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hiv resistance

Jennifer A Fulcher, Yushen Du, Tian-Hao Zhang, Ren Sun, Raphael J Landovitz
Dolutegravir (DTG) is a preferred drug for initial treatment of human immunodeficiency virus type 1 infection. We present next-generation sequencing analysis of integrase genotypes during a period of virologic failure in a treatment-naive man who initiated tenofovir disoproxil fumarate/emtricitabine plus DTG.
March 21, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
B Rossetti, S Di Giambenedetto, C Torti, M C Postorino, G Punzi, F Saladini, W Gennari, V Borghi, L Monno, A R Pignataro, E Polilli, M Colafigli, A Poggi, S Tini, M Zazzi, A De Luca
OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences...
June 22, 2018: HIV Medicine
D Sculier, T Doco-Lecompte, S Yerly, K J Metzner, L A Decosterd, A Calmy
OBJECTIVES: Dolutegravir (DTG) is a highly effective integrase inhibitor with a strong genetic resistance barrier and a potential role in simplified HIV maintenance treatment. We assessed the feasibility of DTG maintenance monotherapy and measured HIV reservoirs on DTG monotherapy. METHODS: An interventional, open-label, single-arm study including eight virologically suppressed HIV-1-infected patients switched to DTG 50 mg once daily for 24 weeks was performed...
June 22, 2018: HIV Medicine
Gaëlle F Tchouwa, Sabrina Eymard-Duvernay, Amandine Cournil, Nadine Lamare, Laetitia Serrano, Christelle Butel, Silvia Bertagnolio, Eitel Mpoudi-Ngole, Elliot Raizes, Avelin F Aghokeng
Background: Pretreatment HIV drug resistance (PDR) has the potential to affect treatment outcome and mortality. We present here the first nationally representative PDR study conducted in Cameroon. Methods: From February to July 2015, HIV-infected ART initiators were recruited from 24 randomly selected clinics situated in both urban and rural regions. Dried blood spot specimens were collected from study participants at these clinics and centralized in a reference laboratory in Yaoundé, Cameroon, for drug resistance testing...
June 19, 2018: Journal of Antimicrobial Chemotherapy
Danwei Yu, Xiaohui Ding, Zixian Liu, Xiyuan Wu, Yuanmei Zhu, Huamian Wei, Huihui Chong, Sheng Cui, Yuxian He
Host cell infection with HIV-1 requires fusion of viral and cell membranes. Sifuvirtide (SFT) is a peptide-based HIV-1 fusion inhibitor approved for phase III clinical trials in China. Here, we focused on characterizing HIV-1 variants highly resistant to SFT to gain insight into the molecular resistance mechanism. Three primary substitutions (V38A, A47I, and Q52R) located at the inhibitor-binding site of HIV-1's envelope protein (Env) and one secondary substitution (N126K) located at the C-terminal heptad repeat region of the viral protein gp41, which is part of the envelope, conferred high SFT resistance and cross-resistance to the anti-HIV-1 drug T20 and the template peptide C34...
June 21, 2018: Journal of Biological Chemistry
Maxime Beretta, Alain Moreau, Mélanie Bouvin-Pley, Asma Essat, Cécile Goujard, Marie-Laure Chaix, Stéphane Hue, Laurence Meyer, Francis Barin, Martine Braibant
OBJECTIVE: Transmission of HIV-1 involves a bottleneck in which generally a single HIV-1 variant from a diverse viral population in the transmitting partner establishes infection in the new host. It is still unclear to what extent this event is driven by specific properties of the transmitted viruses or the result of a stochastic process. Our study aimed to better characterize this phenomenon and define properties shared by transmitted viruses. DESIGN: We compared antigenic and functional properties of envelope glycoproteins of viral variants found during primary infection in 27 patients belonging to eight transmission chains...
June 20, 2018: AIDS
Bin Xu, Qinghua Pan, Chen Liang
Type I interferon inhibits viruses through inducing the expression of antiviral proteins, including the myxovirus resistance (Mx) proteins. Compared to human MxA protein that inhibits a wide range of viruses, the MxB protein has been reported to specifically inhibit primate lentiviruses including HIV-1, and herpesviruses. Further, the role of endogenous MxB in interferon-α mediated inhibition of HIV-1 infection was questioned by a recent study showing that MxB knockout did not increase the infection of HIV-1 which carried the G protein of vesicular stomatitis virus (VSV), and thus was able to infect CD4-negative HT1080 cells...
