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Bioorg Chem 2019 Feb 8;86:437-444. Epub 2019 Feb 8.

Department of Chemistry, Dnyanopasak College, Parbhani 431 401, MS, India. Electronic address:

A series of pyrazolo[3.4,d]thiazole hybrids 6 were synthesized from 5-arylidene-2-imino-3-(4-arylthiazol-2-yl)-thiazolidin-4-ones 5. The 5-arylidene-2-imino-3-(4-arylthiazol-2-yl)-thiazolidin-4-ones 5 were synthesized from 2-amino-4-arylthiazoles 1 and 2-chloro-acetamido-4-arylthiazoles 2 via the formation of 2-imino-3-(4-substituted-arylthiazol-2-yl)-thiazolidin-4-ones 3 using substituted aldehydes 4. Read More

Nat Commun 2019 Feb 15;10(1):763. Epub 2019 Feb 15.

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.

The N-terminal fusion peptide (FP) of the human immunodeficiency virus (HIV)-1 envelope glycoprotein (Env) gp41 subunit plays a critical role in cell entry. However, capturing the structural flexibility in the unbound FP is challenging in the native Env trimer. Here, FP conformational isomerism is observed in two crystal structures of a soluble clade B transmitted/founder virus B41 SOSIP. Read More

EBioMedicine 2019 Feb 12. Epub 2019 Feb 12.

HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium. Electronic address:

Viruses 2019 Feb 15;11(2). Epub 2019 Feb 15.

Division of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

A chimeric vesicular stomatitis virus with the glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, is a potent viral vaccine vector that overcomes several of the limitations of wild-type VSV. Here, we evaluated the potential of VSV-GP as an HIV vaccine vector. We introduced genes for different variants of the HIV-1 envelope protein Env, i. Read More

Int J Antimicrob Agents 2019 Feb 12. Epub 2019 Feb 12.

Clinical Department, Istituto Nazionale per le Malattie infettive "Lazzaro Spallanzani", IRCCS, Rome, Italy.

Introduction: Our aim was to investigate the prevalence of DOR resistance mutations in NNRTI experienced patients.

Methods: DOR resistance was assessed in samples from patients NNRTI-experienced who underwent genotypic test for virologic failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, K103N plus P225H. Read More

J Int AIDS Soc 2019 Feb;22(2):e25250

Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Introduction: Discontinuations of HIV preexposure prophylaxis (PrEP) by at-risk individuals could decrease the effectiveness of PrEP. Our objective was to characterize patterns of, reasons for, and clinical outcomes associated with PrEP discontinuations in primary care.

Methods: We conducted medical chart reviews for patients prescribed PrEP during 2011 to 2014 at a Boston community health centre specializing in healthcare for sexual and gender minorities. Read More

J Acquir Immune Defic Syndr 2019 Feb 7. Epub 2019 Feb 7.

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.

Background: Unique recombinant forms (URFs) were generated in dually-infected or multiply-infected individuals, and some of URFs can be transmitted to many people resulting in the emergence of circulating recombinant forms (CRFs). We examined whether there was evidence for onward transmission of multiple URFs among men who have sex with men (MSM) in Beijing.

Methods: A total of 146 MSM subjects with acute/early HIV-1 infection were recruited from the Beijing PRIMO clinical cohort between September 2010 and July 2012. Read More

J Acquir Immune Defic Syndr 2019 Feb 7. Epub 2019 Feb 7.

Department of Psychology, Indiana University-Purdue University Indianapolis (IUPUI), Indianapolis, Indiana.

Background: Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown.

Methods: Using the Veterans Aging Cohort Study-Survey Cohort, insomnia symptoms were measured and dummy coded with the item, "Difficulty falling or staying asleep?" (5-point scale from no difficulty to bothers a lot). Read More

J Acquir Immune Defic Syndr 2019 Feb 7. Epub 2019 Feb 7.

Service of Molecular Virology, Institut de Biologie et de Médecine Moléculaires (IBMM), Université Libre de Bruxelles (ULB), Gosselies, Belgium.

Objectives: Few single latency-reversing agents (LRAs) have been tested in vivo and only some of them have demonstrated an effect, albeit weak, on the decrease of latent reservoir. Therefore, other LRAs and combinations of LRAs need to be assessed. Here, we evaluated the potential of combined treatments of therapeutically promising LRAs, disulfiram and romidepsin. Read More

J Antimicrob Chemother 2019 Feb 14. Epub 2019 Feb 14.

IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France.

Objectives: To assess, at ART initiation, the impact of baseline substitutions in protease, Gag and gp41 regions on the virological response to a first-line PI-based regimen.

Patients And Methods: One hundred and fifty-four HIV-infected ART-naive patients initiating a PI-based regimen including darunavir (n = 129) or atazanavir (n = 25) were assessed, including 36 experiencing virological failure (VF). Whole pol, gag and gp41 genes were sequenced at ART baseline by ultra-deep sequencing (UDS) using Illumina® technology. Read More

Analyst 2019 Feb 15. Epub 2019 Feb 15.

Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Guangdong Institute of Eco-Environmental and Science &Technology, Guangzhou 510650, China.

In this work, a label-free fluorescence biosensor for simple detection of the HIV-1 gene was proposed by using toehold-mediated strand displacement reactions (TMSDRs) combined with a non-enzymatic target recycling amplification strategy. In this system, two TMSDRs were used. In the presence of the HIV-1 gene, an autocatalytic DNA machine can be activated. Read More

Curr HIV Res 2019 Feb 14. Epub 2019 Feb 14.

Pharmacy Department, Jos University Teaching Hospital, Jos. Nigeria.

Background: Adverse drug reactions (ADRs) associated with antiretroviral therapy (ART) can rapidly reverse the gains of ART resulting in poor health outcomes. We need an improved understanding of specific ART-related ADRs that influence virologic outcomes.

Objective: To investigate the frequency of clinical ADRs and assess their effect on virologic failure in patients on ART. Read More

Nucleic Acids Res 2019 Feb 15. Epub 2019 Feb 15.

Fundamental Microbiology and Pathogenicity Laboratory, UMR 5234 CNRS-University of Bordeaux, SFR TransBioMed. Bordeaux, France.

The integration of the retroviral genome into the chromatin of the infected cell is catalysed by the integrase (IN)•viral DNA complex (intasome). This process requires functional association between the integration complex and the nucleosomes. Direct intasome/histone contacts have been reported to modulate the interaction between the integration complex and the target DNA (tDNA). Read More

Afr Health Sci 2018 Dec;18(4):1057-1065

Virology Unit, Department of Microbiology, University of Ilorin, P.M.B 1515 Ilorin-Nigeria.

Background: Cytomegalovirus (CMV) infection is common among HIV-infected individuals. Its contribution to morbidity and mortality became more apparent following introduction of highly active anti-retroviral therapy (HAART) which improved survival among HIV-infected individuals.

Objectives: This study aimed at determining the prevalence of both active and latent CMV infections among HIV-infected individuals on HAART in Ilorin, Nigeria. Read More

Front Microbiol 2019 31;10:114. Epub 2019 Jan 31.

Virology Lab II, National Institute of Immunology, New Delhi, India.

Human Immunodeficiency Virus-1 (HIV-1) is known to induce the expression of SOCS3 which is a negative feed-back regulator of inflammatory responses. Here, we demonstrate that reactivation of latent HIV-1 leads to degradation of SOCS3 at early time points. Interestingly, SOCS3 degradation following transfection of HIV-1 RNA as well as polyIC in THP-1 cells further confirmed the role of viral RNA signaling in SOCS3 biology. Read More

Sci Rep 2019 Feb 14;9(1):2066. Epub 2019 Feb 14.

Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.

In recent years control theory has been applied to biological systems with the aim of identifying the minimum set of molecular interactions that can drive the network to a required state. However, in an intra-cellular network it is unclear how control can be achieved in practice. To address this limitation we use viral infection, specifically human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV), as a paradigm to model control of an infected cell. Read More

J Chem Theory Comput 2019 Feb 14. Epub 2019 Feb 14.

A new method termed "Relative Principal Components analysis" (RPCA) is introduced that extracts optimal relevant principal components to describe the change between two data samples representing two macroscopic states. The method is widely applicable in data-driven science. Calculating the components is based on a unified physical framework which introduces the objective function, namely the Kullback-Leibler divergence, appropriate for quantifying the change of the macroscopic state as it is effected by the microscopic features. Read More

Sex Transm Dis 2019 Feb 11. Epub 2019 Feb 11.

