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https://www.readbyqxmd.com/read/28550121/bcl6-represses-antiviral-resistance-in-follicular-t-helper-cells
#1
Tohti Amet, Young Min Son, Li Jiang, In Su Cheon, Su Huang, Samir K Gupta, Alexander L Dent, Luis J Montaner, Qigui Yu, Jie Sun
Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28542550/a-spatio-temporal-assessment-of-simian-human-immunodeficiency-virus-shiv-evolution-reveals-a-highly-dynamic-process-within-the-host
#2
Alison F Feder, Christopher Kline, Patricia Polacino, Mackenzie Cottrell, Angela D M Kashuba, Brandon F Keele, Shiu-Lok Hu, Dmitri A Petrov, Pleuni S Pennings, Zandrea Ambrose
The process by which drug-resistant HIV-1 arises and spreads spatially within an infected individual is poorly understood. Studies have found variable results relating how HIV-1 in the blood differs from virus sampled in tissues, offering conflicting findings about whether HIV-1 throughout the body is homogeneously distributed. However, most of these studies sample only two compartments and few have data from multiple time points. To directly measure how drug resistance spreads within a host and to assess how spatial structure impacts its emergence, we examined serial sequences from four macaques infected with RT-SHIVmne027, a simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT), and treated with RT inhibitors...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542441/dot-or-sat-for-rifampicin-resistant-tuberculosis-a-non-randomized-comparison-in-a-high-hiv-prevalence-setting
#3
Erika Mohr, Johnny Daniels, Busisiwe Beko, Petros Isaakidis, Vivian Cox, Sarah Jane Steele, Odelia Muller, Leigh Snyman, Virginia De Azevedo, Amir Shroufi, Laura Trivino Duran, Jennifer Hughes
BACKGROUND: Daily directly-observed therapy (DOT) is recommended for rifampicin-resistant tuberculosis (RR-TB) patients throughout treatment. We assessed the impact of self-administered treatment (SAT) in a South African township with high rates of RR-TB and HIV. METHODS: Community-supported SAT for patients who completed the intensive phase was piloted in five primary care clinics in Khayelitsha. We compared final treatment outcomes among RR-TB patients initiating treatment before (standard-of-care (SOC)-cohort, January 2010-July 2013) and after the implementation of the pilot (SAT-cohort, January 2012-December 2014)...
2017: PloS One
https://www.readbyqxmd.com/read/28540766/hiv-1-full-genome-phylogenetics-of-generalized-epidemics-in-sub-saharan-africa-impact-of-missing-nucleotide-characters-in-next-generation-sequences
#4
Oliver Ratmann, Chris Wymant, Caroline Colijn, Siva Danaviah, M Essex, Simon D W Frost, Astrid Gall, Simani Gaiseitsiwe, Mary Grabowski, Ronald Gray, Stephane Guindon, Arndt von Haeseler, Pontiano Kaleebu, Michelle Kendall, Alexey Kozlov, Justen Manasa, Bui Quang Minh, Sikhulile Moyo, Vladimir Novitsky, Rebecca Nsubuga, Sureshnee Pillay, Thomas C Quinn, David Serwadda, Deogratius Ssemwanga, Alexandros Stamatakis, Jana Trifinopoulos, Maria Wawer, Andrew Leigh Brown, Tulio de Oliveira, Paul Kellam, Deenan Pillay, Christophe Fraser
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28539977/human-immunodeficiency-virus-and-type-2-diabetes
#5
P Avari, S Devendra
The prevalence of diabetes is higher amongst individuals infected with HIV. The major contributor to hyperglycaemia is thought to be iatrogenic, with protease inhibitors being most commonly associated to insulin resistance. This article is to update general practitioners on the diagnosis and management of diabetes in HIV-infected patients. Specific considerations are highlighted including interactions of particular diabetic drugs with antiretroviral therapy (ART). We articulate why the use of Hemoglobin A1c (HbA1c) testing is not recommended as a diagnostic tool...