June 20, 2018: Journal of Virology
Janis A Müller, Anna Glöckle, Ali Gawanbacht, Matthias Geyer, Jan Münch, Frank Kirchhoff
VIRIP has been identified as natural HIV-1 inhibitor targeting the gp41 fusion peptide. An optimized analogue (VIR-576) was effective in a phase I/II clinical trial and initial studies showed that HIV-1 resistance to VIRIP-based inhibitors has a high genetic barrier. Partially resistant CXCR4(X4)-tropic HIV-1 NL4-3 variants could be obtained, however, after more than 15 months of passaging in MT-4 cells in the presence of another derivative (VIR-353). Sequence analysis identified the accumulation of seven mutations across the HIV-1 envelope glycoprotein but outside of the gp41 fusion peptide...
June 20, 2018: Journal of Virology
Eric S Daar, Edwin DeJesus, Peter Ruane, Gordon Crofoot, Godson Oguchi, Catherine Creticos, Jürgen K Rockstroh, Jean-Michel Molina, Ellen Koenig, Ya-Pei Liu, Joseph Custodio, Kristen Andreatta, Hiba Graham, Andrew Cheng, Hal Martin, Erin Quirk
BACKGROUND: Switching from therapy based on a boosted protease inhibitor to bictegravir, emtricitabine, and tenofovir alafenamide could avoid drug interactions and unwanted side-effects in virologically suppressed adults with HIV-1 infection, while maintaining a high barrier to resistance and providing a simplified once-daily, single-tablet regimen. Here, we report 48 week results of a phase 3 study investigating this switch. METHODS: In this multicentre, randomised, open-label, active-controlled, non-inferiority, phase 3 trial, adults with HIV-1 infection were enrolled at 121 outpatient centres in ten countries...
June 15, 2018: Lancet HIV
Jean-Michel Molina, Douglas Ward, Indira Brar, Anthony Mills, Hans-Jürgen Stellbrink, Luis López-Cortés, Peter Ruane, Daniel Podzamczer, Cynthia Brinson, Joseph Custodio, Hui Liu, Kristen Andreatta, Hal Martin, Andrew Cheng, Erin Quirk
BACKGROUND: Bictegravir, co-formulated with emtricitabine and tenofovir alafenamide, has shown good efficacy and tolerability, and similar bone, renal, and lipid profiles to dolutegravir, abacavir, and lamivudine, in treatment-naive adults with HIV-1 infection, without development of treatment-emergent resistance. Here, we report 48-week results of a phase 3 study investigating switching to bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir, abacavir, and lamivudine in virologically suppressed adults with HIV-1 infection...
June 15, 2018: Lancet HIV
Emma D Deeks
Darunavir/cobicistat/emtricitabine/tenofovir AF (Symtuza® ) is the first protease inhibitor (PI)-based single-tablet regimen (STR) available for the treatment of adults and adolescents (aged ≥ 12 years) with HIV-1 infection. It combines the PI darunavir (which has a high genetic barrier to resistance) with the pharmacokinetic booster cobicistat and the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (tenofovir AF), the latter being associated with less off-target tenofovir exposure than its predecessor tenofovir disoproxil fumarate (tenofovir DF)...
June 18, 2018: Drugs
Yeonjae Kim, Bum Sik Chin, Gayeon Kim, Hyoung-Shik Shin
The present study investigated prevalence of integrase strand transfer inhibitors (INSTI) resistance mutations in HIV-1-infected antiretroviral therapy (ART)-naïve patients in Korea. From 106 plasma samples, amplification and sequencing of integrase genes was performed, and major or minor mutations were calculated by the Stanford HIV drug resistance mutation interpretation algorithm. No major INSTI resistance mutations were found, and 14 minor mutations were detected in 13 (12.3%) patients. The present data support the recommendation that routine testing for INSTI resistance mutations before starting ART is not necessary...
June 18, 2018: Journal of Korean Medical Science
Natapol Pumipuntu, Supawadee Piratae
Cryptosporidiosis is considered to be a crucial zoonotic disease caused by worldwide distributing parasitic protozoa called Cryptosporidium spp. Cryptosporidiosis becomes a major public health and veterinary concern by affecting in human and various host range species of animals. Essentially, its importance of infection is increasing because of the high incidence in young children, immunocompromised persons, or immunodeficiency syndrome patients, especially in HIV/AIDS, and it is also one of the most causes of mortality in those patients who infected with Cryptosporidium spp...
May 2018: Veterinary World
Navid Madani, Amy M Princiotto, Linh Mach, Shilei Ding, Jérémie Prevost, Jonathan Richard, Bhavna Hora, Laura Sutherland, Connie A Zhao, Brandon P Conn, Todd Bradley, M Anthony Moody, Bruno Melillo, Andrés Finzi, Barton F Haynes, Amos B Smith Iii, Sampa Santra, Joseph Sodroski
The envelope glycoprotein (Env) trimer ((gp120/gp41)3 ) mediates human immunodeficiency virus (HIV-1) entry into cells. The "closed," antibody-resistant Env trimer is driven to more open conformations by binding the host receptor, CD4. Broadly neutralizing antibodies that recognize conserved elements of the closed Env are potentially protective, but are elicited inefficiently. HIV-1 has evolved multiple mechanisms to evade readily elicited antibodies against more open Env conformations. Small-molecule CD4-mimetic compounds (CD4mc) bind the HIV-1 gp120 Env and promote conformational changes similar to those induced by CD4, exposing conserved Env elements to antibodies...