Centre for HIV & STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.

Background: Mycoplasma genitalium is associated with genital discharge syndrome, but limited prevalence data is available in South Africa. The prevalence rates of M. genitalium infection and HIV co-infection were determined in urogenital specimens collected from male and female patients presenting with genital discharge syndrome to a primary health care centre in Johannesburg, South Africa from 2007 through 2014. Read More

Cell Biol Int 2019 Feb 13. Epub 2019 Feb 13.

Disciplina de Infectologia, Laboratório de Retrovirologia, Universidade Federal de São Paulo, São Paulo, Brazil.

Although interleukin-24 (IL-24) has been extensively explored in the immunopathologies of autoimmune diseases, neoplasms, and infections, its role in HIV-1 infection has not been thoroughly elucidated to date. Therefore, the objective of this study was to evaluate the gene and protein expressions of IL-24 at the initial moments of HIV infection in PBMCs. Due to the pro-apoptotic role of IL-24, we evaluated the protein expression of caspase-3, as well as Annexin V/ Propidium Iodide flow cytometry and phosphorylation of ERK, which may induce an apoptotic signal block when phosphorylated. Read More

Front Immunol 2019 29;10:81. Epub 2019 Jan 29.

The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, NSW, Australia.

HIV-1 causes the loss of CD4 T cells via depletion or impairment of their production. The latter involves infection of thymocytes, but the involvement of hematopoietic CD34 cells remains unclear even though HIV-positive patients frequently manifest myelosuppression. In order to have a closer look at the impact of HIV-1 on T-lineage differentiation, this study utilized the OP9-DL1 coculture system, which supports T-lineage differentiation of human hematopoietic stem/progenitor cells. Read More

Nat Rev Microbiol 2019 Feb 13. Epub 2019 Feb 13.

Nature Reviews Microbiology, .

Nat Commun 2019 Feb 13;10(1):721. Epub 2019 Feb 13.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA.

Broadly neutralizing antibodies (bNAbs) represent a promising alternative to antiretroviral drugs for HIV-1 prevention and treatment. Selected antibodies to the CD4-binding site bolster envelope trimer binding via quaternary contacts. Here, we rationally engraft a new paratope, i. Read More

J Virol 2019 Feb 13. Epub 2019 Feb 13.

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

Human immunodeficiency virus type 1 subtype C (HIV-1C) has a natural deletion of a YPxL motif in its Gag-p6 late domain. This domain mediates the binding of Gag to host cell protein ALIX and subsequently facilitates viral budding. In a subset of HIV-1C infected individuals, the tetrapeptide insertion PYxE has been identified at the deleted YPxL motif site. Read More

J Virol 2019 Feb 13. Epub 2019 Feb 13.

Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, South Africa.

A vaccine regimen that elicits broadly neutralizing antibodies (bNAbs) is a major goal in HIV-1 vaccine research. Here we assessed the immunogenicity of the CAP256SU envelope protein delivered by modified vaccinia virus Ankara (M) and DNA (D) vaccines in different prime/boost combinations followed by a soluble protein (P) boost. The envelope protein (Env) contained a flexible, glycine linker and I559P mutation. Read More

J Virol 2019 Feb 13. Epub 2019 Feb 13.

Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX, USA

Simian-human immunodeficiency virus (SHIV) infection in rhesus macaques (RMs) resembles human immunodeficiency virus type 1 (HIV-1) infection in humans and serves as a tool to evaluate candidate AIDS vaccines. HIV-1 clade A (HIV-A) predominates in parts of Africa. We constructed an R5 clade A SHIV (SHIV-A; strain SHIV-KNH1144) carrying from a Kenyan HIV-A. Read More

BMC Infect Dis 2019 Feb 13;19(1):156. Epub 2019 Feb 13.

Department of Medicine, Queen Elizabeth Hospital, Hong Kong, SAR, People's Republic of China.

Background: HIV-associated neurocognitive disorder (HAND) remains prevalent in the era of combination antiretroviral therapy (cART). The prevalence of HAND in Hong Kong is not known.

