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integrase inhibitor

Lise Cuzin, Pascal Pugliese, Christine Katlama, Firouzé Bani-Sadr, Tristan Ferry, David Rey, Jeremy Lourenco, Sylvie Bregigeon, Clotilde Allavena, Jacques Reynes, André Cabié
Objectives: To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs). Methods: Patients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients' characteristics related to discontinuation due to NPAEs were sought...
December 6, 2018: Journal of Antimicrobial Chemotherapy
Hotma Martogi Lorensi Hutapea, Yustinus Maladan, Widodo
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. The goal of this study was to examine the effect of IN polymorphisms on its tertiary structure and binding affinities to INIs using computational approaches...
December 2018: Heliyon
Virginia Rasi, Mario Cortina-Borja, Helen Peters, Rebecca Sconza, Claire Thorne
BACKGROUND: The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV (MTCT) have to be carefully balanced with the risks of embryo-foetal toxicities due to foetal exposure to maternal ART.The recent report of a potential safety signal with Dolutegravir use in pregnancy and potential increased rate of neural tube defects (NTDs), has raised the question of a potential class effect for Integrase Strand Inhibitors. To contribute real-world evidence we evaluated data on pregnant women receiving Raltegravir (RAL) or Elvitegravir (EVG) in the UK and Ireland...
November 20, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Sharon Nachman, Carmelita Alvero, Hedy Teppler, Brenda Homony, Anthony J Rodgers, Bobbie L Graham, Terence Fenton, Lisa M Frenkel, Renee S Browning, Rohan Hazra, Andrew A Wiznia
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...
December 2018: Lancet HIV
Augustine S Samorlu, Kemal Yelekçi, Abdullahi Ibrahim Uba
No abstract text is available yet for this article.
December 8, 2018: Journal of Biomolecular Structure & Dynamics
Kara S McGee, Nwora Lance Okeke, Christopher B Hurt, Mehri S McKellar
Transmitted drug resistance to the integrase strand transfer inhibitor (INSTI) class of antiretrovirals is very rare. We present a case of a treatment-naive female patient with human immunodeficiency virus harboring resistance to all INSTIs, including bictegravir and dolutegravir.
November 2018: Open Forum Infectious Diseases
Cissy Kityo, Alexander J Szubert, Abraham Siika, Robert Heyderman, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Shalton Mwaringa, Anna Griffiths, Immaculate Nkanya, Sheila Kabahenda, Simon Wachira, Godfrey Musoro, Chatu Rajapakse, Timothy Etyang, James Abach, Moira J Spyer, Priscilla Wavamunno, Linda Nyondo-Mipando, Ennie Chidziva, Kusum Nathoo, Nigel Klein, James Hakim, Diana M Gibb, A Sarah Walker, Sarah L Pett
BACKGROUND: In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events...
December 2018: PLoS Medicine
Giovanni Di Perri, Andrea Calcagno, Alice Trentalange, Stefano Bonora
Treatment of HIV infection has consistently evolved in the last three decades. A steady improvement in efficacy tolerability, safety and practical aspects of treatment intake has made HIV infection much easier to manage over the long term, and in optimal treatment conditions the life expectancy of persons living with HIV infection now approaches the values of the general population. The last category of antiretrovirals to be fully developed for clinical use is the one of strand-transfer integrase inhibitors (INSTIs)...
December 4, 2018: Expert Review of Clinical Pharmacology
Andrew N Phillips, Francois Venter, Diane Havlir, Anton Pozniak, Daniel Kuritzkes, Annemarie Wensing, Jens D Lundgren, Andrea De Luca, Deenan Pillay, John Mellors, Valentina Cambiano, Loveleen Bansi-Matharu, Fumiyo Nakagawa, Thokozani Kalua, Andreas Jahn, Tsitsi Apollo, Owen Mugurungi, Polly Clayden, Ravindra K Gupta, Ruanne Barnabas, Paul Revill, Jennifer Cohn, Silvia Bertagnolio, Alexandra Calmy
BACKGROUND: The integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains...
