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NNRTI HIV

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https://www.readbyqxmd.com/read/28628528/increased-persistence-of-initial-treatment-for-hiv-infection-with-modern-antiretroviral-therapy
#1
Thibaut Davy-Mendez, Joseph J Eron, Oksana Zakharova, David A Wohl, Sonia Napravnik
BACKGROUND: Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic response to initial ART according to the class of anchor agent used. SETTING: An observational clinical cohort study in the Southeastern United States. METHODS: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28627486/the-association-between-detected-drug-resistance-mutations-and-cd4-t-cell-decline-in-hiv-positive-individuals-maintained-on-a-failing-treatment-regimen
#2
Anna Schultze, Roger Paredes, Caroline Sabin, Andrew N Phillips, Deenan Pillay, Nicola Mackie, Antonella Castagna, David Chadwick, Karolin Falconer, Anna Maria Geretti, Frank A Post, Teresa Hill, Ole Kirk, Anton Pozniak, Mark Nelson, Anna Tostevin, David Dunn, Jens Lundgren, Alessandro Cozzi-Lepri
BACKGROUND: To analyse the effect of drug resistance mutations (DRM) on CD4 cell trends in HIV-positive people maintained on virologically failing antiretroviral therapy (ART). METHODS: Individuals from two large cohorts experiencing virological failure (VF) while maintained on ART with >1 CD4 count and >1 resistance test were included. CD4 cell slopes were estimated using linear mixed models. Principal component analysis (PCA) was used to assess the effect of clusters of mutations, defined using extracted component based scores from the PCA, on CD4 cell decline...
June 19, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28600625/an-intravaginal-ring-that-releases-three-antiviral-agents-and-a-contraceptive-blocks-shiv-rt-infection-reduces-hsv-2-shedding-and-suppresses-hormonal-cycling-in-rhesus-macaques
#3
Nina Derby, Meropi Aravantinou, Jessica Kenney, Shweta R Ugaonkar, Asa Wesenberg, Jolanta Wilk, Larisa Kizima, Aixa Rodriguez, Shimin Zhang, Olga Mizenina, Keith Levendosky, Michael L Cooney, Samantha Seidor, Agegnehu Gettie, Brooke Grasperge, James Blanchard, Michael Piatak, Jeffrey D Lifson, José Fernández-Romero, Thomas M Zydowsky, Melissa Robbiani
Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG)...
June 9, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28589720/development-of-a-sp-2-sp-3-stille-cross-coupling-for-rapid-synthesis-of-hiv-nnrti-doravirine-analogues
#4
Abdellatif ElMarrouni, Mark Campbell, James J Perkins, Antonella Converso
The development of a C(sp(2))-C(sp(3)) cross-coupling reaction for rapid, parallel synthesis of analogues of two HIV NNRTI clinical candidates is described. This method allowed easy access to the C-ring space using a practical alkylation with commercially available tributyl(iodomethyl)stannane followed by a palladium-catalyzed coupling with a variety of aryl halides (I, Br) in the presence of copper chloride. Optimization and scope of this method are reported.
June 7, 2017: Organic Letters
https://www.readbyqxmd.com/read/28589513/prevalence-of-hiv-1-transmitted-drug-resistance-in-recently-infected-treatment-na%C3%A3-ve-persons-in-the-southwest-of-iran-2014-2015
#5
Shokouh Ghafari, Arash Memarnejadian, Alireza Samarbaf-Zadeh, Ehsan Mostafavi, Manoochehr Makvandi, Shokrolah Salmanzadeh, Ata Ghadiri, Michael R Jordan, Elham Mousavi, Fatemeh Jahanbakhsh, Kayhan Azadmanesh
The emergence and transmission of drug resistant HIV mutants is a major concern, especially in resource-limited countries with expanding antiretroviral therapy. Studies have recently reported the prevalence of HIV-1 transmitted drug resistance (TDR) mutations in certain Iranian cities; however, no information is currently available about the level of TDR, as well as the nature of the circulating HIV-1 subtypes, in the Southwestern bordering province of Iran, Khuzestan. Herein, we used a WHO-recommended TDR survey method to classify the prevalence of TDR in indigenous people of Khuzestan province...
June 6, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28585361/prevalence-of-hiv-1-transmitted-drug-resistance-in-the-incarcerated-population
#6
J Sapozhnikov, J D Young, M Patel, T D Chiampas, P Vaughn, M E Badowski
OBJECTIVES: The aim of the study was to determine the prevalence of transmitted drug resistance (TDR)-associated mutations among treatment-naïve, incarcerated individuals with HIV-1 infection in the USA as well as the class TDR and antiretroviral (ARV) mutations present at baseline. METHODS: Patients over the age of 18 years were included in the study if they had been diagnosed with HIV infection, if their HIV infection was managed through telemedicine and if they were incarcerated in the State of Illinois Department of Corrections between 10 July 2010 and 29 April 2016...
