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Rebecca Begley, Moupali Das, Lijie Zhong, John Ling, Brian P Kearney, Joseph M Custodio
BACKGROUND: Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete regimen (elvitegravir/cobicistat/emtricitabine (F)/tenofovir alafenamide (TAF), rilpivirine/F/TAF, bictegravir/F/TAF), or for use with other ARVs (F/TAF), for treatment of HIV. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Disposition of TAF may be altered by co-medications that can inhibit or induce P-gp or BCRP transporters...
April 10, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Timothy J Henrich
No abstract text is available yet for this article.
April 6, 2018: Lancet HIV
Thomas A Rasmussen, James H McMahon, J Judy Chang, Jennifer Audsley, Ajantha Rhodes, Surekha Tennakoon, Ashanti Dantanarayana, Tim Spelman, Tina Schmidt, Stephen J Kent, Vincent Morcilla, Sarah Palmer, Julian H Elliott, Sharon R Lewin
BACKGROUND: Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment. METHODS: In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia...
April 6, 2018: Lancet HIV
Jean Cyr Yombi
Integrase strand transfer inhibitors (INSTIs) are a newer class of antiretroviral treatment for HIV-infected patient. INSTIs currently available for use are raltegravir, elvitegravir, dolutegravir (DTG), and bictegravir. Clinical studies using INSTIs have demonstrated an 80-90% efficiency in treating HIV-positive antiretroviral therapy - naive patients. They are recommended by internatioal guidelines as the preferred agents for the first-line regimen. INSTIs have also been demonstrated as safe and tolerable...
January 2018: AIDS Reviews
Milena M McLaughlin, Aimee J Guerrero, Andrew Merker
A review of literature published regarding non-tenofovir antiretroviral agents causing renal adverse effects was conducted. The literature involving renal adverse effects and antiretroviral therapy is most robust with protease inhibitors, specifically atazanavir and indinavir, and includes reports of crystalluria, leukocyturia, nephritis, nephrolithiasis, nephropathy and urolithiasis. Several case reports describe potential nephropathy (including Fanconi syndrome) secondary to administration of abacavir, didanosine, lamivudine and stavudine...
2018: Drugs in Context
Charlotte Martin, Marie-Christine Payen, Stephane De Wit
Dolutegravir is an increasingly-used second-generation human immunodeficiency virus integrase strand transfer inhibitor. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome has been described in several patients treated with raltegravir but to our knowledge, there is no previous report of DRESS syndrome associated with dolutegravir.
January 1, 2018: International Journal of STD & AIDS
Hanh T Pham, Lydia Labrie, Ingeborg E A Wijting, Said Hassounah, Ka Yee Lok, Inna Portna, Mark Goring, Yingshan Han, Cynthia Lungu, Marchina E van der Ende, Bluma G Brenner, Charles A Boucher, Bart J A Rijnders, Jeroen J A van Kampen, Thibault Mesplède, Mark A Wainberg
Background: Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI) used for treatment of HIV-infected individuals. Due to its high genetic barrier to resistance, DTG has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virological failure while using DTG monotherapy...
March 29, 2018: Journal of Infectious Diseases
Ingeborg E A Wijting, Cynthia Lungu, Bart J A Rijnders, Marchina E van der Ende, Hanh T Pham, Thibault Mesplede, Suzan D Pas, Jolanda J C Voermans, Rob Schuurman, David A M C van de Vijver, Patrick H M Boers, Rob A Gruters, Charles A B Boucher, Jeroen J A van Kampen
Background: A high genetic resistance barrier to the integrase-strand-transfer-inhibitor (INSTI) dolutegravir has been reported in vitro and in vivo. We describe the dynamics of INSTI-resistance-associated-mutations (INSTI-RAMs) and mutations in the 3'-polypurine tract (3'-PPT) in relation to virological failure (VF) observed in the randomized dolutegravir maintenance monotherapy study (DOMONO, NCT02401828). Methods: From ten patients with VF plasma samples prior to start cART and during VF were used to generate Sanger sequences of integrase, the 5' terminal bases of the 3'- LTR, and the 3'-PPT...
March 29, 2018: Journal of Infectious Diseases
Daniel R Kuritzkes
No abstract text is available yet for this article.
March 29, 2018: Journal of Infectious Diseases
Jose L Blanco, Jhon Rojas, Roger Paredes, Eugenia Negredo, Josep Mallolas, Maria Casadella, Bonaventura Clotet, Jose M Gatell, Elisa de Lazzari, Esteban Martinez
Background: No controlled comparisons between dolutegravir/lamivudine or dolutegravir maintenance therapy have been done. We hypothesized that these options would have similar efficacy to triple ART. Methods: We used an open-label non-inferiority randomized controlled trial comprising two phases: phase A was established to test that experimental arms did not have an unacceptable (≥5%) failure rate; phase B was intended to include the full number of patients followed for 48 weeks...
March 28, 2018: Journal of Antimicrobial Chemotherapy
Amy Zheng, Nagalingeswaran Kumarasamy, Mingshu Huang, A David Paltiel, Kenneth H Mayer, Bharat B Rewari, Rochelle P Walensky, Kenneth A Freedberg
INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended for first-line HIV treatment in the US and Europe. Efavirenz (EFV)-based regimens remain the standard of care (SOC) in India. We examined the clinical and economic impact of DTG-based first-line ART in the setting of India's recent guidelines change to treating all patients with HIV infection regardless of CD4 count. METHODS: We used a microsimulation of HIV disease, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model, to project outcomes in ART-naive patients under two strategies: (1) SOC: EFV/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC); and (2) DTG: DTG + TDF/3TC...
