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https://www.readbyqxmd.com/read/28637235/monotherapy-with-either-dolutegravir-or-raltegravir-fails-to-durably-suppress-hiv-viraemia-in-humanized-mice
#1
Alonso Heredia, Said Hassounah, Sandra Medina-Moreno, Juan C Zapata, Nhut M Le, Yingshan Han, James S Foulke, Charles Davis, Joseph Bryant, Robert R Redfield, Mark A Wainberg
Objectives: To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy. Methods: We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIV BaL . Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture...
June 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28621159/dual-antiretroviral-therapy-for-hiv-infection
#2
Vicente Soriano
For two decades' triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert Opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy...
June 16, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28590329/antiretroviral-initiation-is-associated-with-increased-skeletal-muscle-area-and-fat-content
#3
Kristine M Erlandson, Suzanne Fiorillo, Fadzai Masawi, Ann Scherzinger, Grace A McComsey, Jordan E Lake, James H Stein, Judith S Currier, Todd T Brown
OBJECTIVE: A greater burden of physical function impairment occurs in HIV-infected adults; the impact of antiretroviral therapy (ART) initiation on muscle density (less dense = more fat), a measure of muscle quality, is unknown. DESIGN: AIDS Clinical Trials Group Study A5260 s, a cardiometabolic substudy of A5257, randomized HIV-infected, ART-naïve adults to ritonavir-boosted atazanavir, darunavir, or raltegravir with tenofovir/emtricitabine backbone. Single-slice abdominal computed tomography (CT) scans from baseline and week 96 were reanalyzed for lean muscle area and density...
June 5, 2017: AIDS
https://www.readbyqxmd.com/read/28583191/hiv-drug-resistance-against-strand-transfer-integrase-inhibitors
#4
REVIEW
Kaitlin Anstett, Bluma Brenner, Thibault Mesplede, Mark A Wainberg
Integrase strand transfer inhibitors (INSTIs) are the newest class of antiretroviral drugs to be approved for treatment and act by inhibiting the essential HIV protein integrase from inserting the viral DNA genome into the host cell's chromatin. Three drugs of this class are currently approved for use in HIV-positive individuals: raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG), while cabotegravir (CAB) and bictegravir (BIC) are currently in clinical trials. RAL and EVG have been successful in clinical settings but have relatively low genetic barriers to resistance...
June 5, 2017: Retrovirology
https://www.readbyqxmd.com/read/28579016/executive-summary-of-the-gesida-national-aids-plan-consensus-document-on-antiretroviral-therapy-in-adults-infected-by-the-human-immunodeficiency-virus-updated-january-2017
#5
(no author information available yet)
Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives...
May 31, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28569776/hiv-integrase-inhibitor-elvitegravir-impairs-rag-functions-and-inhibits-v-d-j-recombination
#6
Mayilaadumveettil Nishana, Namrata M Nilavar, Rupa Kumari, Monica Pandey, Sathees C Raghavan
Integrase inhibitors are a class of antiretroviral drugs used for the treatment of AIDS that target HIV integrase, an enzyme responsible for integration of viral cDNA into host genome. RAG1, a critical enzyme involved in V(D)J recombination exhibits structural similarity to HIV integrase. We find that two integrase inhibitors, Raltegravir and Elvitegravir, interfered with the physiological functions of RAGs such as binding, cleavage and hairpin formation at the recombination signal sequence (RSS), though the effect of Raltegravir was limited...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28562771/facial-botryomycosis-like-pyoderma-in-an-hiv-infected-patient-remission-after-initiation-of-darunavir-and-raltegravir
#7
Walter de Araujo Eyer-Silva, Guilherme Almeida Rosa da Silva, Fernando Raphael de Almeida Ferry, Jorge Francisco da Cunha Pinto
Botryomycosis is an uncommon, chronic, suppurative, bacterial infection that primarily affects the skin and subcutaneous tissues. It has long been associated with defects of cellular immunity. We report a 28-year-old woman who presented with a chronic, ulcerated lesion with draining sinuses in the right malar region. Predisposing factors were HIV infection with poor immunological control, alcoholism, and a previous trauma to the right cheek. Several courses of antimicrobial therapy provided only partial and temporary remission...