Methods: Between 2013 and 2015, 98 treatment-naïve HIV-1-infected individuals were referred to and screened by the AIDS Clinical Service, Queen Elizabeth Hospital with (1) the International HIV Dementia Scale (IHDS), a screening tool that targets moderate to severe HAND, (2) the Montreal Cognitive Assessment (MoCA), a frequently used cognitive screening test and (3) the Patient Health Questionnare-9 (PHQ-9), a 9-item questionnaire that evaluates depression symptoms. Read More

Curr HIV Res 2019 Feb 12. Epub 2019 Feb 12.

Emory Vaccine Center, Emory University School of Medicine, Atlanta GA. United States.

Background: Mother-to-child transmission of HIV-1 occurs in a minority of HIV-infected mother-infant pairs, even without any interventions. The mechanisms that protect the majority of HIV-exposed infants from infection are unclear. T regulatory cells (Treg) have important immunomodulatory functions, but their role in the fetus as well as in mother-to-child transmission of HIV is under-studied. Read More

AIDS Care 2019 Feb 13:1-8. Epub 2019 Feb 13.

b David Geffen School of Medicine , University of California , Los Angeles.

Contraceptive adherence during acute and recent HIV-1 infection is important to maternal and child health given the elevated risk of vertical HIV-1 transmission and additional complications of pregnancy. Injectable contraception (IC) is the most common non-barrier modern contraception method used in sub-Saharan Africa (SSA). Adherence to IC after HIV-1 seroconversion is not well understood. Read More

Cancers (Basel) 2019 Feb 12;11(2). Epub 2019 Feb 12.

Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

Tamoxifen is the most widely used hormone therapy in estrogen receptor-positive (ER+) breast cancer, which accounts for approximately 70% of all breast cancers. Although patients who receive tamoxifen therapy benefit with respect to an improved overall prognosis, resistance and cancer recurrence still occur and remain important clinical challenges. A recent study identified TAR (HIV-1) RNA binding protein 2 (TARBP2) as an oncogene that promotes breast cancer metastasis. Read More

PLoS One 2019 13;14(2):e0210559. Epub 2019 Feb 13.

KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.

Background: The epidemiology of HIV-1 drug resistance (HIVDR) determined by Sanger capillary sequencing, has been widely studied. However, much less is known about HIVDR detected using next generation sequencing (NGS) methods. We aimed to determine the presence, persistence and effect of pre-treatment HIVDR variants detected using NGS in HIV-1 infected antiretroviral treatment (ART) naïve participants from rural Coastal Kenya. Read More

ACS Appl Mater Interfaces 2019 Feb 13. Epub 2019 Feb 13.

We describe the preparation and characterization of synthetic antibodies based on molecularly imprinted polymer nanoparticles (MIP-NPs), for the recognition and binding of the highly conserved and specific peptide motif SWSNKS (3S), an epitope of the envelope glycoprotein 41 (gp41) of human immunodeficiency virus type 1 (HIV-1). This motif is implicated in the decline of CD4+ T cells and leads to the deterioration of the immune system during HIV infection. Therefore, the development of MIP-NPs that can target and block the 3S peptide to prevent subsequent cascade interactions directed toward the killing of CD4+ T cells is of prime importance. Read More

J Neurovirol 2019 Feb 13. Epub 2019 Feb 13.

Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 6-119, Baltimore, MD, 21287, USA.

Despite the fact that human immunodeficiency virus type 1 (HIV-1) does not enter or replicate in neurons, its infection of a subset of resident brain glia cells (microglia and astrocytes) induces via disparate mechanisms, dysregulation of glutamate metabolism, neurotoxicity, and inflammation. Antiretroviral therapies suppress viral load, but cellular activation and release of proinflammatory factors, some of which is likely related to viral reservoirs, continue to promote a microenvironment that is injurious to neurons. However, the molecular mechanisms remain to be identified. Read More

Ann Pharmacother 2019 Feb 13:1060028019831674. Epub 2019 Feb 13.

1 Auburn University Harrison School of Pharmacy, AL, USA.

Objective: To review the efficacy and safety of dolutegravir (DTG) with rilpivirine (RPV) as a dual therapy regimen in the treatment of HIV-1 infection.

Data Sources: A literature search was performed using PubMed (1966 to January 2019) and Google Scholar (2014 to January 2019) with the search terms dolutegravir, rilpivirine, dual, and switch. Other resources included review articles and the manufacturer product label. Read More

J Chem Inf Model 2019 Feb 13. Epub 2019 Feb 13.

