 234 HIV-1-infected antiretroviral therapy (ART)-naïve participants received tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir and achieved plasma HIV-1 RNA <50 copies/ml by week 24 and thereafter...
March 12, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
David Moreno-Ajona, José Ramón Yuste, Paloma Martín, Jaime Gállego Pérez-Larraya
The human T-lymphotropic virus type 1 (HTLV-1) is a RNA retrovirus that infects a minimum of 5-10 million people worldwide. Transmission by cell-containing blood products and solid organ transplantation has been reported. Clinical disease occurs in about 5-10% of infected individuals and consists mainly in adult T cell leukemia and HTLV-1-associated myelopathy (HAM). We present a 54-year-old woman who underwent kidney transplant from cadaveric donor in March 2015. Donor also underwent cornea extraction for another recipient (corneal transplant protocol includes HTLV-1/2 serology)...
March 12, 2018: Journal of Neurovirology
Erik Mogalian, Luisa M Stamm, Anu Osinusi, Diana M Brainard, Gong Shen, Kah Hiing John Ling, Anita Mathias
Background: Combining antiviral regimens in the HCV/HIV coinfected population can be complex as they share overlapping mechanisms for elimination that may result in potential drug interactions. The pharmacokinetics, safety, and tolerability of concomitantly administered sofosbuvir/velpatasvir (SOF/VEL) with multiple commonly prescribed antiretroviral (ARV) regimens were evaluated. Methods: Healthy volunteers were enrolled into two phase 1, open-label, randomized, multiple-dose, cross-over studies...
March 7, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Antonella d'Arminio Monforte, Patrizia Lorenzini, Alessandro Cozzi-Lepri, Cristina Mussini, Antonella Castagna, Franco Baldelli, Massimo Puoti, Francesca Vichi, Adelaide Maddaloni, Sergio Lo Caputo, Nicola Gianotti, Andrea Antinori
Background We aimed to mimic the ACTG 5257 trial, comparing raltegravir (RAL), ritonavir-boosted atazavavir (ATV/r) and ritonavir-boosted darunavir (DRV/r) in the observational setting. Methods All the ICONA patients starting a first cART with 2NRTI + ATV/r, DRV/r or RAL were included. Primary end-point was treatment failure, i.e. virological failure (confirmed HIV-RNA > 200copies/mL > 6 months therapy) or discontinuation for any reason of the third drug. Secondary end-points: virological failure50 (50 copies/mL threshold), and discontinuation of the third drug due to intolerance/toxicity...
March 1, 2018: HIV Clinical Trials
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
James Demarest, Mark Underwood, Marty St Clair, David Dorey, Dannae Brown, Andrew Zolopa
Dolutegravir demonstrated superior virologic efficacy compared with raltegravir in treatment-experienced, integrase strand transfer inhibitor (INSTI)-naive patients with HIV-1 who harbored resistance to ≥2 classes of antiretroviral drugs. Significantly fewer dolutegravir-treated patients demonstrated virologic failure with treatment emergent resistance than raltegravir-treated patients through 48 weeks. Resistance analyses informed the design of investigator-selected background therapy (ISBT) that included at least 1 fully active agent...
February 14, 2018: AIDS Research and Human Retroviruses
Cleophas Chimbetete, David Katzenstein, Tinei Shamu, Adrian Spoerri, Janne Estill, Matthias Egger, Olivia Keiser
Objectives: To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe. Methods: Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program...
February 2018: Open Forum Infectious Diseases
J Nuttall, V Pillay
BACKGROUND: There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. OBJECTIVE: To describe the characteristics and early outcomes of treatment-experienced children (<20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens...
February 1, 2018: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
Harshil R Shah, Jignasa Ketan Savjani
The healthcare system faces various challenges in human immunodeficiency virus (HIV) therapy due to resistance to Anti-Retroviral Therapy (ART) as a consequence of the evolutionary process. Despite the success of antiretroviral drugs like Zidovudine, Zalcitabine, Raltegravir WHO ranks HIV as one of the deadliest diseases with a mortality of one million lives in 2016. Thus, there emerges an urgency of developing a novel anti-retroviral agent that combat resistant HIV strains. The clinical development of ART from a single drug regimen to current triple drug combination is very slow...
March 10, 2018: European Journal of Medicinal Chemistry
Katherine J Lepik, Benita Yip, Ana Ulloa, Lu Wang, Junine Toy, Linda Akagi, Viviane Dias Lima, Silvia Guillemi, Julio S G Montaner, Rolando Barrios
OBJECTIVES: Describe and compare integrase strand transfer inhibitor (INSTI) adverse drug reactions (ADRs) for raltegravir, elvitegravir-cobicistat and dolutegravir. DESIGN: Population-based, retrospective cohort. METHODS: Antiretroviral-experienced and naive persons ≥19 years were included if they received their first prescription for raltegravir, elvitegravir-cobicistat or dolutegravir in British Columbia, Canada in 2012-2014, and were followed for two years until 31-Dec-2016...