May 2017: London Journal of Primary Care
https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#6
Rajesh P Ringe, Gabriel Ozorowski, Kimmo Rantalainen, Weston B Struwe, Katie Matthews, Jonathan L Torres, Anila Yasmeen, Christopher A Cottrell, Thomas J Ketas, Celia C LaBranche, David C Montefiori, Albert Cupo, Max Crispin, Ian A Wilson, Andrew B Ward, Rogier W Sanders, P J Klasse, John P Moore
Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs), but can also expose binding sites for some types of non-neutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such "off-target" immune responses...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539254/prevalence-of-primary-resistance-among-acutely-recently-hiv-infected-patients-in-rio-de-janeiro-brazil
#7
Ana Cristina G Ferreira, Lara E Coelho, Eduarda Grinsztejn, Carlos S de Jesus, Monick L Guimarães, Valdilea G Veloso, Beatriz Grinsztejn, Sandra W Cardoso
INTRODUCTION: The widespread use of antiretroviral therapy (ART) increased the transmission of antiretroviral resistant HIV strains. ART initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance (TDR) may jeopardize the early goals of early ART among acute/recent HIV infected patients. METHODS: Patients with acute/recent HIV infection who underwent resistance test before ART initiation were included in this analysis...
May 21, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28537061/dolutegravir-lamivudine-as-initial-therapy-in-hiv-1-infected-arv-naive-patients-48-week-results-of-the-paddle-pilot-antiretroviral-design-with-dolutegravir-lamivudine-study
#8
Pedro Cahn, María José Rolón, María Inés Figueroa, Ana Gun, Patricia Patterson, Omar Sued
INTRODUCTION: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. METHODS: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg...
May 9, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28534892/minimizing-next-generation-sequencing-errors-for-hiv-drug-resistance-testing
#9
José A Fernández-Caballero, Natalia Chueca, Eva Poveda, Federico García
Next-generation sequencing prototypes for the routine diagnosis of resistance to antiretrovirals approved for the treatment of HIV infection are now being used in many clinical diagnostic laboratories. As some of the next-generation sequencing platforms may be a source of errors, it is necessary to improve the currently available protocols and implement bioinformatic tools that may help to correctly identify the presence of resistance mutations with clinical impact. Several studies have addressed these issues in recent years...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28534889/hiv-1-infection-in-persons-homozygous-for-ccr5-%C3%AE-32-allele-the-next-case-and-the-review
#10
Joanna Smoleń-Dzirba, Magdalena Rosińska, Janusz Janiec, Marek Beniowski, Mariusz Cycoń, Jolanta Bratosiewicz-Wąsik, Tomasz J Wąsik
CC-chemokine receptor 5 serves as the coreceptor for the HIV-1 R5 strains, which are responsible for the majority of HIV transmissions. A deletion of 32 nucleotides in the gene encoding this receptor (termed CCR5-Δ32) leads to the suppression of CC-chemokine receptor 5 presentation at the cell surface, thus impeding process of HIV entry into the cell. Individuals homozygous for the CCR5-Δ32 allele are resistant to infection with HIV-1 R5 strains, and are extremely rare among HIV-1-infected individuals. We have described a case of person homozygous for CCR5-Δ32, who was infected with subtype B HIV-1...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28534886/a-new-hiv-paradigm-dual-antiretroviral-regimens-as-maintenance-therapy
#11
Vicente Soriano, José M Peña
Since the advent of triple combination antiretroviral therapy in 1996, the prognosis of HIV-infected persons has improved drastically. The clinical benefits of HAART derive from producing sustained viral load suppression and CD4 gains. The major drawbacks of the first HAART regimens were common adverse events and high pill burden, which resulted in difficult drug adherence and led to frequent discontinuations and selection of drug resistance.