To perform massive-scale replica exchange molecular dynamics (REMD) simulations for calculating binding free energies of protein-ligand complexes, we implemented the asynchronous replica exchange (AsyncRE) framework of the binding energy distribution analysis method (BEDAM) in implicit solvent on the IBM World Community Grid (WCG) and optimized the simulation parameters to reduce the overhead and improve the prediction power of the WCG AsyncRE simulations. We also performed the first massive-scale binding free energy calculations using the WCG distributed computing gird and 301 ligands from the SAMPL4 challenge for large-scale binding free energy predictions of HIV-1 integrase complexes. In total there are ~10 thousand simulated complexes, ~1 million replicas, and ~2000 microseconds of aggregated MD simulations. Read More

MBio 2019 Feb 12;10(1). Epub 2019 Feb 12.

Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, New York, USA

Effective host immune responses against viral infection rely on the detection of the virus, activation of downstream signaling pathways, and the secretion of interferons (IFNs) and other cytokines. Many viruses can potently stimulate these responses, whereas the immune response against human immunodeficiency virus type 1 (HIV-1) remains relatively less well characterized. Here we show that HIV-1 infection with reporter viruses does not activate sensing pathways in cell lines and primary cells that are otherwise responsive to foreign nucleic acids. Read More

Trials 2019 Feb 12;20(1):123. Epub 2019 Feb 12.

Bandim Health Project, Bissau, Guinea-Bissau.

J Antimicrob Chemother 2019 Feb 11. Epub 2019 Feb 11.

Hopital Bichat Claude Bernard, Virology, Paris, France.

Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.

Patients And Methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Read More

J Infect Dis 2019 Feb 11. Epub 2019 Feb 11.

Magee-Womens Research Institute, Pittsburgh, PA.

Background: Genital infection with herpes simplex virus type-2 (HSV-2) is common, and increases risk of HIV transmission and acquisition. Pericoital use of tenofovir (TFV) gel provided protection from HSV-2 acquisition in the CAPRISA 004 Study.

Methods: We measured estimate of effect of vaginal TFV 1% gel in preventing HSV-2 acquisition among women in VOICE, randomized, double-blind, placebo-controlled trial assessing daily use of oral and vaginal TFV for HIV-1 pre-exposure prophylaxis. Read More

J Antimicrob Chemother 2019 Feb 11. Epub 2019 Feb 11.

Puerta de Hierro University Hospital and Research Institute, Madrid, Spain.

Background: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2.

Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Read More

Clin Infect Dis 2019 Feb 7. Epub 2019 Feb 7.

Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Background: The latent HIV-1 reservoir represents a major barrier to a cure. Based on the levels of HIV-1 DNA in naïve (TN) versus resting memory CD4+ T cells, it is widely hypothesized that the latent reservoir resides primarily within memory cells. Here, we compared virus production from TN and central memory (TCM) CD4+ T cells isolated from HIV-1-infected individuals on suppressive therapy. Read More

Bioinformatics 2019 Feb 12. Epub 2019 Feb 12.

KwaZulu-Natal Research Innovation and Sequencing Platform, University of KwaZulu-Natal, Durban, South Africa.

Motivation: Commonly, protease inhibitor failure is characterized by the development of multiple protease resistance mutations (PRMs). While the impact of PRMs on therapy failure are understood, the introduction of Gag mutations with protease remains largely unclear.

Results: Here, we utilized phylogenetic analyses and Bayesian network learning as tools to understand Gag-protease coevolution and elucidate the pathways leading to Lopinavir failure in HIV-1 subtype C infected patients. Read More

Curr Top Med Chem 2019 Feb 8. Epub 2019 Feb 8.

School of Molecular Sciences , Arizona State University. United States.

We review various mathematical and computational techniques for drug discovery exemplifying some recent works pertinent to group theory of nested structures of relevance to phylogeny, topological, computational and combinatorial methods for drug discovery for multiple viral infections. We have reviewed techniques from topology, combinatorics, graph theory and knot theory that facilitate topological and mathematical characterizations of protein-protein interactions, molecular-target interactions, proteomics, genomics and statistical data reduction procedures for a large set of starting chemicals in drug discovery. We have provided an overview of group theoretical techniques pertinent to phylogeny, protein dynamics especially in intrinsically disordered proteins, DNA base permutations and related algorithms. Read More

Int J Med Sci 2019 1;16(2):276-284. Epub 2019 Jan 1.