February 8, 2018: AIDS
Tomokazu Yoshinaga, Takahiro Seki, Shigeru Miki, Tadashi Miyamoto, Akemi Suyama-Kagitani, Shinobu Kawauchi-Miki, Masanori Kobayashi, Akihiko Sato, Eugene Stewart, Mark Underwood, Tamio Fujiwara
Cabotegravir (CAB, S/GSK1265744) is an investigational second-generation integrase strand transfer inhibitor (INSTI) with a chemical structure similar to dolutegravir. CAB is under development as a long-acting injectable formulation for treatment of HIV-1 infection and for pre-exposure prophylaxis. We conducted an in vitro passage study of raltegravir- or elvitegravir-resistant signature mutants in the presence of CAB to characterize the resistance profile of this drug. During passage with Q148H virus, G140S arose by day 14, followed by G149A and C56S...
January 30, 2018: Antiviral Research
Umesh Kalathiya, Monikaben Padariya, Maciej Baginski
HIV-1 integrase (IN) is crucial for integration of viral DNA into the host genome and a promising target in development of antiretroviral inhibitors. In this work, six new compounds were designed by linking the structures of two different class of HIV-1 IN inhibitors (active site binders and allosteric IN inhibitors (ALLINIs)). Among newly designed compounds, INRAT10b was found most potent HIV-1 IN inhibitor considering different docking results. To further validate protein-ligand interactions obtained from dockings, molecular dynamics simulations were performed for inhibitor raltegravir and INRAT10b placed either at active site or allosteric site of HIV-1 IN (monomer or dimer)...
February 6, 2018: Biotechnology and Applied Biochemistry
Graham P Taylor
HTLV infection appears to be more common among renal transplant candidates than in the related general population. HTLV-1-associated diseases may occur in carriers who are transplanted but there is insufficient evidence to confirm whether these occur more frequently as a result of the associated immunosuppression. Consequently, pre-existing HTLV-1 infection should not be considered a contra-indication to transplantation. The risk of transmission of HTLV-1 through solid organ transplantation from a confirmed infected donor is unknown...
January 29, 2018: Reviews in Medical Virology
Javier Martinez-Picado, Ryan Zurakowski, María José Buzón, Mario Stevenson
Reverse transcription of HIV-1 results in the generation of a linear cDNA that serves as the precursor to the integrated provirus. Other classes of extrachromosomal viral cDNA molecules can be found in acutely infected cells including the 1-LTR and 2-LTR circles of viral DNA, also referred as episomal HIV-1 DNA. Circulating CD4+ T-cells of treatment-naïve individuals contain significant levels of unintegrated forms of HIV-1 DNA. However, the importance of episomal HIV-1 DNA in the study of viral persistence during antiviral therapy (ART) is debatable...
January 30, 2018: Retrovirology
Isabelle Malet, Francesca A Ambrosio, Frédéric Subra, Béatrice Herrmann, Hervé Leh, Marie-Christine Bouger, Anna Artese, Christine Katlama, Carmine Talarico, Isabella Romeo, Stefano Alcaro, Giosuè Costa, Eric Deprez, Vincent Calvez, Anne-Geneviève Marcelin, Olivier Delelis
Background: Dolutegravir, an integrase strand-transfer inhibitor (STI), shows a high genetic barrier to resistance. Dolutegravir is reported to be effective against viruses resistant to raltegravir and elvitegravir. In this study, we report the case of a patient treated with dolutegravir monotherapy. Failure of dolutegravir treatment was observed concomitant with the appearance of N155H-K211R-E212T mutations in the integrase (IN) gene in addition to the polymorphic K156N mutation that was present at baseline in this patient...
January 24, 2018: Journal of Antimicrobial Chemotherapy
Claire Pressiat, Déborah Hirt, Jean-Marc Treluyer, Yi Zheng, Philippe Morlat, Alice Naqvi, Laurent Tran, Jean-Paul Viard, Véronique Avettand-Fenoel, Christine Rouzioux, Laurence Meyer, Antoine Cheret
Background: The OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms...
January 22, 2018: Journal of Antimicrobial Chemotherapy
Emmanuel Ndashimye, Mariano Avino, Fred Kyeyune, Immaculate Nankya, Richard M Gibson, Eva Nabulime, Art F Y Poon, Cissy Kityo, Peter Mugyenyi, Miguel E Quinones-Mateu, Eric Arts
OBJECTIVES: To screen for drug resistance and possible treatment with Dolutegravir (DTG) in treatment naïve patients and those experiencing virologic failure during first, second, and third line combined antiretroviral therapy (cART) in Uganda. DESIGN: Samples from 417 patients in Uganda were analyzed for predicted drug resistance upon failing a first (N=158), second (N=121), or third line (all 51 involving Raltegravir [RAL]) treatment regimen. METHOD: HIV-1 pol gene was amplified and sequenced from plasma samples...
January 21, 2018: AIDS Research and Human Retroviruses
Mariana Cancian, Elgion L S Loreto
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir...
January 19, 2018: Genetica
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