March 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28533248/impact-of-hiv-1-integrase-l74f-v75i-mutations-from-a-clinical-isolate-on-resistance-to-second-generation-integrase-strand-transfer-inhibitors
#8
Atsuko Hachiya, Karen A Kirby, Yoko Ido, Urara Shigemi, Masakazu Matsuda, Reiko Okazaki, Junji Imamura, Stefan G Sarafianos, Yoshiyuki Yokomaku, Yasumasa Iwatani
A novel HIV-1 integrase mutation pattern, L74F/V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F/V75I to N155H or G140S/Q148H increased resistance levels to second-generation INSTIs, dolutegravir (>385-, 100-fold, respectively) and cabotegravir (153-, 197-fold, respectively). These findings are important for developing an accurate interpretation system of INSTI resistance and the rational design of next-generation INSTIs...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28520611/treatment-outcomes-of-third-line-antiretroviral-regimens-in-hiv-infected-thai-adolescents
#9
Wasana Prasitsuebsai, Jiratchaya Sophonphan, Kulkanya Chokephaibulkit, Jurai Wongsawat, Suparat Kanjanavanit, Pope Kosalaraksa, Chaiwat Ngampiyakul, Pakarat Sangkla, Rawiwan Hansudewechakul, Stephen J Kerr, Thanyawee Puthanakit, Jintanat Ananworanich
BACKGROUND: Efficacy and safety data of third-line antiretroviral (ARV) regimens in adolescents are limited. METHODOLOGY: This study enrolled HIV-infected Thais who were treated with third-line regimens consisting of darunavir/ritonavir (DRV/r), etravirine (ETR), tipranavir/ritonavir (TPV/r) or raltegravir (RAL). RESULTS: Fifty-four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48 weeks. Reasons for switch were second-line failure (n=44) and toxicity to second-line regimens (n=10)...
May 16, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28520610/candidates-for-inclusion-in-a-universal-antiretroviral-regimen-dolutegravir
#10
Pedro Cahn
PURPOSE OF REVIEW: The review addresses the role of dolutegravir (DTG) in first-line therapy. In the era of test and treat, where United Nations AIDS Program and WHO have set the ambitious targets of 90/90/90, new efficacious, well tolerated, and simple therapeutic options are needed. RECENT FINDINGS: DTG has been tested in large clinical trials in treatment-naïve patients, showing noninferiority to raltegravir and superiority compared with efavirenz and ritonavir-boosted darunavir, respectively...
July 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28508573/regional-differences-in-the-management-and-outcome-of-kidney-transplantation-in-patients-with-human-immunodeficiency-virus-infection-a-3-year-retrospective-cohort-study
#11
Marina P Cristelli, Federico Cofán, Helio Tedesco-Silva, Joan Carles Trullàs, Daniel Wagner C L Santos, Cristian Manzardo, Fernando Agüero, Asunción Moreno, Federico Oppenheimer, Fritz Diekmann, Jose O Medina-Pestana, Jose Maria Miro
BACKGROUND: In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES: We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS: This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT...
May 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28498892/incident-aids-or-death-after-initiation-of-human-immunodeficiency-virus-treatment-regimens-including-raltegravir-or-efavirenz-among-adults-in-the-united-states
#12
Stephen R Cole, Jessie K Edwards, H Irene Hall, M Alan Brookhart, W Christopher Mathews, Richard D Moore, Heidi M Crane, Mari M Kitahata, Michael J Mugavero, Michael S Saag, Joseph J Eron
Background.: The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown. Methods.: We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate)...
June 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28495562/nucleoside-reverse-transcriptase-inhibitor-cross-resistance-and-outcomes-from-second-line-antiretroviral-therapy-in-the-public-health-approach-an-observational-analysis-within-the-randomised-open-label-earnest-trial
#13
Nicholas I Paton, Cissy Kityo, Jennifer Thompson, Immaculate Nankya, Leonard Bagenda, Anne Hoppe, James Hakim, Andrew Kambugu, Joep J van Oosterhout, Mary Kiconco, Silvia Bertagnolio, Philippa J Easterbrook, Peter Mugyenyi, A Sarah Walker
BACKGROUND: Cross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV. METHODS: We did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa...
May 8, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28494325/hiv-1-integrase-inhibitor-resistance-among-treatment-na%C3%A3-ve-patients-in-the-west-of-scotland
#14
A Bradley-Stewart, C Urcia, A MacLean, C Aitken, R Gunson
BACKGROUND: Transmitted integrase inhibitor resistance is rare, with only a small number of cases reported world-wide to date. OBJECTIVES: The aim of this study was to assess whether transmitted integrase inhibitor resistance has occurred in Scotland and if so, could there be a case for performing genotypic integrase resistance testing at baseline. STUDY DESIGN: The study population consisted of 106 treatment naïve, newly diagnosed, HIV positive patients...
April 23, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28489061/microbial-natural-product-alternariol-5-o-methyl-ether-inhibits-hiv-1-integration-by-blocking-nuclear-import-of-the-pre-integration-complex
#15
Jiwei Ding, Jianyuan Zhao, Zhijun Yang, Ling Ma, Zeyun Mi, Yanbing Wu, Jiamei Guo, Jinmin Zhou, Xiaoyu Li, Ying Guo, Zonggen Peng, Tao Wei, Haisheng Yu, Liguo Zhang, Mei Ge, Shan Cen
While Highly Active Antiretroviral Therapy (HAART) has significantly decreased the mortality of human immunodeficiency virus (HIV)-infected patients, emerging drug resistance to approved HIV-1 integrase inhibitors highlights the need to develop new antivirals with novel mechanisms of action. In this study, we screened a library of microbial natural compounds from endophytic fungus Colletotrichum sp. and identified alternariol 5-O-methyl ether (AME) as a compound that inhibits HIV-1 pre-integration steps. Time-of addition analysis, quantitative real-time PCR, confocal microscopy, and WT viral replication assay were used to elucidate the mechanism...