Department of Medicine, University of Washington, Seattle, WA USA.

Endothelial activation caused by HIV-1 infection leads to release of von Willebrand factor (VWF), which enters the circulation or attaches to vessel walls and self-assembles into strings and fibers, enabling platelet adhesion; this adhesive activity is regulated by the VWF-cleaving protease ADAMTS13. Our objective was to assess VWF adhesive activity and ADAMTS13 protease activity in HIV-1 infection. We measured levels of VWF antigen, VWF activation factor (a measure of adhesive activity), ADAMTS13 antigen, ADAMTS13 activity, and apolipoprotein A1 (which interferes with VWF self-association) in serum samples from HIV-1-infected men whose infections were acute (n=10), chronic untreated (n=10), or chronic treated (n=10), compared to uninfected controls (n=10). Read More

Antimicrob Agents Chemother 2019 Feb 11. Epub 2019 Feb 11.

Merck & Co., Inc., Kenilworth, NJ, USA.

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus 1 (HIV-1). A population pharmacokinetic (PK) model was developed for doravirine using pooled data from densely sampled Phase 1 trials and from sparsely sampled Phase 2b and Phase 3 trials evaluating doravirine administered orally as a single entity or as part of a fixed-dose combination of doravirine/lamivudine/tenofovir disoproxil fumarate. A one-compartment model with linear clearance from the central compartment adequately described the clinical PK of doravirine. Read More

BMC Infect Dis 2019 Feb 11;19(1):135. Epub 2019 Feb 11.

Department of Biochemistry and Virology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, J. M. Street, Parel, Mumbai, 400012, India.

Background: HIV-2 infection is characterised by a longer asymptomatic phase and slower AIDS progression than HIV-1 infection. Identifying unique immune signatures associated with HIV-2 pathogenesis may thus provide therapeutically useful insight into the management of HIV infection. This study examined the dynamics of the CD4T cell compartment, critical in disease progression, focussing on chronic HIV-2 and HIV-1 infected individuals at various stages of disease progression. Read More

J Biomol Struct Dyn 2019 Feb 12:1-24. Epub 2019 Feb 12.

b Division of Biochemistry and Biochemical Technology, Department of Chemistry, Faculty of Science , Chiang Mai University , 239 Huay Kaew Rd., Suthep, Muang , Chiang Mai 50200 , Thailand ;

Development of a highly accurate prediction model for protein-ligand inhibition has been a major challenge in drug discovery. Herein we describe a novel predictive model for the inhibition of HIV-1 integrase (IN)-LEDGF/p75 protein-protein interaction. The model was constructed using energy parameters approximated from molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations. Read More

Zhonghua Liu Xing Bing Xue Za Zhi 2019 Feb;40(2):196-201

School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China.

To understand the prevalence of drug resistance in treatment-naive injecting drug users (IDUs) infected with HIV-1 in Guangzhou. HIV-1 RNA were extracted from the serum specimens of the newly confirmed HIV-1 positive IDUs living in Guangzhou, being infected through injecting drug use and receiving no antiretroviral therapy at the time of confirmation during 2008-2015. Full sequence of protease (PR) gene and partial sequence of reverse transcriptase (RT) gene were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and sequenced. Read More

PLoS Pathog 2019 Feb 11;15(2):e1007588. Epub 2019 Feb 11.

[This corrects the article DOI: 10.1371/journal.ppat. Read More

Nat Rev Urol 2019 Feb 11. Epub 2019 Feb 11.

Nature Reviews Urology, .

AIDS 2019 Feb 7. Epub 2019 Feb 7.

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.

Background: Scale-up of antiretroviral therapy (ART) and introduction of treat-all strategy necessitates population-level monitoring of acquired HIV drug resistance (ADR) and pre-treatment drug resistance (PDR) mutations.

Methods: Blood samples were collected from 4,973 HIV-positive individuals residing in 30 communities across Botswana who participated in the Botswana Combination Prevention Project (BCPP) in 2013-2018. HIV sequences were obtained by long-range HIV genotyping. Read More