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https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#1
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28816644/cyp2b6-haplotype-predicts-efavirenz-plasma-concentration-in-black-south-african-hiv-1-infected-children-a-longitudinal-pediatric-pharmacogenomic-study
#2
Riaan Reay, Collet Dandara, Michelle Viljoen, Malie Rheeders
South Africa has the highest burden of the human immunodeficiency virus (HIV) infection globally. Efavirenz (EFV), a frequently used drug against HIV infection, displays a relationship between drug concentration and pharmacodynamics effects clinically. However, haplotype-based genetic variation in drug metabolism in a pediatric sample has been little considered in a longitudinal long-term context. CYP2B6 plays a key role in variation of EFV plasma concentration through altered drug metabolism. We report here on a prospective clinical pharmacogenomics/pharmacokinetic study of Bantu-speaking children, importantly, over a period of 24 months post-initiation of EFV-based treatment in South Africa...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28814161/significant-rates-of-risky-sexual-behaviours-among-hiv-infected-patients-failing-first-line-art-a-sub-study-of-the-europe-africa-research-network-for-the-evaluation-of-second-line-therapy-trial
#3
Jane N Wanyama, Maria S Nabaggala, Bonnie Wandera, Agnes N Kiragga, Barbara Castelnuovo, Ivan K Mambule, Josephine Nakajubi, Andrew D Kambugu, Nicholas I Paton, Rhoda K Wanyenze, Robert Colebunders, Philippa Easterbrook
There are limited data on the prevalence of risky sexual behaviours in individuals failing first-line antiretroviral therapy (ART) and changes in sexual behaviour after switch to second-line ART. We undertook a sexual behaviour sub-study of Ugandan adults enrolled in the Europe-Africa Research Network for the Evaluation of Second-line Therapy trial. A standardized questionnaire was used to collect sexual behaviour data and, in particular, risky sexual behaviours (defined as additional sexual partners to main sexual partner, inconsistent use of condoms, non-disclosure to sexual partners, and exchange of money for sex)...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28811600/exploring-leishmania-secretory-proteins-to-design-b-and-t-cell-multi-epitope-subunit-vaccine-using-immunoinformatics-approach
#4
Nazia Khatoon, Rajan Kumar Pandey, Vijay Kumar Prajapati
Visceral leishmaniasis (VL) is a fatal form of leishmaniasis which affects 70 countries, worldwide. Increasing drug resistance, HIV co-infection, and poor health system require operative vaccination strategy to control the VL transmission dynamics. Therefore, a holistic approach is needed to generate T and B memory cells to mediate long-term immunity against VL infection. Consequently, immunoinformatics approach was applied to design Leishmania secretory protein based multi-epitope subunit vaccine construct consisting of B and T cell epitopes...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810826/improving-fold-resistance-prediction-of-hiv-1-against-protease-and-reverse-transcriptase-inhibitors-using-artificial-neural-networks
#5
Olivier Sheik Amamuddy, Nigel T Bishop, Özlem Tastan Bishop
BACKGROUND: Drug resistance in HIV treatment is still a worldwide problem. Predicting resistance to antiretrovirals (ARVs) before starting any treatment is important. Prediction accuracy is essential, as low-accuracy predictions increase the risk of prescribing sub-optimal drug regimens leading to patients developing resistance sooner. Artificial Neural Networks (ANNs) are a powerful tool that would be able to assist in drug resistance prediction. In this study, we constrained the dataset to subtype B, sacrificing generalizability for a higher predictive performance, and demonstrated that the predictive quality of the ANN regression models have definite improvement for most ARVs...
August 15, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28807730/development-of-a-dual-reporter-screening-assay-for-distinguishing-the-inhibition-of-hiv-tat-mediated-transcription-from-off-target-effects
#6
YoungHyun Shin, Byeong-Sun Choi, Kyung-Chang Kim, Chun Kang, Kisoon Kim, Cheol-Hee Yoon
Human immunodeficiency virus (HIV) encodes a transcription trans-activator (Tat) with an essential role in the transcriptional elongation of viral RNA based on the viral promoter long terminal repeat (LTR). Tat-mediated transcription is conserved and can be distinguished from host transcription, so it is a therapeutic target for combating HIV replication. Traditional screening assays for Tat-mediated transcriptional inhibitors are based on the biochemical properties of Tat and transactivation-responsive RNA...
August 11, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28799325/comparison-between-next-generation-and-sanger-based-sequencing-for-the-detection-of-transmitted-drug-resistance-mutations-among-recently-infected-hiv-1-patients-in-israel-2000-2014
#7
Roy Moscona, Daniela Ram, Marina Wax, Efrat Bucris, Itzchak Levy, Ella Mendelson, Orna Mor
INTRODUCTION: Transmitted drug-resistance mutations (TDRM) may hamper successful anti-HIV-1 therapy and impact future control of the HIV-1 epidemic. Recently infected, therapy-naïve individuals are best suited for surveillance of such TDRM. In this study, TDRM, detected by next-generation sequencing (NGS) were compared to those identified by Sanger-based population sequencing (SBS) in recently infected HIV-1 patients. METHODS: Historical samples from 80 recently infected HIV-1 patients, diagnosed between 2000 and 2014, were analysed by MiSeq (NGS) and ABI (SBS)...
