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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
Ruben van der Galiën, Rob Ter Heine, Rick Greupink, Stein J Schalkwijk, Antonius E van Herwaarden, Angela Colbers, David M Burger
Prevention of mother-to-child transmission of HIV and optimal maternal treatment are the most important goals of antiretroviral therapy in pregnant women with HIV. These goals may be at risk due to possible reduced exposure during pregnancy caused by physiological changes. Limited information is available on the impact of these physiological changes. This is especially true for HIV-integrase inhibitors, a relatively new class of drugs, recommended first-line agents and hence used by a large proportion of HIV-infected patients...
June 19, 2018: Clinical Pharmacokinetics
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
Sulav Duwal, Laura Dickinson, Saye Khoo, Max von Kleist
To achieve the 90-90-90 goals set by UNAIDS, the number of new HIV infections needs to decrease to approximately 500,000 by 2020. One of the 'five pillars' to achieve this goal is pre-exposure prophylaxis (PrEP). Truvada (emtricitabine-tenofovir) is currently the only medication approved for PrEP. Despite its advantages, Truvada is costly and requires individuals to adhere to the once-daily regimen. To improve PrEP, many next-generation regimen, including long-acting formulations, are currently investigated...
June 2018: PLoS Computational Biology
The Lancet
No abstract text is available yet for this article.
June 9, 2018: Lancet
Nathan Osman, Thibault Mesplède, Maureen Oliveira, Said Hassounah, Mark A Wainberg, Bluma G Brenner
OBJECTIVES: Dolutegravir (DTG) has achieved better long-term suppression of HIV-1 replication than other integrase strand transfer inhibitors (INSTIs), such as raltegravir (RAL) and elvitegravir (EVG). In in vitro drug washout experiments, we previously showed that removal of DTG from pre-treated MT-2 cells infected with wild-type (WT) HIV-1 showed slower rebound in viral replication as compared to removal of RAL. Now, we performed DTG, EVG, and RAL washout experiments to compare the recovery of viral integration and production of 2-LTR circles using WT HIV-1 clones, R263K viruses with low-level resistance to DTG, and viruses with G140S/Q148H mutations showing cross-resistance against all currently-approved INSTIs...
June 11, 2018: AIDS
Kaelo K Seatla, Ava Avalos, Sikhulile Moyo, Madisa Mine, Thabo Diphoko, Mosepele Mosepele, Tendani Gaolatlhe, Christopher F Rowley, Dinah Ramaabya, Joseph N Jarvis, Ishmael Kasvosve, Simani Gaseitsiwe
There is limited data on the effectiveness of Dolutegravir (DTG) based combination antiretroviral therapy (ART) in real life settings in southern Africa where HIV-1C predominates. We report here a patient infected with HIV-1C on DTG based ART previously exposed to raltegravir who developed multidrug resistance mutations to four ARV classes. There is need for drug resistance monitoring and clinical vigilance to ensure effectiveness of HIV treatment programmes even in the era of DTG based ART.
June 11, 2018: AIDS
Jienchi Dorward, Richard Lessells, Paul K Drain, Kogieleum Naidoo, Tulio de Oliveira, Yogan Pillay, Salim S Abdool Karim, Nigel Garrett
A new first-line antiretroviral therapy (ART) regimen containing dolutegravir is being rolled out in low-income and middle-income countries (LMICs). In studies from predominantly high-income settings, dolutegravir-based regimens had superior efficacy, tolerability, and durability compared with existing first-line regimens. However, several questions remain about the roll out of dolutegravir in LMICs, where most people with HIV are women of reproductive age, tuberculosis prevalence can be high, and access to viral load and HIV drug resistance testing is limited...
June 5, 2018: Lancet HIV
Rebecca Zash, Denise L Jacobson, Modiegi Diseko, Gloria Mayondi, Mompati Mmalane, Max Essex, Tendani Gaolethe, Chipo Petlo, Shahin Lockman, Lewis B Holmes, Joseph Makhema, Roger L Shapiro
BACKGROUND: Global rollout of dolutegravir-based antiretroviral therapy (ART) has been hampered in part by insufficient safety data in pregnancy. We compared birth outcomes among women initiating dolutegravir-based ART with those among women initiating efavirenz-based ART in pregnancy in Botswana. METHODS: In this observational study, we captured birth outcome data at eight government hospitals throughout Botswana (~45% of all deliveries in the country) in an ongoing study that started on Aug 15, 2014...
June 4, 2018: Lancet Global Health
T Nguyen, D B Fofana, M P Lê, C Charpentier, G Peytavin, M Wirden, S Lambert-Niclot, N Desire, M Grude, L Morand-Joubert, P Flandre, C Katlama, D Descamps, V Calvez, E Todesco, A G Marcelin
Background: Integrase strand transfer inhibitors (INSTIs) are recommended by international guidelines as first-line therapy in antiretroviral-naive and -experienced HIV-1-infected patients. Objectives: This study aimed at evaluating the prevalence at failure of INSTI-resistant variants and the impact of baseline minority resistant variants (MiRVs) on the virological response to an INSTI-based regimen. Methods: Samples at failure of 134 patients failing a raltegravir-containing (n = 65), an elvitegravir-containing (n = 20) or a dolutegravir-containing (n = 49) regimen were sequenced by Sanger sequencing and ultra-deep sequencing (UDS)...
