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https://www.readbyqxmd.com/read/29782334/inhibitors-of-the-hiv-1-capsid-a-target-of-opportunity
#1
Stephanie K Carnes, Jonathan H Sheehan, Christopher Aiken
PURPOSE OF REVIEW: To summarize recent advances in the discovery of chemical inhibitors targeting the HIV capsid and research on their mechanisms of action. RECENT FINDINGS: HIV infection is critically dependent on functions of the viral capsid. Numerous studies have reported the identification of a variety of compounds that bind to the capsid protein; some of these inhibit reverse transcription and nuclear entry, steps required for infection. Other capsid-targeting compounds appear to act by perturbing capsid assembly, resulting in noninfectious progeny virions...
May 18, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29781356/combating-the-hiv-reservoirs
#2
Guido van Marle, Deirdre L Church, Frank van der Meer, M John Gill
Impressive advances have been made in the treatment and management of HIV-1 infected individuals. Combination antiretroviral therapy (cART) has turned HIV-1 infection from an almost invariable deadly infectious disease, to a lifelong manageable infectious disease. However, a cure or vaccine has not been forthcoming. A major problem in HIV-1 infection is the persistent and latently infected cellular and tissue reservoirs. One of these reservoirs is the Gut Associated Lymphoid tissue (GALT), which has been the research focus of our group...
May 21, 2018: Biotechnology & Genetic Engineering Reviews
https://www.readbyqxmd.com/read/29778137/deciphering-natural-control-of-hiv-1-a-valuable-strategy-to-achieve-antiretroviral-therapy-termination
#3
REVIEW
Hamza Loucif, Steven Gouard, Xavier Dagenais-Lussier, Armstrong Murira, Simona Stäger, Cécile Tremblay, Julien Van Grevenynghe
Antiretroviral therapy (ART) has dramatically reduced HIV-1-associated morbidity and mortality, and has transformed HIV-1 infection into a manageable chronic condition by suppressing viral replication. However, despite recent patient care improvements, ART still fails to cure HIV-1 infection due to the inability to counteract immune defects and metabolic disturbances that are associated with residual inflammation alongside viral persistence. Life-long drug administration also results in multiple side-effects in patients including lipodystrophy and insulin resistance...
April 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29771783/hiv-1-drug-resistance-among-ugandan-adults-attending-an-urban-out-patient-clinic
#4
Amrei von Braun, Christine Sekaggya-Wiltshire, Nadine Bachmann, Deogratius Ssemwanga, Alexandra U Scherrer, Maria Nanyonjo, Anne Kapaata, Pontiano Kaleebu, Huldrych F Günthard, Barbara Castelnuovo, Jan Fehr, Andrew Kambugu
BACKGROUND: Little is known about prevalence of drug resistance among HIV-infected Ugandans, a setting with over 15 years of public-sector access to antiretroviral therapy (ART) and where virological monitoring was only recently introduced. SETTING: This study was conducted in the adults' out-patient clinic of the Infectious Diseases Institute, Kampala, Uganda. METHODS: HIV genotyping was performed in ART naïve patients and in treatment experienced patients on ART for ≥ six months with virological failure (≥1000 copies/mL)...
April 27, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29771694/fostemsavir-a-new-cd4-attachment-inhibitor
#5
Pedro Cahn, Valeria Fink, Patricia Patterson
PURPOSE OF REVIEW: Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium. RECENT FINDINGS: Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds...
May 15, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29769116/efficacies-of-cabotegravir-and-bictegravir-against-drug-resistant-hiv-1-integrase-mutants
#6
Steven J Smith, Xue Zhi Zhao, Terrence R Burke, Stephen H Hughes
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. However, recent studies showed that when INSTI-experienced patients are put on a DTG-salvage therapy, they have reduced response rates...