June 6, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28582463/drug-resistance-testing-through-remote-genotyping-and-predicted-treatment-options-in-human-immunodeficiency-virus-type-1-infected-tanzanian-subjects-failing-first-or-second-line-antiretroviral-therapy
#7
Jenny Svärd, Sabina Mugusi, Doreen Mloka, Ujjwal Neogi, Genny Meini, Ferdinand Mugusi, Francesca Incardona, Maurizio Zazzi, Anders Sönnerborg
INTRODUCTION: Antiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered...
2017: PloS One
https://www.readbyqxmd.com/read/28569550/ultra-deep-sequencing-analysis-on-hiv-drug-resistant-associated-mutations-among-hiv-infected-individuals-first-report-from-the-philippines
#8
Ivo Novita SahBandar, Genesis Samonte, Elizabeth Telan, Nalyn Siripong, Mahdi Belcaid, David Schanzenbach, Susan Leano, Haorile Chagan-Yasutan, Toshio Hattori, Cecilia Shikuma, Lishomwa C Ndhlovu
OBJECTIVE: A sharp increase in the number of people living with HIV (PLHIV) has been documented in the Philippines. In response, the government has instituted antiretroviral therapy (ART) nationwide through HIV treatment hubs. However, no data presently exists on the status of ART drug-resistant-associated mutations (DRMs). In this study, we aim to analyze DRM profiles in the Philippines and provide comprehensive data on DRMs to guide treatment decisions and prevent viral failures. DESIGN AND METHODS: We conducted a cross-sectional study in 119 volunteers tested positive for HIV from over 8,000 participants screened for HIV across the nation through 2013 Integrated HIV Behavioral and Serologic Surveillance (IHBSS) program...
June 1, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28553415/use-of-proviral-dna-to-investigate-virus-resistance-mutations-in-hiv-infected-zimbabweans
#9
Tutsirai V Musingwini, Danai T Zhou, Doreen Mhandire, Kerina Duri, Exnevia Gomo, Olav Oktedalen, Benjamin Chimukangara, Tinei Shamu, Sandra Shawarira-Bote, Collet Dandara, Babill Stray-Pedersen
BACKGROUND: Antiretroviral therapy (ART) to suppress HIV replication has reduced morbidity and mortality yet effectiveness of current HIV drugs is threatened by HIV drug resistance (HIVDR) mutations. OBJECTIVE: To determine HIVDR mutations using proviral DNA from specimens of patients presenting to an HIV treatment clinic. METHODS: DNA from 103 patients, 86 treatment-experienced, 17 treatment-naïve, were genotyped for the HIV-1C reverse transcriptase gene (RT; codons 21-304) using Sanger sequencing and sequences analyzed using Sequencher software...
2017: Open Microbiology Journal
https://www.readbyqxmd.com/read/28539254/prevalence-of-primary-resistance-among-acutely-recently-hiv-infected-patients-in-rio-de-janeiro-brazil
#10
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/28521719/virological-suppression-and-patterns-of-resistance-amongst-patients-on-antiretroviral-therapy-at-4-nigerian-military-hospitals
#11
Babajide Keshinro, Ojor Ayemoba, Kene Terfa, Julie Ake, Trevor A Crowell, Yakubu Adamu, Tahir Mohammed, Ifeanyi Okoye, Sunday Odeyemi, Keith Crawford, Lindsay Hughes, Ezekiel Akintunde, Tahir Umar, Tiffany E Hamm, Ogbonnaya S Njoku
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
#12
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
https://www.readbyqxmd.com/read/28507107/in-vitro-cross-resistance-profiles-of-rilpivirine-dapivirine-and-miv-150-nnrti-microbicides-in-clinical-development-for-the-prevention-of-hiv-1-infection
#13
Nicholas S Giacobbi, Nicolas Sluis-Cremer
Rilpivirine, dapivirine (DPV) and MIV-150 are in development as microbicides. It is not known whether they will block infection of circulating NNRTI-resistant HIV-1 variants. Here, we demonstrate that the activity of DPV and MIV-150 are compromised by many resistant viruses containing single or double substitutions. High DPV genital tract concentrations from DPV-ring use may block replication of resistant viruses. However, MIV-150 genital tract concentrations may be insufficient to inhibit many resistant viruses, including those harboring K103N or Y181C...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28505015/virologic-response-to-first-line-efavirenz-or-nevirapine-based-antiretroviral-therapy-in-hiv-infected-african-children
#14
Adeodata Kekitiinwa, Alexander J Szubert, Moira Spyer, Richard Katuramu, Victor Musiime, Tawanda Mhute, Sabrina Bakeera-Kitaka, Oscar Senfuma, Ann Sarah Walker, Diana M Gibb
BACKGROUND: Poorer virologic response to nevirapine- versus efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies. METHODS: We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine versus efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/mL at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (P = 0...