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28533248/impact-of-hiv-1-integrase-l74f-v75i-mutations-from-a-clinical-isolate-on-resistance-to-second-generation-integrase-strand-transfer-inhibitors
#12
Atsuko Hachiya, Karen A Kirby, Yoko Ido, Urara Shigemi, Masakazu Matsuda, Reiko Okazaki, Junji Imamura, Stefan G Sarafianos, Yoshiyuki Yokomaku, Yasumasa Iwatani
A novel HIV-1 integrase mutation pattern, L74F/V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F/V75I to N155H or G140S/Q148H increased resistance levels to second-generation INSTIs, dolutegravir (>385-, 100-fold, respectively) and cabotegravir (153-, 197-fold, respectively). These findings are important for developing an accurate interpretation system of INSTI resistance and the rational design of next-generation INSTIs...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28532715/caretakers-barriers-to-pediatric-antiretroviral-therapy-adherence-in-vietnam-a-qualitative-and-quantitative-study
#13
C T Tran, T H Pham, K T Tran, T K C Nguyen, M Larsson
BACKGROUND: Poor antiretroviral therapy (ART) adherence leads to drug resistance and treatment failures. The options for second and third line ART regimens, particularly for pediatric patients, are very limited in low and middle-income countries. HIV-infected children are mostly passive drug-takers, thus caretakers play a very important role in assuring ART adherence. Pediatric ART adherence is still a challenging problem in Vietnam since non-adherence is the major risk factor for treatment failure...
June 2017: Applied Nursing Research: ANR
https://www.readbyqxmd.com/read/28532596/costs-and-cost-efficacy-analysis-of-the-2017-gesida-spanish-national-aids-plan-recommended-guidelines-for-initial-antiretroviral-therapy-in-hiv-infected-adults
#14
Antonio Rivero, José Antonio Pérez-Molina, Antonio Javier Blasco, José Ramón Arribas, Víctor Asensi, Manuel Crespo, Pere Domingo, José Antonio Iribarren, Pablo Lázaro, José López-Aldeguer, Fernando Lozano, Esteban Martínez, Santiago Moreno, Rosario Palacios, Juan Antonio Pineda, Federico Pulido, Rafael Rubio, Jesús Santos, Javier de la Torre, Montserrat Tuset, Josep M Gatell
INTRODUCTION: GESIDA and the Spanish National AIDS Plan panel of experts have recommended preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral therapy (ART) as initial therapy in HIV-infected patients for 2017. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. METHODS: Economic assessment of costs and efficiency (cost-efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis...
May 19, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28529205/effectiveness-and-safety-of-bedaquiline-containing-regimens-in-the-treatment-of-mdr-and-xdr-tb-a-multicentre-study
#15
Sergey E Borisov, Keertan Dheda, Martin Enwerem, Rodolfo Romero Leyet, Lia D'Ambrosio, Rosella Centis, Giovanni Sotgiu, Simon Tiberi, Jan-Willem Alffenaar, Andrey Maryandyshev, Evgeny Belilovski, Shashank Ganatra, Alena Skrahina, Onno Akkerman, Alena Aleksa, Rohit Amale, Janina Artsukevich, Judith Bruchfeld, Jose A Caminero, Isabel Carpena Martinez, Luigi Codecasa, Margareth Dalcolmo, Justin Denholm, Paul Douglas, Raquel Duarte, Aliasgar Esmail, Mohammed Fadul, Alexey Filippov, Lina Davies Forsman, Mina Gaga, Julia-Amaranta Garcia-Fuertes, José-María García-García, Gina Gualano, Jerker Jonsson, Heinke Kunst, Jillian S Lau, Barbara Lazaro Mastrapa, Jorge Lazaro Teran Troya, Selene Manga, Katerina Manika, Pablo González Montaner, Jai Mullerpattan, Suzette Oelofse, Martina Ortelli, Domingo Juan Palmero, Fabrizio Palmieri, Antonella Papalia, Apostolos Papavasileiou, Marie-Christine Payen, Emanuele Pontali, Carlos Robalo Cordeiro, Laura Saderi, Tsetan Dorji Sadutshang, Tatsiana Sanukevich, Varvara Solodovnikova, Antonio Spanevello, Sonam Topgyal, Federica Toscanini, Adrian R Tramontana, Zarir Farokh Udwadia, Pietro Viggiani, Veronica White, Alimuddin Zumla, Giovanni Battista Migliori
