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Biochim Biophys Acta Biomembr 2018 Dec 11. Epub 2018 Dec 11.

Forschungszentrum Jülich GmbH, Jülich Centre for Neutron Science at SNS, Oak Ridge National Laboratory, Oak Ridge, TN 37831, United States of America.

A short sequence on the gp41 envelope protein of HIV-1 is integral to infection by the virus. Without this sequence, termed the fusion peptide (FP), the virus is far less effective at fusing with the cellular membrane. One of the interesting features of the isolated FP is that it transitions between an α-helical conformation and a β-sheet conformation in lipid bilayer membranes as a function of lipid composition and concentration, and the transition correlates with fusion. Read More

J Acquir Immune Defic Syndr 2018 Dec 6. Epub 2018 Dec 6.

AIDS Clinical Center and.

Background: Acute hepatitis C virus (HCV) infection is increasing among HIV-1-infected individuals in Tokyo. Appropriate clinical management is needed.

Setting: To delineate the epidemiological status of HCV transmission, we analyzed stocked plasma samples of HCV/HIV-1-coinfected patients seen at the largest referral center for HIV care in Tokyo. Read More

J Med Virol 2018 Dec 13. Epub 2018 Dec 13.

Gilead Sciences, Inc., Foster City, CA, USA.

An HIV-1 integrase (IN) genotyping assay was developed to evaluate clinical samples from patients infected with HIV-1 subtype AE, a subtype highly prevalent in Asia. The HIV-1 integrase gene was amplified from plasma-derived HIV-1 viral RNA via RT-PCR followed by population sequencing. Assay sensitivity was also evaluated using serially diluted plasma samples. Read More

AIDS Rev 2018 ;20(4):220-225

Department of Neuroscience, Center for Translational AIDS Research, Philadelphia, USA.

Here, we review the progress that has been made in achieving a cure of HIV-1 infection. To date, this has only occurred in one person after he received allogeneic stem cell transplants from a CCR5 ∆32 homozygous donor in addition to chemotherapy and radiation to treat his acute myelocytic leukemia. The general consensus is that achieving a sustained remission of infection in the absence of antiretroviral therapy will involve a combination of strategies that involve both the targeting of the latent proviral genome and the induction of more effective anti-HIV-1 immune responses. Read More

Mol Ther Methods Clin Dev 2019 Mar 26;12:32-46. Epub 2018 Oct 26.

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Focusing T cell responses on the most vulnerable parts of HIV-1, the functionally conserved regions of HIV-1 proteins, is likely a key prerequisite for vaccine success. For a T cell vaccine to efficiently control HIV-1 replication, the vaccine-elicited individual CD8 T cells and as a population have to display a number of critical traits. If any one of these traits is suboptimal, the vaccine is likely to fail. Read More

Nat Commun 2018 Dec 13;9(1):5305. Epub 2018 Dec 13.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, HIV-1 establishes proviruses in long-lived CD4 memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Here we show that the HIV-1 provirus activates innate immune signaling in isolated dendritic cells, macrophages, and CD4 T cells. Read More

Enferm Infecc Microbiol Clin 2018 Dec;36 Suppl 2:3-9

Servicio de Enfermedades Infecciosas, Fundación Lucha contra el Sida, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España. Electronic address:

Darunavir is the gold standard protease inhibitor in antiretroviral treatment. It has undergone complete development through randomised clinical trials throughout the entire spectrum of HIV infection, with 2 different dosages and clear indications of when to use each one of them. It has been studied in mono, dual and triple therapy. Read More

Enferm Infecc Microbiol Clin 2018 Dec;36 Suppl 2:10-16

Servicio de Enfermedades Infecciosas, Hospital Universitari Vall d'Hebron, Barcelona; Vall d'Hebron Institut de Recerca, Barcelona.

Symtuza is the first and only treatment for HIV-1 that combines 2 nucleos(t)ide analogues (emtricitabine and tenofovir alafenamide) together with a boosted protease inhibitor (darunavir/cobicistat) in a once-daily single tablet regimen (STR). This combination is active against a wide variety of HIV strains and, in turn, avoids bone and renal toxicity associated with the use of tenofovir disoproxil fumarate, combining efficacy, convenience, tolerability and high genetic barrier. Pharmacokinetic studies of its components show a favourable profile, allowing its use in a wide variety of patients and clinical situations. Read More

Viruses 2018 Dec 12;10(12). Epub 2018 Dec 12.