May 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29767543/efficacy-of-single-tablet-darunavir-cobicistat-emtricitabine-and-tenofovir-alafenamide-in-the-treatment-of-hiv-1
#7
Eugènia Negredo, Bonaventura Clotet
HIV eradication is not feasible and lifelong treatment is warranted to manage HIV infection. In this scenario, the advent of single-tablet, once-daily, fixed-dose co-formulations is important for reducing pill burden and maximize long-term drug adherence. Cobicistat-boosted darunavir along with emtricitabine and tenofovir alafenamide co-formulation (DRV/c/FTC/TAF or the trade name Symtuza®) is the first marketed protease inhibitor-based fixed-dose combination regimen for the treatment of HIV infection. It was approved in late 2017 by the European Medical Agency both for naïve patients and treatment-experienced patients with viral suppression...
May 16, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29766800/antifungal-activity-gas-chromatographic-mass-spectrometric-analysis-and-in-silico-study-of-punica-granatum-peel-extracts-against-fluconazole-resistant-strains-of-candida-species
#8
Sony Paul, M Kalyani, I Kannan
AIMS: Candida species is the common cause of opportunistic fungal infections all over the world with increased mortality and morbidity especially in immunosuppressed patients. Fluconazole is the first line therapy for candidiasis. The antifungal resistance pattern in high-risk patients is a major concern. The present study was aimed to assess the anticandidal activity of Punica granatum peel against fluconazole resistant Candida species isolated from HIV patients. MATERIALS & METHODS: Ethanol, chloroform, petroleum ether and aqueous extracts of the peel of P...
May 14, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29765082/pretreatment-drug-resistance-in-a-large-countrywide-ethiopian-hiv-1c-cohort-a-comparison-of-sanger-and-high-throughput-sequencing
#9
Nigus Fikrie Telele, Amare Worku Kalu, Solomon Gebre-Selassie, Daniel Fekade, Samir Abdurahman, Gaetano Marrone, Ujjwal Neogi, Belete Tegbaru, Anders Sönnerborg
Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also next generation sequencing (NGS) was used in a subset of 109 baseline samples of patients. Treatment outcome after 6- and 12-months was assessed by on-treatment (OT) and intention-to-treat (ITT) analyses. Transmitted drug resistance (TDR) was detected in 3...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29757986/medicinal-plants-used-in-the-treatment-of-human-immunodeficiency-virus
#10
REVIEW
Bahare Salehi, Nanjangud V Anil Kumar, Bilge Şener, Mehdi Sharifi-Rad, Mehtap Kılıç, Gail B Mahady, Sanja Vlaisavljevic, Marcello Iriti, Farzad Kobarfard, William N Setzer, Seyed Abdulmajid Ayatollahi, Athar Ata, Javad Sharifi-Rad
Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29756454/discordance-in-drug-resistance-mutations-between-blood-plasma-and-semen-or-rectal-secretion-among-newly-diagnosed-hiv-1-infected-thai-msm
#11
Akarin Hiransuthikul, Rapeeporn Wongkanya, Sunee Sirivichayakul, Deondara Trachunthong, Thanthip Sungsing, Tippawan Pankam, Praphan Phanuphak, Nittaya Phanuphak
HIV-1 infection is most commonly transmitted by sexual contact across mucosal surfaces. Information on concordance in drug resistance profile between blood plasma and anogenital compartments in resource-limited settings is limited. We aimed to determine discordances in genotypic drug resistance-associated mutations (DRAMs) between blood plasma and semen or rectal secretions among newly diagnosed, antiretroviral therapy (ART)-naïve, HIV-1-infected Thai men who have sex with men (MSM). Blood plasma, semen, and rectal secretions of HIV-1-infected Thai MSM enrolled from the Test and Treat cohort were tested for genotypic mutations in the reverse transcriptase and protease genes...