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28527722/crispr-cas9-mediated-ccr5-ablation-in-human-hematopoietic-stem-progenitor-cells-confers-hiv-1-resistance-in%C3%A2-vivo
#16
Lei Xu, Huan Yang, Yang Gao, Zeyu Chen, Liangfu Xie, Yulin Liu, Ying Liu, Xiaobao Wang, Hanwei Li, Weifeng Lai, Yuan He, Anzhi Yao, Liying Ma, Yiming Shao, Bin Zhang, Chengyan Wang, Hu Chen, Hongkui Deng
Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4(+) T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34(+) HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdc(scid)/IL-2Rγ(null) mice...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28527291/haplotypes-in-ccr5-ccr2-ccl3-and-ccl5-are-associated-with-natural-resistance-to-hiv-1-infection-in-a-colombian-cohort
#17
Jorge A Vega, Simón Villegas-Ospina, Wbeimar Aguilar-Jiménez, María T Rugeles, Gabriel Bedoya, Wildeman Zapata
INTRODUCTION: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. OBJECTIVE: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. MATERIALS AND METHODS: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls)...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527252/-characterization-of-clinical-isolates-of-mycobacterium-tuberculosis-from-hiv-positive-individuals-in-colombia-2012
#18
Claudia Castro, Alba Ricardo, Angie Zabaleta, Claudia Llerena, Gloria Puerto
INTRODUCTION: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. OBJECTIVE: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28521719/virological-suppression-and-patterns-of-resistance-amongst-patients-on-antiretroviral-therapy-at-4-nigerian-military-hospitals
#19
Keshinro Babajide, Ayemoba Ojor, Terfa Kene, Ake Julie, Crowell Trevor A, Adamu Yakubu, Mohammed Tahir, Okoye Ifeanyi, Odeyemi Sunday, Crawford Keith, Hughes Lindsay, Akintunde Ezekiel, Umar Tahir, Hamm Tiffany E, Njoku Ogbonnaya S
BACKGROUND: In resource-constrained settings, plasma HIV-1 RNA quantification has not been routinely available for the monitoring of response to antiretroviral therapy. This study evaluated virological suppression rates amongst patients on first-line ART in four Nigerian military hospitals. METHODS: We conducted a cross-sectional study of 325 randomly selected adult clinic clients (≥18 years old) on first-line ART regimens at four Nigerian military hospitals. Plasma HIV-1 RNA was assayed using a Roche COBAS TaqMan48 with High Pure System...
May 16, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28520611/treatment-outcomes-of-third-line-antiretroviral-regimens-in-hiv-infected-thai-adolescents
#20
Wasana Prasitsuebsai, Jiratchaya Sophonphan, Kulkanya Chokephaibulkit, Jurai Wongsawat, Suparat Kanjanavanit, Pope Kosalaraksa, Chaiwat Ngampiyakul, Pakarat Sangkla, Rawiwan Hansudewechakul, Stephen J Kerr, Thanyawee Puthanakit, Jintanat Ananworanich
BACKGROUND: Efficacy and safety data of third-line antiretroviral (ARV) regimens in adolescents are limited. METHODOLOGY: This study enrolled HIV-infected Thais who were treated with third-line regimens consisting of darunavir/ritonavir (DRV/r), etravirine (ETR), tipranavir/ritonavir (TPV/r) or raltegravir (RAL). RESULTS: Fifty-four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48 weeks. Reasons for switch were second-line failure (n=44) and toxicity to second-line regimens (n=10)...
May 16, 2017: Pediatric Infectious Disease Journal
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