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Resistance hiv

Emma D Deeks
Doravirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Merck & Co for the treatment of HIV-1 infection. The drug is approved in the USA both as a single-agent tablet (Pifeltro™) and as a fixed-dose combination tablet with the nucleos(t)ide reverse transcriptase inhibitors lamivudine and tenofovir disoproxil fumarate (Delstrigo™). Each formulation is indicated in the USA for treating HIV-1 infection in adults with no prior antiretroviral treatment, has received a positive opinion in the EU for treating HIV-1 infection in adults without resistance to NNRTIs or (in the case of the fixed-dose combination tablet) lamivudine or tenofovir, and is also under regulatory review for the treatment of HIV-1 infection in Canada...
October 19, 2018: Drugs
Ivan Surya Pradipta, Lina Davies Forsman, Judith Bruchfeld, Eelko Hak, Jan-Willem Alffenaar
OBJECTIVES: Since the risk of multidrug-resistant tuberculosis (MDR-TB) may depend on the setting, we aimed to determine the associations of risk factors of MDR-TB across different regions. METHODS: A systematic review and meta-analysis was performed with Pubmed and Embase databases. Information was retrieved on 37 pre-defined risk factors of MDR-TB. We estimated overall Mantel-Haenszel odds ratio as a measure of the association. RESULTS: Factors of previous TB disease and treatment are the most important risk factors associated with MDR-TB...
October 16, 2018: Journal of Infection
Nisha Chokkar, Sourav Kalra, Monika Chauhan, Raj Kumar
After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV) infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery is marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor...
October 18, 2018: Mini Reviews in Medicinal Chemistry
Christiane Horwood, Ngcwalisa Amanda Jama, Lyn Haskins, Anna Coutsoudis, Lenore Spies
Despite efforts to support breastfeeding for HIV-positive mothers in South Africa, being HIV-positive remains a barrier to initiating and sustaining breastfeeding. The aim was to explore decision-making about infant feeding practices among HIV-positive mothers in a rural and urban setting in KwaZulu-Natal, South Africa. HIV-positive pregnant women were purposively sampled from one antenatal clinic in each setting. A qualitative, longitudinal cohort design was employed, with monthly in-depth interviews conducted over six months post-delivery...
October 19, 2018: Maternal & Child Nutrition
Dong-Rong Yi, Ni An, Zhen-Long Liu, Feng-Wen Xu, Kavita Raniga, Quan-Jie Li, Rui Zhou, Jing Wang, Yong-Xin Zhang, Jin-Ming Zhou, Lei-Liang Zhang, Jing An, Cheng-Feng Qin, Fei Guo, Xiao-Yu Li, Chen Liang, Shan Cen
Type I interferon (IFN) inhibits viruses through inducing the expression of antiviral proteins. The IFN-induced myxovirus resistance B (MxB) protein has been reported to inhibit a limited number of viruses including HIV-1 and herpesviruses, its antiviral coverage remains to be further explored. Here, we find that MxB interferes with RNA replication of Hepatitis C virus (HCV) and significantly inhibits viral replication in a cyclophilin A (CypA)-dependent manner. Our data further show that MxB interacts with HCV protein NS5A, thereby impairing NS5A interaction with CypA and NS5A localization to the endoplasmic reticulum, two events essential for HCV RNA replication...
October 17, 2018: Journal of Virology
A K Halder
Multiple Quantitative Structure-Activity Relationship (QSAR) analysis is widely used in drug discovery for lead identification. Human Immunodeficiency Virus (HIV) protease is one of the key targets for the treatment of Acquired Immunodeficiency Syndrome (AIDS). One of the major challenges for the design of HIV-1 protease inhibitors (HIV PRIs) is to increase the inhibitory activities against the enzyme to a level where the problem associated to drug resistance may be considerably delayed. Herein, chemometric analyses were performed with 346 structurally diverse HIV PRIs with experimental bioactivities against a sub-type B mutant to develop highly predictable QSAR models and also to identify the effective structural determinants for higher affinity against HIV PR...
November 2018: SAR and QSAR in Environmental Research
M Verdecchia, K Keus, S Blankley, D Vambe, C Ssonko, T Piening, E C Casas
INTRODUCTION: Since 2011 Médecins sans Frontières together with the eSwatini Ministry of Health have been managing patients with multi-drug resistant tuberculosis (MDR-TB) at Matsapha and Mankayane in Manzini region. This analysis describes the model of care and outcomes of patients receiving a 20 months MDR-TB treatment regimen between 2011 and 2013. METHOD: We conducted a retrospective observational cohort study of MDR-TB patients enrolled for treatment between May 2011 and December 2013...