November 29, 2018: Lancet HIV
Andrew Carr, Robyn Richardson, Zhixin Liu
BACKGROUND: We updated a prior systematic review of initial ART efficacy through Week 144. MATERIALS AND METHODS: Studies (1994-July 2017) were drawn from PubMed,, Cochrane Library, and major conferences; design, eligibility, subject and ART data were abstracted. Outcomes are expressed as group size-weighted means. Mixed-effects meta-regression was used to identify sources of efficacy heterogeneity. RESULTS: Within 354 groups (181 studies, 77,999 subjects), principal backbones were tenofovir-emtricitabine (TDF/TAF-FTC) (44...
November 19, 2018: AIDS
Kyle J Hill, Leonard C Rogers, Duncan T Njenda, Donald H Burke, Stefan G Sarafianos, Anders Sönnerborg, Ujjwal Neogi, Kamalendra Singh
The oligomerization of HIV-1 integrase onto DNA is not well understood. Here we show that HIV-1 integrase binds the DNA in a biphasic (high- and low-affinity) modes. For HIV-1 subtype B, the high-affinity mode is ∼100-fold greater than low-affinity mode (Kd.DNA = 37 and 3400 nM, respectively). The Kd.DNA values of patient-derived integrases containing subtype-specific polymorphisms were affected 2-4-fold, suggesting that polymorphisms may influence on effective-concentrations of inhibitors, since these inhibitors preferably bind to integrase-DNA complex...
November 19, 2018: AIDS
Lucas Hill, Shawn R Smith, Maile Young Karris
Modern pharmacologic management of people living with HIV involves the use of fixed dose combinations of antiretrovirals that are simple to take, well tolerated, and highly effective. Specific recent pharmacologic advancements include 1) the second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) that consistently show less side effects, high tolerability, minimal drug interactions, and rapid rates of HIV viral load decline and 2) tenofovir alafenamide, a prodrug of tenofovir that concentrates in lymphoid tissue and minimizes off target effects...
2018: HIV/AIDS: Research and Palliative Care
Lisa Hamzah, Rachael Jones, Frank A Post
PURPOSE OF THE REVIEW: To identify recent data that inform the management of individuals with HIV and chronic kidney disease. RECENT FINDINGS: Several nonnucleoside reverse transcriptase, protease, and integrase strand transfer inhibitors inhibit tubular creatinine secretion resulting in stable reductions in creatinine clearance of 5-20 ml/min in the absence of other manifestations of kidney injury. Progressive renal tubular dysfunction is observed with tenofovir disoproxil fumarate in clinical trials, and more rapid decline in estimated glomerular filtration rate in cohort studies of tenofovir disoproxil fumarate and atazanavir, with stabilization, improvement or recovery of kidney function upon discontinuation...
November 15, 2018: Current Opinion in Infectious Diseases
S Modica, B Rossetti, F Lombardi, F Lagi, M Maffeo, R D'Autilia, M Pecorari, I Vicenti, B Bruzzone, G Magnani, S Paolucci, D Francisci, G Penco, D Sacchini, M Zazzi, A De Luca, A Di Biagio
OBJECTIVES: The aim of the study was to analyse the prevalence of integrase resistance mutations in integrase strand transfer inhibitor (INSTI)-experienced HIV-1-infected patients and its predictors. METHODS: We selected HIV-1 integrase sequences from the Antiviral Response Cohort Analysis (ARCA) database, derived from INSTI-experienced patients between 2008 and 2017. Differences in the prevalence of resistance to raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG) were assessed by χ2 test and predictors of resistance were analysed by logistic regression...
November 21, 2018: HIV Medicine
Emma D Deeks
Bictegravir is a new integrase strand transfer inhibitor (INSTI) with a high genetic barrier to the development of HIV-1 resistance. The drug is co-formulated with the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (AF) in a single-tablet regimen (STR) for the once-daily treatment of HIV-1 infection in adults (bictegravir/emtricitabine/tenofovir AF; Biktarvy® ). In phase 3 trials, bictegravir/emtricitabine/tenofovir AF was noninferior to dolutegravir-based therapy (dolutegravir/abacavir/lamivudine or dolutegravir plus emtricitabine/tenofovir AF) in establishing virological suppression in treatment-naïve adults through 96 weeks' treatment and, similarly, was noninferior to ongoing dolutegravir/abacavir/lamivudine or boosted elvitegravir- or protease inhibitor (PI)-based therapy in preventing virological rebound over 48 weeks in treatment-experienced patients...