August 11, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28797860/palliative-care-for-tuberculosis
#8
Stephen R Connor
In 2014, 1.5 million people died of tuberculosis (TB) worldwide including 400,000 co-infected with HIV. TB remains a major cause of death and suffering globally, in spite of the fact that it is supposed to be a curable disease. Drug resistant forms of TB have developed as a result of poor treatment compliance including multi-drug and extreme drug resistant forms that take longer to treat and have higher likelihoods of treatment failure. In 2010, at the initiation of the TB community, a partnership was formed between the WHO Stop TB Program, the Worldwide Hospice Palliative Care Alliance, and the Open Society Foundation's International Palliative Care Initiative (OSF/IPCI) to explore how to improve the ability of TB professionals to deliver palliative care to their patients...
August 7, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28795954/the-first-characterization-of-hiv-1-subtypes-and-drug-resistance-mutations-among-antiretrovirally-treated-patients-in-kermanshah-iran
#9
Reza Golmohammadi, Kazem Baesi, Abdolvahab Moradi, Molood Farrokhi, Willi McFarland, Shahryar Parsamajd
BACKGROUND: Insufficient therapy during HIV-1 replication can promote the emergence of drug-resistant strains, reduce the effectiveness of antiretroviral treatment (ART), and increase the likelihood of the onward transmission of drug-resistant viruses. We characterized, for the first time, the prevalence of HIV-1 subtypes and drug resistance mutations in a western region of Iran. METHODS: This study was conducted among 122 patients on ART at a major referral center in Kermanshah, Iran...
August 10, 2017: Intervirology
https://www.readbyqxmd.com/read/28795354/drug-resistance-mutation-profiles-of-the-drug-na%C3%A3-ve-and-first-line-regimen-treated-hiv-1-infected-population-of-suzhou-china
#10
Tingting Li, Feng Qian, Ting Yuan, Weilu Xu, Li Zhu, Jinlong Huang, Haiyan Wang, Yueping Zhu, Yinling Wang, Xiaohong Li, Saihong Gu, Zhuqing Tan, Hui Chen, Xiangrong Luo, Wei Zhu, Wenjuan Lu, Ping Xu, Ming Li, Yuying Chen, Yong Gao, Rongge Yang, Chuanwu Zhu, Binlian Sun
Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles, we collected blood specimens from 127 drug-naïve and 117 first-line drug-treated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples. We then determined the drug-resistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database...
August 7, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28794047/no-substantial-evidence-for-sexual-transmission-of-minority-hiv-drug-resistance-mutations-in-men-who-have-sex-with-men
#11
Antoine Chaillon, Masato Nakazawa, Joel O Wertheim, Susan J Little, Davey M Smith, Sanjay R Mehta, Sara Gianella
During primary HIV-infection, the presence of minority drug resistant mutations (DRM) may be a consequence of sexual transmission, de novo mutations or technical errors. Baseline blood samples were collected from 24 HIV-infected antiretroviral-naive, genetically- and epidemiologically- linked source and recipient partners, shortly after the recipient's estimated date of infection. An additional 32 longitudinal samples were available from 11 recipients. Deep-sequencing of HIV reverse transcriptase (RT) was performed (Roche/454) and screened for nucleoside and non-nucleoside RT inhibitor DRM...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28793873/epidemiological-trends-and-outcomes-of-extensively-drug-resistant-tuberculosis-in-shandong-china
#12
Xiao-Chun He, Ning-Ning Tao, Yao Liu, Xian-Xin Zhang, Huai-Chen Li
BACKGROUND: Extensively Drug-Resistant (XDR) Tuberculosis (TB) has posed a great threat to global health and finance systems, especially for developing countries with high TB and Multidrug-Resistant (MDR) TB burden. METHODS: We retrospectively analyzed HIV-uninfected TB case confirmed and treated in Shandong Provincial Chest Hospital (SPCH) between January 2008 and December 2015. Unique characteristics of XDR-TB were identified; its longitudinal changes and survival were analyzed...
August 9, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28793019/cryptococcus-neoformans-and-c-gattii-isolates-from-both-hiv-infected-and-uninfected-patients-antifungal-susceptibility-and-outcome-of-cryptococcal-disease
#13
Erika Nascimento, Lucia Helena Vitali, Marcia Regina von Zeska Kress, Roberto Martinez
One of the factors causing treatment failure in cryptococcosis is the resistance of Cryptococcus spp. to antifungal drugs, which has motivated the susceptibility assessment of isolates from patients with cryptococcosis, different clinical conditions and infections outcomes. Clinical isolates of Cryptococcus spp. from three different groups of patients were studied in the present investigation: 19 HIV-positive patients with relapsing and/or refractory meningitis (Group 1), 30 HIV-positive patients who experienced a single and limited episode of cryptococcosis (Group 2), and 19 HIV-negative patients with cryptococcosis (Group 3)...