June 4, 2018: Journal of Antimicrobial Chemotherapy
Zer-Ming Chuang, Tun-Chieh Chen
No abstract text is available yet for this article.
June 19, 2018: AIDS
Pierre Frange, Véronique Avettand-Fenoel, Florence Veber, Stéphane Blanche, Marie-Laure Chaix
Objectives: To describe the prevalence of transmitted drug resistance (TDR) among 84 children newly diagnosed with HIV in France in 2006-17. Methods: HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 Stanford list of mutations and the 2017 French National Agency for AIDS Research (ANRS) algorithm. A genotypic susceptibility score (GSS) was estimated for each first-line recommended ART combination. Results: Patients were mainly infected through mother-to-child transmission (MTCT) (73/84; 86...
May 29, 2018: Journal of Antimicrobial Chemotherapy
Isabelle Malet, Frédéric Subra, Clémence Richetta, Charlotte Charpentier, Gilles Collin, Diane Descamps, Vincent Calvez, Anne-Geneviève Marcelin, Olivier Delelis
No abstract text is available yet for this article.
May 29, 2018: MBio
Marieke Roskam-Kwint, Pauline Bollen, Angela Colbers, Marjolijn Duisenberg-van Essenberg, Veroniek Harbers, David Burger
Background: If HIV patients are unconscious or cannot swallow tablets for other reasons, antiretroviral medication is crushed and dissolved prior to administration. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the branded fixed-dose combination of dolutegravir/abacavir/lamivudine (Triumeq®, referred to as TRI); therefore, crushing of TRI is not recommended. Objectives: To investigate whether the TRI fixed-dose combination tablet can be crushed and combined with enteral nutrition without influencing pharmacokinetics (PK)...
May 22, 2018: Journal of Antimicrobial Chemotherapy
Paul E Sax, Edwin Dejesus, Gordon Crofoot, Douglas Ward, Paul Benson, Robin Dretler, Anthony Mills, Cynthia Brinson, Xuelian Wei, Sean E Collins, Andrew Cheng
: A phase 2, randomized, active-controlled study of initial antiretroviral therapy with bictegravir or dolutegravir in combination with emtricitabine and tenofovir alafenamide showed excellent efficacy. After 60 weeks of blinded treatment, participants switched to a single tablet regimen of bictegravir, emtricitabine and tenofovir alafenamide. Switching maintained viral suppression in all participants who chose to remain on the study through at least 12 weeks in the open-label phase, was safe and well tolerated...
May 22, 2018: AIDS
Jose L Casado, Marta Monsalvo, Aurora M Rojo, María Fontecha, Miguel A Rodriguez-Sagrado
Triple combinations of antiretroviral (ART) drugs are the standard treatment for HIV infection, but the challenges include long-term side effects, high costs, and adherence. The recent advent of potent and well tolerated ART has renewed the interest for newer ART strategies. A dual regimen with the combination of dolutegravir (DTG) and rilpivirine (RPV), two well tolerated, metabolic-friendly, and potent drugs could offer additional benefits. Areas covered: A review of recent randomized trials and observational cohorts concerning the use of a dual therapy with DTG plus RPV as a switching strategy in patients with viral suppression...
May 18, 2018: Expert Review of Clinical Pharmacology
Emilie R Elliot, Xinzhu Wang, Suveer Singh, Bryony Simmons, Jaime H Vera, Robert F Miller, Colin Fitzpatrick, Graeme Moyle, Myra McClure, Marta Boffito
Background: Demographic data show an increasingly aging HIV population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older HIV patients. We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50mg once daily in people living with HIV (PLWH) aged 60 and older. Additionally, to address the call for prospective neuropsychiatric toxicodynamic data, we evaluate changes in sleep quality and cognitive function after switching to abacavir (ABC)/lamivudine (3TC)/DTG, over 6 months in this population...
May 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Steven J Smith, Xue Zhi Zhao, Terrence R Burke, Stephen H Hughes
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. However, recent studies showed that when INSTI-experienced patients are put on a DTG-salvage therapy, they have reduced response rates...
May 16, 2018: Retrovirology
(no author information available yet)
This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017.1 The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisions. The main difference with respect to the previous document concerns recommended initial ART regimens, only three of which are maintained as preferential. All three include dolutegravir or raltegravir, together with emtricitabine/tenofovir alafenamide or abacavir/lamivudine...
May 11, 2018: Enfermedades Infecciosas y Microbiología Clínica
Robert E Ziegler, Bimbisar K Desai, Jo-Ann Jee, B Frank Gupton, Thomas D Roper, Timothy F Jamison
Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one-step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput...
June 11, 2018: Angewandte Chemie
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