June 18, 2018: Nature Communications
Tatiana Metcalf, Jaime Soria, Silvia M Montano, Eduardo Ticona, Carlton A Evans, Luz Huaroto, Matthew Kasper, Eric S Ramos, Nicanor Mori, Podjanee Jittamala, Kesinee Chotivanich, Irwin F Chavez, Pratap Singhasivanon, Sasithon Pukrittayakamee, Joseph R Zunt
BACKGROUND: Meningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM). METHODS: Patients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M...
2018: PloS One
José M Gatell, Lambert Assoumou, Graeme Moyle, Laura Waters, Margaret Johnson, Pere Domingo, Julie Fox, Esteban Martinez, Hans-Jürgen Stellbrink, Giovanni Guaraldi, Mar Masia, Mark Gompels, Stephane De Wit, Eric Florence, Stefan Esser, François Raffi, Christoph Stephan, Juergen Rockstroh, Andrea Giacomelli, Jaime Vera, José Ignacio Bernardino, Alan Winston, Maria Saumoy, Julien Gras, Christine Katlama, Anton L Pozniak
Background: Both immediate or deferred switching from a PI/r to DTG may improve lipid profile. Methods: NEAT022 is a European, open label, randomized, trial. HIV-infected adults ≥ 50 years or with a Framingham score ≥10% were eligible if HIV RNA < 50 copies/mL. Patients were randomized to switch the PI/r to DTG immediately (DTG-I) or to deferred switch at week 48 (DTG-D) . Week 96 end-points were: proportion of patients with HIV RNA < 50 copies/ml, percentage change of lipid fractions and adverse events...
June 14, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
S A Hart, S Vardhanabhuti, S A Strobino, L J Harrison
IntroductionThe Stanford HIV-1 genotypic resistance interpretation algorithm has changed substantially over its lifetime. In many studies the algorithm version used is not specified. It is easy to assume results across versions are comparable, but the effects of version changes on resistance calls are unknown. We evaluate these effects for 20 antiretroviral drugs.MethodsWe calculated resistance interpretations for the same 5,993 HIV-1 sequences, from participants in AIDS Clinical Trials Group studies, under 14 versions of the Stanford algorithm from 2002 to 2017...
June 14, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Tanja Engel, Marieke Raffenberg, Catia Marzolini, Matthias Cavassini, Helen Kovari, Barbara Hasse, Philip E Tarr
Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to "metabolic" complications (insulin resistance, dyslipidemia, osteoporosis, and others). Studies suggested increased rates of myocardial infarction, renal insufficiency, neurocognitive dysfunction, and fractures in HIV-postitive patients. Even long-term suppression of HIV seemed to be accompanied by an excess of deleterious inflammation that could promote these complications. The aims of this viewpoint paper are to summarize recent data and to examine the possibility that the problem of aging-related morbidity in HIV might not be as dramatic as previously believed...
June 15, 2018: Gerontology
Vanessa El Kamari, Corrilynn O Hileman, Pierre M Gholam, Manjusha Kulkarni, Nicholas Funderburg, Grace A McComsey
BACKGROUND & AIMS: Therapies are needed to limit progression of fatty liver diseases in patients with HIV infection. We analyzed data from a prospective study of the effects of rosuvastatin (a statin) on hepatic steatosis in HIV-positive adults. METHODS: We performed secondary analysis of data from a double-blind trial of adult patients with HIV infection (78% male; 68% African American; mean age, 46 years; body mass index, 29 kg/m2 ; HIV1 RNA<1000 copies/mL; LDL-cholesterol <130 mg/dL) receiving antiretroviral therapy...
June 13, 2018: Clinical Gastroenterology and Hepatology
Yasmin Abo-Zeid, Richard A Urbanowicz, Brian J Thomson, William L Irving, Alexander W Tarr, Martin C Garnett
Virus infections cause diseases of different severity ranged from mild infection e.g. common cold into life threating diseases e.g. Human Immunodeficiency virus (HIV), Hepatitis B. Virus infections represent 44% of newly emerging infections. Although there are many efficient antiviral agents, they still have drawbacks due to accumulation at off target organs and developing of virus resistance due to virus mutation. Therefore, developing a delivery system that can selectively target drug into affected organs and avoid off target accumulation would be a highly advantageous strategy to improve antiviral therapy...
June 13, 2018: International Journal of Pharmaceutics
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