November 20, 2018: Drugs
Cecilia M Shikuma, Lindsay Kohorn, Robert Paul, Dominic C Chow, Kalpana J Kallianpur, Maegen Walker, Scott Souza, Louie Mar A Gangcuangco, Beau K Nakamoto, Francis D Pien, Timothy Duerler, Linda Castro, Lorna Nagamine, Bruce Soll
The antiretroviral drug efavirenz (EFV) has been linked to disordered sleep and cognitive abnormalities. We examined sleep and cognitive function and subsequent changes following switch to an alternative integrase inhibitor-based regimen. Thirty-two HIV-infected individuals on EFV, emtricitabine, and tenofovir (EFV/FTC/TDF) without traditional risk factors for obstructive sleep apnea (OSA) were randomized 2:1 to switch to elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) or to continue EFV/FTC/TDF therapy for 12 weeks...
November 19, 2018: HIV Clinical Trials
Miranda I Murray, Martin Markowitz, Ian Frank, Robert M Grant, Kenneth H Mayer, Krischan J Hudson, Britt S Stancil, Susan L Ford, Parul Patel, Alex R Rinehart, William R Spreen, David A Margolis
BACKGROUND: Cabotegravir (GSK1265744) is an integrase strand transfer inhibitor in development as a long-acting (LA) intramuscular injectable suspension for HIV-1 pre-exposure prophylaxis (PrEP). OBJECTIVE: We report participant outcomes from the phase IIa ECLAIR study related to tolerability, acceptability, and satisfaction of cabotegravir LA. METHODS: The ECLAIR study ( identifier, NCT02076178) was a randomized, placebo-controlled study in healthy men not at high risk of acquiring HIV-1...
November 16, 2018: HIV Clinical Trials
Ofentse Nobela, Ryan S Renslow, Dennis G Thomas, Sean M Colby, Sanyasi Sitha, Patrick Berka Njobeh, Louis du Preez, Fidele Tugizimana, Ntakadzeni Edwin Madala
Plants from the Asteraceae family are known to contain a wide spectrum of phytochemicals with various nutraceutical properties. One important phytochemical, chicoric acid (CA), is reported to exist in plants, such as Sonchus oleraceus and Bidens pilosa, as stereoisomers. These CA molecules occur either as the naturally abundant RR-chicoric acid (RR-CA), or the less abundant RS-chicoric acid (RS-CA), also known as meso-chicoric acid. To date, little is known about the biological activity of RS-CA, but there is evidence of its anti-human immunodeficiency virus (HIV) properties...
November 2, 2018: Journal of Photochemistry and Photobiology. B, Biology
Eungi Choi, Jayapal Reddy Mallareddy, Dai Lu, Srikanth Kolluru
AIDS caused by the infection of HIV is a prevalent problem today. Rapid development of drug resistance to existing drug classes has called for the discovery of new targets. Within the three major enzymes (i.e., HIV-1 protease, HIV-1 reverse transcriptase and HIV-1 integrase [IN]) of the viral replication cycle, HIV-1 IN has been of particular interest due to the absence of human cellular homolog. HIV-1 IN catalyzes the integration of viral genetic material with the host genome, a key step in the viral replication process...
October 2018: Future Science OA
Karen Jacobson, Onyema Ogbuagu
The integrase strand transfer inhibitor (INSTI) class of antiretroviral therapy (ART) may result in faster time to virologic suppression compared with regimens that contain protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, differences in time to achieve virologic suppression are not well-defined in routine clinical settings with contemporary antiretroviral agents.Study was a retrospective single-center study of treatment-naïve human immunodeficiency virus (HIV) patients initiating ART between 2013 and 2016...
October 2018: Medicine (Baltimore)
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