May 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29753024/chemical-system-biology-based-molecular-interactions-to-identify-inhibitors-against-q151m-mutant-of-hiv-1-reverse-transcriptase
#12
Rajan Kumar Pandey, Drista Sharma, Rupal Ojha, Tarun Kumar Bhatt, Vijay Kumar Prajapati
The emergence of mutations leading to drug resistance is the main cause of therapeutic failure in the human HIV infection. Chemical system biology approach has drawn great attention to discover new antiretroviral hits with high efficacy and negligible toxicity, which can be used as a prerequisite for HIV drug resistance global action plan 2017-21. To discover potential hits, we docked 49 antiretroviral analogs (n = 6294) against HIV-1 reverse transcriptase Q151M mutant & its wild-type form and narrow downed their number in three sequential modes of docking using Schrödinger suite...
May 9, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29750364/performance-comparison-of-deep-sequencing-platforms-for-detecting-hiv-1-variants-in-the-pol-gene
#13
Florence Nicot, Nicolas Jeanne, Stéphanie Raymond, Olivier Delfour, Romain Carcenac, Caroline Lefebvre, Karine Sauné, Pierre Delobel, Jacques Izopet
The present study compares the performances of an in-house sequencing protocol on MiSeq to those of the Sanger method, and the 454 GS-FLX for detecting and quantifying drug-resistant mutations in the HIV polymerase gene (reverse transcriptase and protease). MiSeq sequencing identified all the resistance mutations detected by bulk sequencing (n=84). The MiSeq and 454 GS-FLX platforms both identified 67 drug-resistant mutations in the reverse transcriptase and protease regions, but a further 25 drug-resistant mutations were seen by only one or other of them...
May 11, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29746496/pharyngeal-colonization-and-drug-resistance-profiles-of-morraxella-catarrrhalis-streptococcus-pneumoniae-staphylococcus-aureus-and-haemophilus-influenzae-among-hiv-infected-children-attending-art-clinic-of-felegehiwot-referral-hospital-ethiopia
#14
Wondemagegn Mulu, Endalew Yizengaw, Megbaru Alemu, Daniel Mekonnen, Derese Hailu, Kassaw Ketemaw, Bayeh Abera, Mulugeta Kibret
BACKGROUND: Asymptomatic pharyngeal colonization by potential bacteria is the primary reservoir for bacterial species within a population and is considered a prerequisite for development of major childhood diseases such as sinusitis, otitis media, pneumonia, bacteremia, and meningitis. However, there is dearth of data on the colonization and drug resistance pattern of the main bacterial pathogens in the pharynx of HIV infected children in Ethiopia. Therefore, this study determined the pharyngeal colonization and drug resistance profile of bacterial pathogens in HIV infected children attending ART clinic of Felegehiwot Referral Hospital (FHRH), Amhara Region, Ethiopia...
2018: PloS One
https://www.readbyqxmd.com/read/29746295/the-transition-to-dolutegravir-and-other-new-antiretrovirals-in-low-and-middle-income-countries-what-are-the-issues
#15
Marco Vitoria, Andrew Hill, Nathan Ford, Meg Doherty, Polly Clayden, Francois Venter, David Ripin, Charles Flexner, Paul Domanico
: There are currently approximately 16 million people taking NNRTI-based first-line treatment in low- and middle-income countries. Most of these patients are using the combination of tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV). The integrase inhibitor dolutegravir (DTG) has shown an improved safety profile compared to EFV in randomised studies. DTG also has a high barrier to development of drug resistance. New co-formulated tablets with TDF/3TC/DTG are being introduced into LMICs, for a median price of $75 per person-year...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29746294/a-maintenance-three-day-per-week-schedule-with-the-single-tablet-regimen-efavirenz-emtricitabine-tenofovir-disoproxil-fumarate-is-effective-and-decreases-sub-clinical-toxicity-the-a-tri-week-pilot-trial
#16