Institute of Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.

As part of the Pr55 polyprotein, p6 fulfills an essential role in the late steps of the replication cycle. However, almost nothing is known about the functions of the mature HIV-1 p6 protein. Recently, we showed that p6 is a bona fide substrate of the insulin-degrading enzyme (IDE), a ubiquitously expressed zinc metalloprotease. Read More

J Antimicrob Chemother 2018 Dec 13. Epub 2018 Dec 13.

Institute for Global Health, University College London, London, UK.

Objectives: In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data. Read More

ACS Infect Dis 2018 Dec 13. Epub 2018 Dec 13.

HIV-1 protease is one of the prime targets of agents used in antiretroviral therapy against HIV. However, under selective pressure of protease inhibitors, primary mutations at the active site weaken inhibitor binding to confer resistance. Darunavir (DRV) is the most potent HIV-1 protease inhibitor in clinic; resistance is limited, as DRV fits well within the substrate envelope. Read More

Curr HIV Res 2018 Dec 12. Epub 2018 Dec 12.

Y. R. Gaitonde Centre for AIDS Research and Education, VHS Hospital Campus, Taramani, Chennai. India.

Background: Anti-viral cytokine expressions by cytotoxic T-cells and lower activation rates have been reported to correlate with suppressed HIV replication in long-term non-progressors (LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1 subtype and geographical locations.

Objective: This study evaluates cytokine expression and T-cells activation in relation to disease non-progression in LTNP. Read More

Nature 2018 Dec 12. Epub 2018 Dec 12.

Division of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160) cleaved to (gp120 and gp41), interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse viral and target-cell membranes. The gp120-coreceptor interaction has previously been proposed as the most crucial trigger for unleashing the fusogenic potential of gp41. Here we report a cryo-electron microscopy structure of a full-length gp120 in complex with soluble CD4 and unmodified human CCR5, at 3. Read More

Sci Rep 2018 Dec 12;8(1):17794. Epub 2018 Dec 12.

Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.

HIV-associated neurocognitive disorders (HAND) are frequently associated with impaired executive function and verbal fluency. Given limited knowledge concerning HAND in Sub-Saharan-Africa and lack of Cameroonian adult neuropsychological (NP) test norms, we administered four executive function [Halstead Category Test (HCT), Wisconsin Card Sorting Test (WCST), Color Trails-II (CTT2), and Stroop Color-Word-Interference (SCWT)] and three verbal fluency (Category, Action, and Letter Fluency) tests to 742 adult Cameroonians (395 HIV-, 347 HIV+). We developed demographically-corrected NP test norms and examined the effects of HIV and related variables on subjects' executive function and verbal fluency. Read More

J Virol 2018 Dec 12. Epub 2018 Dec 12.

Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA

Prevention of mother to child transmission (MTCT) is an indispensable component of the combat against the global AIDS epidemic. A combination of passive broadly neutralizing antibody (bnAb) infusion and active vaccination promises to provide protection of infants against MTCT from birth through the breastfeeding period, and could prime the immune system for life-long immunity. In this study, we investigate the impact of a single infusion of CD4 binding site (CD4bs) bnAb administered at birth on antibody responses elicited by concurrent active HIV envelope vaccination. Read More

J Virol 2018 Dec 12. Epub 2018 Dec 12.

Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.

Eliciting highly functional CD8 cytotoxic T lymphocyte (CTL) responses against a broad range of epitopes will likely be required for immunotherapeutic control of HIV-1 infection. However, the combination of CTL exhaustion and the ability of HIV-1 to rapidly establish CTL escape variants represent major hurdles towards this goal. Our previous work highlighted the use of monocyte derived, mature, high IL-12-producing type-1 polarized dendritic cells (MDC1) to selectively induce more potent effector CTLs derived from naïve, rather than memory, CD8 T cell precursors isolated from HIV-1 positive participants in the Multicenter AIDS Cohort Study. Read More

J Virol 2018 Dec 12. Epub 2018 Dec 12.

Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, Florida, USA

Broadly neutralizing antibodies (bNAbs) target five major epitopes on the HIV-1 envelope glycoprotein (Env). The most potent bNAbs have median IC values in the nanomolar range and the broadest bNAbs neutralize up to 98% of HIV-1 strains. The engineered HIV-1 entry inhibitor eCD4-Ig has greater breadth than and similar potency to bNAbs. Read More

Retrovirology 2018 Dec 12;15(1):76. Epub 2018 Dec 12.

Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz -IOC, FIOCRUZ, Av Brasil, 4365, Pavilhão Leônidas Deane, sala 401, Rio de Janeiro, 21040360, Brazil.

Objectives: To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection.

Methods: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8CD38HLA-DR T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Read More

Turk J Med Sci 2018 12 12;48(6):1129-1134. Epub 2018 Dec 12.

Public Health General Directorate, Ministry of Health, Ankara, Turkey

Background/aim: Limited data on syphilis coinfection in human immunodeficiency virus (HIV) positive cases exist in Turkey. Our aim is to investigate syphilis coinfection and to evaluate the compatibility of the screening Architect Syphilis Tp ELISA with the fluorescent treponemal antibody absorption (FTA-abs) confirmation test in HIV positive cases.

Materials And Methods: Totally 519 HIV positive patients were included in the study. Read More

Front Immunol 2018 21;9:2686. Epub 2018 Nov 21.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, China.

Persistent inflammation and extensive immune activation have been associated with HIV-1/SIV pathogenesis. Previously, we reported that cholesterol-25-hydroxylase (CH25H) and its metabolite 25-hydroxycholesterol (25-HC) had a broad antiviral activity in inhibiting Zika, Ebola, and HIV-1 infection. However, the underlying immunological mechanism of CH25H and 25-HC in inhibiting viral infection remains poorly understood. Read More

Front Microbiol 2018 21;9:2738. Epub 2018 Nov 21.

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

Proteasomal degradation pathways play a central role in regulating a variety of protein functions by controlling not only their turnover but also the physiological behavior of the cell. This makes it an attractive target for the pathogens, especially viruses which rely on the host cellular machinery for their propagation and pathogenesis. Viruses have evolutionarily developed various strategies to manipulate the host proteasomal machinery thereby creating a cellular environment favorable for their own survival and replication. Read More

Front Behav Neurosci 2018 22;12:285. Epub 2018 Nov 22.

Department of Psychology, Program in Behavioral Neuroscience, University of South Carolina, Columbia, SC, United States.

Frontal-subcortical circuit dysfunction is commonly associated with apathy, a neuropsychiatric sequelae of human immunodeficiency virus type-1 (HIV-1). Behavioral and neurochemical indices of apathy in the nucleus accumbens (NAc), a key brain region involved in frontal-subcortical circuitry, are influenced by the factor of biological sex. Despite evidence of sex differences in HIV-1, the effect of biological sex on medium spiny neurons (MSNs), which are central integrators of frontal-subcortical input, has not been systematically evaluated. Read More

Cancer Treat Res 2019 ;177:211-229

Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.

Merkel cell carcinoma (MCC) is a highly aggressive, primary neuroendocrine cancer of the skin. The majority of MCC cases are associated with the recently discovered Merkel cell polyomavirus (MCPyV), while the remaining are caused by ultraviolet (UV) light-induced mutations from excessive sunlight exposure. The risk of developing MCC is much higher in the white population relative to all other races. Read More

Immunobiology 2018 Nov 28. Epub 2018 Nov 28.

Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy; Infectious Diseases Unit, Sapienza University, Santa Maria Goretti Hospital, Via Canova, 04100, Latina, Italy.

HIV infection is characterized by a state of chronic activation of the immune system, which is not completely reversed by antiretroviral treatment (ART). The aim of this study was to assess myeloid and lymphoid activation markers during HIV infection, before and one year after ART initiation, in AIDS and non-AIDS presenters. Treatment naïve HIV positive patients were enrolled in this study. Read More

Zhonghua Yu Fang Yi Xue Za Zhi 2018 Dec;52(12):1259-1263

Department of AIDS Prevention and Control, Shandong Provincial Center for Disease Control and Prevention, Jinan 250014, China.