2017: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/28791894/decoding-hiv-resistance-from-genotype-to-therapy
#14
Irene T Weber, Robert W Harrison
Genetic variation in HIV poses a major challenge for prevention and treatment of the AIDS pandemic. Resistance occurs by mutations in the target proteins that lower affinity for the drug or alter the protein dynamics, thereby enabling viral replication in the presence of the drug. Due to the prevalence of drug-resistant strains, monitoring the genotype of the infecting virus is recommended. Computational approaches for predicting resistance from genotype data and guiding therapy are discussed. Many prediction methods rely on rules derived from known resistance-associated mutations, however, statistical or machine learning can improve the classification accuracy and assess unknown mutations...
August 9, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28791686/the-role-of-dna-polymerase-chain-reaction-culture-and-histopathology-in-the-diagnosis-of-cutaneous-tuberculosis
#15
Puneet Agarwal, Elangbam Nelson Singh, Uma Shankar Agarwal, Ramsingh Meena, Saroj Purohit, Surendra Kumar
BACKGROUND: Cutaneous tuberculosis (TB) is re-emerging as a significant problem in India due to increased incidence of human immunodeficiency virus (HIV), acquired immune deficiency syndrome (AIDS), other immunosuppressive states/factors like drugs, and emergence of multidrug resistance (MDR-TB). Proper diagnosis is warranted as there is varied clinical presentation and similarity with many other diseases. OBJECTIVE: To assess the sensitivities of DNA polymerase chain reaction (PCR), culture, and histopathology for the diagnosis of cutaneous TB in clinically suspected skin lesions...
August 9, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28782605/drug-adherence-and-efficacy-of-smear-microscopy-in-the-diagnosis-of-pulmonary-tuberculosis-after-2-months-of-medication-in-north-western-tanzania
#16
Benson R Kidenya, Stephen E Mshana, Lisa Gerwing-Adima, Jeremiah Kidola, Christa Kasang
OBJECTIVES: The study aimed at assessing the Tuberculosis (TB) medication adherence level and the efficacy of smear microscopy in the diagnosing pulmonary TB at month 2. METHODS: A prospective study was conducted at the four sites located in the Northern-western Tanzania. New smear positive, pulmonary TB patients were followed up and their adherence to TB medication assessed after 2 months of the treatment. In addition, the acid fast bacilli (AFB) smear microscopy was performed after 2 and 5 months of the treatment...
August 3, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28774702/candida-and-invasive-mould-diseases-in-non-neutropenic-critically-ill-patients-and-patients-with-haematological-cancer
#17
REVIEW
A L Colombo, J N de Almeida Júnior, Monica A Slavin, Sharon C-A Chen, Tania C Sorrell
Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches...
July 31, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28774701/fungal-infections-in-hiv-aids
#18
REVIEW
Andrew H Limper, Antoine Adenis, Thuy Le, Thomas S Harrison
Fungi are major contributors to the opportunistic infections that affect patients with HIV/AIDS. Systemic infections are mainly with Pneumocystis jirovecii (pneumocystosis), Cryptococcus neoformans (cryptococcosis), Histoplasma capsulatum (histoplasmosis), and Talaromyces (Penicillium) marneffei (talaromycosis). The incidence of systemic fungal infections has decreased in people with HIV in high-income countries because of the widespread availability of antiretroviral drugs and early testing for HIV. However, in many areas with high HIV prevalence, patients present to care with advanced HIV infection and with a low CD4 cell count or re-present with persistent low CD4 cell counts because of poor adherence, resistance to antiretroviral drugs, or both...
July 31, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28774413/management-of-hepatitis-b-in-special-populations
#19
REVIEW
Kali Zhou, Norah Terrault
Special populations infected with chronic HBV include those with decompensated cirrhosis, coinfections (HIV, HCV, HDV), hemodialysis and renal failure, immunosuppressed including transplant patients, children and women in pregnancy. These populations differ in their natural history and risk for liver-related complications, the indications for anti-HBV therapy as well as the recommendations regarding the HBV drugs used, duration of therapy and anticipated endpoints. Reflecting the special populations with substantive changes in management in recent years, this review focuses on HBV-HIV coinfected patients, immunosuppressed patients at risk for reactivation, liver transplant recipients and pregnant women...
June 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28770939/chemical-optimization-of-macrocyclic-hiv-1-inactivators-for-improving-potency-and-increasing-the-structural-diversity-at-the-triazole-ring
#20
Adel A Rashad, Kriti Acharya, Ann Haftl, Rachna Aneja, Alexej Dick, Andrew P Holmes, Irwin Chaiken
HIV-1 entry inhibition remains an urgent need for AIDS drug discovery and development. We previously reported the discovery of cyclic peptide triazoles (cPTs) that retain the HIV-1 irreversible inactivation functions of the parent linear peptides (PTs) and have massively increased proteolytic resistance. Here, in an initial structure-activity relationship investigation, we evaluated the effects of variations in key structural and functional components of the cPT scaffold in order to produce a platform for developing next-generation cPTs...
August 3, 2017: Organic & Biomolecular Chemistry
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