Jhon Rojas, Jose L Blanco, Sonsoles Sanchez-Palomino, Maria A Marcos, Alberto C Guardo, Ana Gonzalez-Cordon, Montserrat Lonca, Amparo Tricas, Ana Rodriguez, Anabel Romero, Jose M Miro, Josep Mallolas, Jose M Gatell, Montserrat Plana, Esteban Martinez
BACKGROUND: Antiretroviral drugs contained in single tablet Atripla® have pharmacokinetic properties that could allow for longer than once-daily (OD) dosing. We hypothesized that simplifying Atripla® OD to 3-day per week would be feasible, able to maintain viral suppression and less toxic. METHODS: Virologically suppressed (≥2 years) HIV+ adults on Atripla® OD, CD4 >350/mm at inclusion, and no prior documented virological failure or evidence of resistance mutations to efavirenz, tenofovir, or emtricitabine were randomized to maintain their OD regimen or to reduce it to 3 days (Mondays, Wednesdays, and Fridays) a week (3W)...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29746266/ibalizumab
#17
Robert L Bettiker, David E Koren, Jeffrey M Jacobson
PURPOSE OF REVIEW: Antiretroviral options for patients infected with multiclass resistant HIV-1 warrant the development of new agents with unique mechanisms of action and modes of delivery. Here we review one such agent, ibalizumab, a parenteral CD4 postattachment inhibitor that has demonstrated efficacy as part of combination antiretroviral therapy in the treatment of HIV-1. RECENT FINDINGS: In a phase III clinical trial in HIV-infected participants with multiclass antiretroviral drug resistance, the intravenous administration of ibalizumab led to declines in plasma HIV-1 RNA more than 0...
May 8, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29743355/a-novel-gp41-binding-adnectin-with-potent-anti-hiv-activity-is-highly-synergistic-when-linked-to-a-cd4-binding-adnectin
#18
David Wensel, Yongnian Sun, Jonathan Davis, Zhufang Li, Sharon Zhang, Thomas McDonagh, David Fabrizio, Mark Cockett, Mark Krystal
The N17 region of gp41 in HIV-1 is the most conserved region in gp160. mRNA selection technologies were used to identify an Adnectin that binds to this region and inhibits gp41-induced membrane fusion. Additional selection conditions were used to optimize the Adnectin to greater potency (5.4 ± 2.6 nM) to HIV-1 and improved binding affinity to a N17-containing helical trimer (0.8 ± 0.4 nM). Resistance to this Adnectin mapped to a single Glu to Arg change within the N17 coding region. The optimized Adnectin (6200_A08) exhibited high potency and broad spectrum against 123 envelope proteins and multiple clinical isolate viruses, although certain envelope proteins did exhibit reduced susceptibility against 6200_A08 alone...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29742276/hla-b57-01-shields-people-living-with-hiv-for-significantly-better-periodontal-health
#19
Gundolf Schuettfort, Philipp Leuw, Annette Haberl, Eva Herrmann, Kyu-Hyun Park, Timo Wolf, Christoph Stephan
OBJECTIVES: To assess the association between HLA-B57.01 (Human leukocyte antigen) and clinical parameters of chronic periodontitis in people living with HIV (PLWHIV). MATERIALS AND METHODS: All patients were recruited from the HIVCENTER at the Universityhospital Frankfurt during April 2014 and July 2015. Periodontal examination included Periodontal Screening Index (PSI), Gingivalindex (GI), Bleeding on Probing Index (BOP), Periodontal Probing Depth (PD), Clinical Attachment Level (CAL) and DMF-T Score (decayed, missing, filled teeth)...
May 9, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29742132/hiv-drug-resistance-patterns-in-pregnant-women-using-next-generation-sequence-in-mozambique
#20
María Rupérez, Marc Noguera-Julian, Raquel González, Sonia Maculuve, Rocío Bellido, Anifa Vala, Cristina Rodríguez, Esperança Sevene, Roger Paredes, Clara Menéndez
BACKGROUND: Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care. OBJECTIVES: To describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART)...
2018: PloS One
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