To describe the confirmation process and long-term follow-up results of 1 case of HIV with long term progression. The subject was a HIV infected man aged 27 years old. The first HIV antibody positive was detected by ELISA in August 7(th), 2013. Read More

Cell Rep 2018 Dec;25(11):3123-3135.e6

National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban 4041, South Africa. Electronic address:

Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif. Read More

Virus Evol 2018 Jul 4;4(2):vey030. Epub 2018 Dec 4.

Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, USA.

Understanding genetic variation in human immunodeficiency virus (HIV) is clinically and immunologically important for patient treatment and vaccine development. We investigated the longitudinal intra-host genetic variation of HIV in over 3,000 individuals in the US National HIV Surveillance System with at least four reported HIV-1 polymerase () sequences. In this population, we identified 149 putative instances of superinfection (i. Read More

Front Immunol 2018 27;9:2755. Epub 2018 Nov 27.

Department of Hematology, Rheumatology and Infectious Disease, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Costimulatory and coinhibitory receptors play a key role in regulating immune responses to infection and cancer. Coinhibitory receptors include programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin and ITIM domain (TIGIT), which suppress immune responses. Coinhibitory receptors are highly expressed on exhausted virus-specific T cells, indicating that viruses evade host immune responses through enhanced expression of these molecules. Read More

MBio 2018 Dec 11;9(6). Epub 2018 Dec 11.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA

The human immunodeficiency virus type 1 (HIV-1) envelope (Env) trimer evades antibody recognition by adopting a closed prefusion conformation. Here, we show that two conserved tyrosines (Y173, Y177) within the second variable (V2) loop of the gp120 Env glycoprotein are key regulators of the closed, antibody-protected state of the trimer by establishing intramolecular interaction with the base of the third variable (V3) loop. Mutation of Y177 and/or Y173 to phenylalanine or alanine dramatically altered the susceptibility of diverse HIV-1 strains to neutralization, increasing sensitivity to weakly and nonneutralizing antibodies directed against diverse Env regions, consistent with the adoption of an open trimer configuration. Read More

Anal Chem 2018 Dec 11. Epub 2018 Dec 11.

In this study, we present a simple, hand-powered, and electricity-free centrifuge platform based on a commercially available "fidget-spinner." The centrifugal force provided by this inexpensive and easy-to-use toy is sufficient to separate whole blood, producing a plasma yield rate and purity of 30% and 99%, respectively, separated in as little as 4-7 minutes. We verified the separated plasma by performing a paper-based HIV-1 p24 capsid protein enzyme-linked immunosorbent assay, which achieved a recovery rate of up to 98%, indicating the plasma features extremely low matrix interference effects. Read More

J Antimicrob Chemother 2018 Dec 6. Epub 2018 Dec 6.

INSERM U1043 - CNRS UMR5282 - Toulouse University Paul Sabatier, CPTP, Toulouse, France.

Objectives: To determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen.

Patients And Methods: Four hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. Read More

Clin Infect Dis 2018 Dec 11. Epub 2018 Dec 11.

Institute for Global Health, University College London, London, UK.

Background: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired HIV-1 can be transmitted, generated de novo through virus replication, or technical errors. The first are likely to persist and result in treatment failure while the latter two could be stochastic and transient.

Methods: Ultra-deep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the UK was performed to detect DRMinVs at mutation frequency between 2-20%. Read More

Heliyon 2018 Dec 1;4(12):e00956. Epub 2018 Dec 1.

Biology Department, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.

Integrase (IN) plays an essential role in HIV-1 replication, by mediating integration of the viral genome into the host cell genome. IN is a potential target of antiretroviral (ARV) therapeutic drugs such as ALLINI, Raltegravir (RAL), and Elvitegravir (EVG). The effect of IN polymorphisms on its structure and binding affinity to the integrase inhibitors (INIs) is not well understood. Read More

Front Immunol 2018 26;9:2735. Epub 2018 Nov 26.

Department of Pathology, New York University School of Medicine, New York, NY, United States.