May 10, 2017: Viruses
https://www.readbyqxmd.com/read/28480227/influence-of-sex-gender-and-race-on-responses-to-raltegravir-combined-with-tenofovir-emtricitabine-in-treatment-naive-human-immunodeficiency-virus-1-infected-patients-pooled-analyses-of-the-startmrk-and-qdmrk-studies
#16
Kathleen Squires, Linda-Gail Bekker, Christine Katlama, Yazdan Yazdanpanah, Yan Zhou, Anthony J Rodgers, Mark J DiNubile, Peter A Sklar, Randi Y Leavitt, Hedy Teppler
BACKGROUND: Antiretroviral therapy in human immunodeficiency virus (HIV)-infected women and blacks merits particular scrutiny because these groups have been underrepresented in clinical trials. METHODS: To document the effects of raltegravir across sex and racial lines, we conducted a pooled subgroup analysis of the efficacy and safety of raltegravir 400 mg BID plus tenofovir-emtricitabine by sex (women vs men) and self-identified race (black vs non-black) using phase 3 studies in treatment-naive patients...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28477212/efficacy-and-tolerability-of-switching-to-a-dual-therapy-with-darunavir-ritonavir-plus-raltegravir-in-hiv-infected-patients-with-hiv-1-rna-%C3%A2-50%C3%A2-cp-ml
#17
Giordano Madeddu, Stefano Rusconi, Alessandro Cozzi-Lepri, Simona Di Giambenedetto, Stefano Bonora, Alessia Carbone, Andrea De Luca, Nicola Gianotti, Antonio Di Biagio, Andrea Antinori
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. OBJECTIVES: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting...
May 5, 2017: Infection
https://www.readbyqxmd.com/read/28463882/impact-of-intensified-antiretroviral-therapy-during-early-hiv-infection-on-gut-immunology-and-inflammatory-blood-biomarkers-a-randomized-controlled-trial
#18
Connie J Kim, Rodney Rousseau, Sanja Huibner, Colin Kovacs, Erika Benko, Kamnoosh Shahabi, Gabor Kandel, Mario Ostrowski, Rupert Kaul
OBJECTIVE: Standard antiretroviral therapy (ART) is slow to reverse gut mucosal immune defects that cause persistent inflammation and immune activation. We examined whether intensifying early-administered ART through the addition of maraviroc and raltegravir would accelerate their resolution. DESIGN: ART-naïve men with early HIV infection were randomized in a double-blind manner to receive ART (emtricitabine/tenofovir disoproxil fumarate + lopinavir/ritonavir), together with either combined raltegravir/maraviroc or placebo, for 48 weeks...
May 1, 2017: AIDS
https://www.readbyqxmd.com/read/28453028/-antiretroviral-therapy-containing-raltegravir-in-hiv-infected-pregnant-women-systematic-review
#19
REVIEW
Lisset García-Fernández, Fabián Fiestas, Rubén Vásquez, Carlos Benites
INTRODUCTION: The risk of mother to child transmission (MTCT) of HIV increases in pregnant women diagnosed late in pregnancy. Some experts suggest that the use of raltegravir (RAL), as part of the antiretroviral treatment in these pregnant women, could reduce the risk of MTCT, since RAL can quickly decrease the viral load. OBJECTIVE: To evaluate the available scientific information on the efficacy and safety of RAL, during the third trimester of pregnancy, in reducing MTCT of HIV...
October 2016: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/28447585/metabolic-profiles-of-individuals-switched-to-second-line-antiretroviral-therapy-after-failing-standard-first-line-therapy-for-treatment-of-hiv-1-infection-in-a-randomized-controlled-trial
#20
Amanda H Yao, Cecilia L Moore, Poh Lian Lim, Jean-Michel Molina, Juan Sierra Madero, Stephen Kerr, Paddy Wg Mallon, Sean Emery, David A Cooper, Mark A Boyd
BACKGROUND: To investigate metabolic changes associated with second-line antiretroviral therapy (ART) following virological failure of first-line ART. METHODS: SECOND-LINE was an open-label randomized controlled trial. Participants were randomized 1:1 to receive ritonavir-boosted lopinavir (LPV/r) with 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI-group) or raltegravir (RAL-group) Two hundred and ten participants had a dual energy X-ray absorptiometry (DXA)-scan at baseline, week 48 and 96...
April 27, 2017: Antiviral Therapy
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