2018: PloS One
Alfred Andama, Akos Somoskovi, Brinnon Mandel, David Bell, Cristina Gutierrez
Tuberculosis (TB) recently surpassed HIV/AIDS as the deadliest infectious disease. Despite some advancements in technologies and programs, TB remains a global health epidemic that, without significant gains in better diagnostic and management, will not abate. This review describes the molecular diagnostic gaps, needs, and potential solutions for improving access to diagnosis and management of patients with drug susceptible and drug resistant TB. The ultimate goal is to improve laboratory diagnostics and better individualized managementof detected TB, and make an important contribution toward eliminating this global epidemic...
October 13, 2018: Infection, Genetics and Evolution
Neta S Zuckerman, Zohar Mor, Efrat Bucris, Marina Wax, Ella Mendelson, Orna Mor
OBJECTIVES: Men who have sex with men (MSM) comprise ∼30% of new HIV infections in Israel, a country with mixed Jewish and Arab populations. We molecularly characterized HIV-1 in the Arab and Jewish MSM (AMSM, JMSM) populations to reveal possible inter-ethnical connections. DESIGN: Cross-sectional study METHODS:: All Israeli-born, HIV-1-infected MSM diagnosed between 2005 and 2016 (n = 1143) were cross-matched with the National Civil Registry to identify religion (Jews/Muslim/Christian)...
October 15, 2018: AIDS
Anna Schultze, Carlo Torti, Alessandro Cozzi-Lepri, Anne-Mieke Vandamme, Maurizio Zazzi, Helen Sambatakou, Andrea De Luca, Anna Maria Geretti, Anders Sonnerborg, Lidia Ruiz, Laura Monno, Simona Di Giambenedetto, Andrea Gori, Giuseppe Lapadula
OBJECTIVE: To evaluate the effect of primary resistance and selected polymorphic amino-acid substitutions in HIV reverse transcriptase (RT) and protease (PR) on the CD4 count and viral load (VL) set point before the start of ART. DESIGN: Prospective cohort study. METHODS: 6,180 individuals with a resistance test prior to starting ART accessing care in HIV clinics across Europe who had at least 1 VL and 1 CD4 test available were included in the analysis...
October 15, 2018: AIDS
Priscila Cristina Bartolomeu Halicki, Gabriela Hädrich, Raphael Boschero, Laís Andrade Ferreira, Andrea von Groll, Pedro Eduardo Almeida da Silva, Cristiana Lima Dora, Daniela Fernandes Ramos
Tuberculosis (TB) is considered an emergency global public health, mainly due to the TB-HIV co-infection, bacillus dormancy stage, and emergence of resistant strains. In addition, the therapeutic toxicity and its pharmacokinetic interactions with other drugs may influence treatment non-compliance, low serum concentration of drugs, and, consequently, treatment failure. Strategies using nanotechnology represent a new tool for the therapy, since they are effective delivery systems due to the possibility of solubilization of hydrophobic compounds, enable the production of formulations for oral use, and, in addition, increase bioavailability of drugs...
October 16, 2018: Assay and Drug Development Technologies
Mingze Su, Lingjie Liao, Hui Xing, Shuai Wang, Yutang Li, Wei Lu, Lingyuan He, Juan Deng, Yiming Shao, Tong Li, Hui Zhuang
Purpose: This study aimed to investigate the HIV and hepatitis B virus (HBV) co-infection in three HIV high endemic areas with different modes of HIV transmission and explore the HBV nucleos(t)ide analogue resistance (NUCr) substitutions in this cohort receiving antiretroviral therapy (ART). Patients and methods: The enrolled 705 HIV-infected patients were from three different regions in China and received lamivudine-based ART for at least 1 year. After screening for hepatitis B surface antigen (HBsAg), the hepatitis B e antigen (HBeAg), and antibody against hepatitis B core antigen (anti-HBc and anti-HBc IgM), HBV DNA in plasma of patients positive for HBsAg was tested...
2018: Infection and Drug Resistance
Bremansu Osa-Andrews, Kee W Tan, Angelina Sampson, Surtaj H Iram
Multidrug resistance protein 1 (MRP1) can efflux a wide variety of molecules including toxic chemicals, drugs, and their derivatives out of cells. Substrates of MRP1 include anti-cancer agents, antibiotics, anti-virals, anti-human immunodeficiency virus (HIV), and many other drugs. To identify novel substrates and modulators of MRP1 by exploiting intramolecular fluorescence resonance energy transfer (FRET), we genetically engineered six different two-color MRP1 proteins by changing green fluorescent protein (GFP) insertion sites, while keeping the red fluorescent protein (RFP) at the C-terminal of MRP1...
October 13, 2018: Pharmaceutics
Anne Derache, Collins C Iwuji, Kathy Baisley, Siva Danaviah, Anne-Geneviève Marcelin, Vincent Calvez, Tulio de Oliveira, François Dabis, Kholoud Porter, Deenan Pillay
Background: Previous studies in HIV-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS) [<50copies/mL] in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a Treatment as Prevention trial. Methods: Among 1,557 HIV-positive individuals reporting no prior ART at study entry and provided plasma samples, 1,328 individuals with entry viral load (VL) >1,000 copies/mL had next generation sequencing (NGS) of the HIV pol gene with MiSeq technology...