Disease progression among HIV-1-infected individuals varies widely, but the mechanisms underlying this variability remains unknown. Distinct disease outcomes are the consequences of many factors working in concert, including innate and adaptive immune responses, cell-mediated and humoral immunity, and both genetic and phenotypic factors. Current data suggest that these multifaceted aspects in infected individuals should be considered as a whole, rather than as separate unique elements, and that analyses must be performed in greater detail in order to meet the requirements of personalized medicine and guide optimal vaccine design. Read More

Front Immunol 2018 23;9:2719. Epub 2018 Nov 23.

Program in Cellular and Molecular Medicine, Department of Pediatrics, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States.

The importance of myeloid cells in HIV transmission in the female genital tract is uncertain. Because it is difficult to study the early events in HIV transmission in humans, most of our knowledge is based on animal models of SIV infection in Rhesus macaques and more recently HIV infection in humanized mice. However, these models may not accurately recapitulate transmission in the human genital tract. Read More

Int J Nanomedicine 2018 15;13:7441-7455. Epub 2018 Nov 15.

Laboratory of Experimental Surgical Oncology, Section of Surgical Oncology, Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands,

Introduction: PEGylated liposomes are widely used and studied as carriers for chemotherapeutics. While pharmacokinetics of the encapsulated drug is drastically altered resulting in favorable circulation time, improved tumor accumulation, and better manageable or reduced side effects, therapeutic efficacy has been disappointing. Major drawbacks are a failure to reach the tumor cell, limited penetration depth, and impaired uptake by tumor cells. Read More

J Acquir Immune Defic Syndr 2018 Dec 3. Epub 2018 Dec 3.

Academic Medical Center of the University of Amsterdam, Amsterdam, the Netherlands.

Background: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV uninfected individuals more likely and whether restoration depends on gender, age and other individual characteristics.

Methods: We determined median and quartile reference values for CD4 and CD8 cell count and their ratio using cross-sectional data from 2,309 HIV-negative individuals. Read More

AIDS 2018 Nov 27. Epub 2018 Nov 27.

Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.

No consensus has been reached on how to define cerebrospinal fluid HIV-1 escape (CSF-E). We describe its prevalence in 1095 paired CSF-plasma HIV-RNA measurements from antiretroviral-treated patients according to several definitions and neurological affections. CSF-E prevalence varied substantially (9. Read More

AIDS 2018 Nov 27. Epub 2018 Nov 27.

Laboratório de AIDS & Imunologia Molecular. Instituto Oswaldo Cruz (IOC) - FIOCRUZ. Rio de Janeiro, Brazil.

Objective: To investigate the impact of intersubtype HIV-1 superinfection (SI) on viremia, reservoir reseeding, viral evolution, and disease progression in HIV controllers (HIC).

Design: Longitudinal analysis of two Brazilian HIC subjects (EEC09 and VC32) previously identified as dually infected with subtypes B and F1 viruses.

Methods: Changes in plasma viremia, total HIV-1 DNA levels, CD4 T cell counts and HIV-1 quasispecies composition were measured over time. Read More

AIDS 2018 Nov 27. Epub 2018 Nov 27.

San Francisco Veterans Affairs (VA) Medical Center and University of California San Francisco (UCSF), 4150 Clement Street, 111W, San Francisco, CA 94121, USA.

Objectives: Reversing HIV-1 latency has been suggested as a strategy to eradicate HIV-1. We investigated the effect of romidepsin on the HIV transcription profile in participants from the REDUC part B clinical trial.

Design: Seventeen participants on suppressive antiretroviral therapy were vaccinated with six doses of the therapeutic vaccine Vacc-4x followed by treatment with three doses of romidepsin. Read More

Curr Opin HIV AIDS 2018 Dec 10. Epub 2018 Dec 10.

Chan Zuckerberg Biohub, San Francisco, California, USA.

Purpose Of Review: To provide a summary of the recent data examining infected CD4+ T cell dynamics during ART and implications for cure strategies.

Recent Findings: HIV-1 cure is a worldwide unmet medical need. Although combination antiretroviral therapies effectively suppress HIV-1 replication in vivo, viral rebound occurs shortly after therapy cessation. Read More

Blood Adv 2018 Dec;2(23):3479-3482

Department of Medicine, University of California San Francisco, San Francisco, CA.