June 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28482025/patterns-of-transmitted-drug-resistance-and-virological-response-to-first-line-antiretroviral-treatment-among-hiv-positive-people-who-use-illicit-drugs-in-a-canadian-setting
#15
M Eugenia Socías, Ekaterina Nosova, Thomas Kerr, Kanna Hayashi, P Richard Harrigan, Jeannie Shoveller, Julio Montaner, M-J Milloy
Background: Transmitted drug resistance (TDR) may compromise response to antiretroviral treatment (ART). However, there is limited data on TDR patterns and impacts among people who use illicit drugs (PWUD). Methods: Data was drawn from two prospective cohorts of PWUD in Vancouver, Canada. We characterized patterns of TDR among HIV-positive PWUD, and assessed its impacts on first-line ART virological outcomes. Results: Between 1996-2015, among 573 ART-naïve PWUD (18% with recent HIV infection), the overall TDR prevalence was 9...
May 6, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28481112/structure-based-optimization-of-thiophene-3-2-d-pyrimidine-derivatives-as-potent-hiv-1-non-nucleoside-reverse-transcriptase-inhibitors-with-improved-potency-against-resistance-associated-variants
#16
Dongwei Kang, Zengjun Fang, Boshi Huang, Xueyi Lu, Heng Zhang, Haoran Xu, Zhipeng Huo, Zhongxia Zhou, Zhao Yu, Qing Meng, Gaochan Wu, Xiao Ding, Ye Tian, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
This work follows on from our initial discovery of a series of piperidine-substituted thiophene[3,2-d]pyrimidine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) ( J. Med. Chem. 2016 , 59 , 7991 - 8007 ). In the present study, we designed, synthesized, and biologically tested several series of new derivatives in order to investigate previously unexplored chemical space. Some of the synthesized compounds displayed single-digit nanomolar anti-HIV potencies against wild-type (WT) virus and a panel of NNRTI-resistant mutant viruses in MT-4 cells...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28474534/evolution-of-hiv-1-surveillance-drug-resistance-mutations-over-ten-years-in-new-south-wales-australia
#17
Angie Pinto, Alex Carrera, Hanan Salem, Kiran Thapa, Ansari Shaik, Kathy Petoumenos, Philip Cunningham, Roger Garsia, Dominic Dwyer, David A Cooper, Anthony D Kelleher
New South Wales (NSW) has the greatest burden of HIV in Australia, with 2012 and 2013 recording the highest rates of new diagnoses in twenty years. Concurrently, there has been significant changes in antiretorviral treatments and testing paradigms. We compiled a statewide resistance database to characterize changes in HIV-1 resistance mutations over time. Genotypic antiretroviral resistance testing (GART) was performed on request at three reference laboratories using commercial and in house methods. 7629 HIV-1 polymerase sequences obtained from GART from 2004-2013 were retrospectively collated, reformatted, de-identified and analysed using Stanford HIVdb program 7...
May 5, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28453836/commonly-transmitted-hiv-1-drug-resistance-mutations-in-reverse-transcriptase-and-protease-in-antiretroviral-treatment-naive-patients-and-response-to-regimens-containing-tenofovir-disoproxil-fumarate-or-tenofovir-alafenamide
#18
Nicolas A Margot, Pamela Wong, Rima Kulkarni, Kirsten White, Danielle Porter, Michael E Abram, Christian Callebaut, Michael D Miller
Background.: The presence of transmitted drug resistance mutations (TDRMs) in antiretroviral treatment (ART)-naive patients can adversely affect the outcome of ART. Methods.: Resistance testing was conducted in 6704 ART-naive subjects predominantly from the United States and Europe in 9 clinical studies conducted by Gilead Sciences from 2000 to 2013. Results.: The presence of TDRMs increased during this period (from 5.2% to 11.4%), primarily driven by an increase in nonnucleoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations (from 0...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28453027/-prevalence-of-potential-drug-drug-interactions-involving-antiretroviral-drugs-in-buenos-aires-argentina
#19
Ezequiel Córdova, Norma Porteiro, Eliana Loiza, Horacio Mingrone
INTRODUCTION: Antiretroviral agents (ARVs) have a high potential for drug interactions. However, the prevalence and risk factors for clinically significant drug-drug interactions (CSDDIs) with ARVs from Latin American countries is unknown. AIM: To evaluate the prevalence and risk factors for CSDDIs in HIV outpatients attending at two centers in Buenos Aires, Argentina. METHODS: Descriptive cross-sectional study (september to november 2012)...
October 2016: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/28434406/efavirenz-based-simplification-after-successful-early-lopinavir-boosted-ritonavir-based-therapy-in-hiv-infected-children-in-burkina-faso-and-c%C3%A3-te-d-ivoire-the-monod-anrs-12206-non-inferiority-randomised-trial
#20
Désiré Lucien Dahourou, Madeleine Amorissani-Folquet, Karen Malateste, Clarisse Amani-Bosse, Malik Coulibaly, Carole Seguin-Devaux, Thomas Toni, Rasmata Ouédraogo, Stéphane Blanche, Caroline Yonaba, François Eboua, Philippe Lepage, Divine Avit, Sylvie Ouédraogo, Philippe Van de Perre, Sylvie N'Gbeche, Angèle Kalmogho, Roger Salamon, Nicolas Meda, Marguerite Timité-Konan, Valériane Leroy
BACKGROUND: The 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years...
April 24, 2017: BMC Medicine
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