October 15, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ranmini S Kularatne, Ronelle Niit, Jane Rowley, Tendesayi Kufa-Chakezha, Remco P H Peters, Melanie M Taylor, Leigh F Johnson, Eline L Korenromp
OBJECTIVES: To estimate trends in prevalence and incidence of syphilis, gonorrhea and chlamydia in adult men and women in South Africa. METHODS: The Spectrum-STI tool estimated trends in prevalence and incidence of active syphilis, gonorrhea and chlamydia, fitting South African prevalence data. Results were used, alongside programmatic surveillance data, to estimate trends in incident gonorrhea cases resistant to first-line treatment, and the reporting gap of symptomatic male gonorrhea and chlamydia cases treated but not reported as cases of urethritis syndrome...
2018: PloS One
KaiJun Jin, YaLi Sang, Erik De Clercq, Christophe Pannecouque, Ge Meng
A novel series of substituted piperazine-1-yl-pyrimidine derivatives were designed and synthesized as a new type of HIV-1 non-nucleoside inhibitors. Various N-substituted aromatic groups were incorporated into the piperazine ring through a simple and practical route to investigate the biological activity of these target compounds against wild-type and resistant strains of HIV-1. All of the target compounds were also evaluated as HIV-1 reverse transcriptase inhibitors in MT-4 cell cultures. The biological results showed that six of these compounds displayed inhibitory activities against the wild-type strain, among of which 7q and 7t were found to be the two most active analogues possessing EC50 values of 31...
October 9, 2018: Bioorganic & Medicinal Chemistry Letters
Melanie Stecher, Antoine Chaillon, Anna Maria Eis-Hübinger, Clara Lehmann, Gerd Fätkenheuer, Jan-Christian Wasmuth, Elena Knops, Jörg Janne Vehreschild, Sanjay Mehta, Martin Hoenigl
OBJECTIVES: In Germany, previous reports have demonstrated transmitted HIV-1 drug resistance mutations (DRM) in 11% of newly diagnosed individuals, highlighting the importance of drug-resistance screening prior to initiation of antiretroviral therapy (ART). Here, we sought to understand the molecular epidemiology of HIV DRM transmission in the Cologne-Bonn region of Germany, given one of the highest rates of new HIV diagnoses in Western Europe (13.7 per 100,000 habitants). METHODS: We analysed 714 HIV-1 ART naïve infected individuals diagnosed at the University Hospitals Cologne and Bonn between 2001 and 2016...
October 10, 2018: Clinical Microbiology and Infection
Adhikarimayum Lakhikumar Sharma, Thiyam Ramsing Singh, Lisam Shanjukumar Singh
Increasing incidence of drug resistance is ascertained to be the main obstacles in limiting the virus among the human immunodeficiency virus (HIV) infected individuals. This study investigates the drug resistance mutations (DRMs), genetic variants and origin of transmitted drug resistance of HIV-1 among the HIV-1 infected wives of intravenous drug users (IDUs) in Manipur. 44 HIV pol gene sequences were generated from 56 blood samples by viral gene amplification and sequencing. Sequences were then analysed for drug resistance, genetic variants and origin...
October 12, 2018: Scientific Reports
Marta Iglis Oliveira, Valter Romão de Souza Junior, Claudia Fernanda de Lacerda Vidal, Paulo Sérgio Ramos de Araújo
BACKGROUND: Incomplete virologic suppression results in mutations associated with resistance and is a major obstacle to disease control. We analyzed the genotypic profiles of HIV-1 patients at the time of the first virologic failure and the response to a salvage regimen after 48 weeks. METHODS: This work was a cross-sectional, retrospective, analytical study based on data collected from medical records and genotyping tests between 2006 and 2016. The sample consisted of data on individuals living with HIV (PLWH) from three major reference centers...
October 12, 2018: BMC Infectious Diseases
Lola Madrid, Sonia Amós Maculuve, Alba Vilajeliu, Emma Sáez, Sergio Massora, Anelsio Cossa, Rosauro Varo, Antonio Sitoe, Noraida Mosqueda, Rui Anselmo, Khatia Munguambe, Sara M Soto, Cinta Moraleda, Eusebio Macete, Clara Menéndez, Quique Bassat
BACKGROUND: In low-income countries, data on prevalence and effects of group B Streptococcus (GBS) and Escherichia coli (E. coli) colonization among pregnant women are scarce, but necessary to formulate prevention strategies. We assessed prevalence of GBS and E. coli colonization and factors associated among pregnant women, its effect in newborns and acceptability regarding the utilized sampling methods in a semirural Mozambican hospital. METHODS: Pregnant women were recruited from June 2014 to January 2015, during routine antenatal clinics at gestational age ≥ 34 weeks (n = 200); or upon delivery (n = 120)...
November 2018: Pediatric Infectious Disease Journal
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