Proc Natl Acad Sci U S A 2018 Dec 10. Epub 2018 Dec 10.

Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908;

HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. Read More

J Immunol 2018 Dec 10. Epub 2018 Dec 10.

Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824;

Current advances in combined antiretroviral therapy have rendered HIV infection a chronic, manageable disease; however, the problem of persistent immune activation still remains despite treatment. The immune cell receptor SLAMF7 has been shown to be upregulated in diseases characterized by chronic immune activation. In this study, we studied the function of the SLAMF7 receptor in immune cells of HIV patients and the impacts of SLAMF7 signaling on peripheral immune activation. Read More

J Clin Virol 2018 Dec 3;110:36-41. Epub 2018 Dec 3.

Université Paris Descartes, EA 7327, Sorbonne Paris Cité, AP-HP, Laboratoire de Virologie, Hôpital Necker, Paris, France. Electronic address:

Background: HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART).

Objectives: The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France.

Study Design: The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1. Read More

Int J Biol Macromol 2018 Dec 7. Epub 2018 Dec 7.

Institute of Nano Electronic Engineering, Universiti Malaysia Perlis, Kangar 01000, Perlis, Malaysia; School of Microelectronic Engineering, Universiti Malaysia Perlis, 02600 Arau, Pauh putra, Perlis, Malaysia.

Interaction between split RNA aptamer and the clinically important target, HIV-1 Tat was investigated on a biosensing surface transduced by functionally choreographed multiwall carbon nanotubes (MWCNTs). Acid oxidation was performed to functionalize MWCNTs with carboxyl functional groups. X-ray photoelectron spectroscopy analysis had profound ~2. Read More

Int J Infect Dis 2018 Oct 25. Epub 2018 Oct 25.

MSD Lda, Quinta da Fonte, Edifício Vasco da Gama 19, 2770-192 Paço de Arcos, Portugal. Electronic address:

Objectives: To characterize the profile of NARC in older HIV-1-infected population and explore the factors associated with multiple NARC.

Methods: Multicenter, cross-sectional study including HIV-1-infected patients ≥50 years, virologically suppressed and on a stable ART regimen for at least 6 months. Multiple regression model explored the association of demographic and clinical variables with the number of NARC. Read More

Biochem Pharmacol 2018 Dec 6. Epub 2018 Dec 6.

University of Strasbourg, EA7292, DHPI, IUT Louis Pasteur, Schiltigheim, France. Electronic address:

The DNA-PK complex is the major component of the predominant mechanism of DSB repair in humans. In addition, this complex is involved in many other processes such as DNA recombination, genome maintenance, apoptosis and transcription regulation. Several studies have linked the decrease of the DNA-PK activity with cancer initiation, due to defects in the repair. Read More

Ultramicroscopy 2018 Nov 29. Epub 2018 Nov 29.

Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA. Electronic address:

Single-particle electron cryo-microscopy and computational image classification can be used to analyze structural variability in macromolecules and their assemblies. In some cases, a particle may contain different regions that each display a range of distinct conformations. We have developed strategies, implemented within the Frealign and cisTEM image processing packages, to focus-classify on specific regions of a particle and detect potential covariance. Read More

Lancet HIV 2018 Dec;5(12):e715-e722

Department of Pediatrics, Jacobi Medical Center, New York, NY, USA.

Background: Raltegravir is an integrase inhibitor approved for use in adults and children with HIV-1 infection, but there are no data on the long-term use of this medication in children. We aimed to assess the long-term safety, tolerability, pharmacokinetics, and efficacy of multiple raltegravir formulations in children aged 4 weeks to 18 years with HIV-1 infection.

Methods: In this phase 1/2 open-label multicentre trial (IMPAACT P1066), done in 43 IMPAACT network sites in the USA, South Africa, Brazil, Botswana, and Argentina, eligible participants were children aged 4 weeks to 18 years with HIV-1 infection who had previously received antiretroviral therapy (ART), had HIV-1 RNA higher than 1000 copies per mL, and no exposure to integrase inhibitors. Read More