March 2018: Journal of the International AIDS Society
A Borghetti, G Baldin, F Lombardi, A Ciccullo, A Capetti, S Rusconi, G Sterrantino, A Latini, M V Cossu, R Gagliardini, A De Luca, S Di Giambenedetto
OBJECTIVES: We evaluated the efficacy and tolerability of lamivudine + dolutegravir in a cohort of HIV-1 infected, treatment-experienced patients with undetectable HIV-RNA. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) and their predictors were assessed in a multicenter cohort of HIV-1 infected patients, starting lamivudine + dolutegravir after reaching viral suppression. Secondary objective was the evaluation of changes in lipid profile, renal and immunological functions at week 48...
March 24, 2018: HIV Medicine
Cynthia N Schreiner, Charles E Ahlfors, Ronald J Wong, David K Stevenson, Diana F Clarke, Mark Mirochnick
We performed an in vitro evaluation of the effect of maraviroc or dolutegravir on bilirubin to albumin binding. At typical treatment and low albumin concentrations, maraviroc had no impact, while dolutegravir affected bilirubin to albumin binding to an equivalent extent as sulfisoxazole. However in vivo, neither is likely to significantly impact bilirubin to albumin binding due to their low concentrations relative to albumin.
March 15, 2018: Pediatric Infectious Disease Journal
Eugenia Bruzzese, Andrea Lo Vecchio, Andrea Smarrazzo, Orsola Tambaro, Giulia Palmiero, Giovanni Bonadies, Alfredo Guarino
BACKGROUND: Treatment of HIV infection in adolescents is challenging due to long duration of therapy and poor adherence. Recently, the integrase strand transfer inhibitor dolutegravir (DTG) has been approved for the use in adolescents with HIV, but evidence in clinical practice is very limited. METHODS: We describe six cases of HIV-infected children/adolescents successfully treated with DTG-based regimen. Data relative to children/adolescents managed at the Referral Center for Pediatric HIV/AIDS of the University of Naples were reviewed...
March 20, 2018: Italian Journal of Pediatrics
Hsin-Yun Sun, Sui-Yuan Chang, Chien-Ching Hung
PURPOSE OF REVIEW: With prolonged life expectancy in HIV-positive patients on combination antiretroviral therapy, the quest for reducing lifelong drug exposure and minimizing or avoiding the toxicities of combination antiretroviral therapy while maintaining viral suppression has emerged when coformulations of antiretroviral agents with improved convenience, and better tolerability and efficacy became available. This review aims to update the current experience with the novel two-drug combination of dolutegravir (DTG) and rilpivirine (RPV) and elucidate the possible applications and limitations of coformulated DTG-RPV in the future...
March 16, 2018: Current Opinion in HIV and AIDS
Deniz Gokengin, Cristiana Oprea, Josip Begovac, Andrzej Horban, Arzu Nazlı Zeka, Dalibor Sedlacek, Bayjanov Allabergan, Esmira A Almamedova, Tatevik Balayan, Denes Banhegyi, Pavlina Bukovinova, Nikoloz Chkhartishvili, Alymbaeva Damira, Edona Deva, Ivaylo Elenkov, Luljeta Gashi, Dafina Gexha-Bunjaku, Vesna Hadciosmanovic, Arjan Harxhi, Tiberiu Holban, Djorje Jevtovic, David Jilich, Justyna Kowalska, Djhamal Kuvatova, Natalya Ladnaia, Adkhamjon Mamatkulov, Aleksandra Marjanovic, Maria Nikolova, Mario Poljak, Kristi Rüütel, Azzaden Shunnar, Milena Stevanovic, Zhanna Trumova, Oleg Yurin
OBJECTIVES: The aim of this survey was to describe the current status of HIV care in Central and Eastern European countries and to look at how close the region is to achieve the UNAIDS 2020 target of 90-90-90. METHODS: In 2014 data were collected from 24 Central and Eastern European countries by a 38-item questionnaire. RESULTS: All countries reported mandatory screening of blood and organ donors for HIV. Other groups who were subjected to targeted screening were people who inject drugs (PWID) (15/24; 62...
March 14, 2018: International Journal of Infectious Diseases: IJID
Dominik Brado, Adetayo Emmanuel Obasa, George Mondinde Ikomey, Ruben Cloete, Kamalendra Singh, Susan Engelbrecht, Ujjwal Neogi, Graeme Brendon Jacobs
HIV-Integrase (IN) has proven to be a viable target for highly specific HIV-1 therapy. We aimed to characterize the HIV-1 IN gene in a South African context and identify resistance-associated mutations (RAMs) against available first and second generation Integrase strand-transfer inhibitors (InSTIs). We performed genetic analyses on 91 treatment-naïve HIV-1 infected patients, as well as 314 treatment-naive South African HIV-1 IN-sequences, downloaded from Los Alamos HIV Sequence Database. Genotypic analyses revealed the absence of major RAMs in the cohort collected before the broad availability of combination antiretroviral therapy (cART) and INSTI in South Africa, however, occurred at a rate of 2...
March 16, 2018: Scientific Reports
Paul Mel van Dam, Mark Wl van Geffen, Thomas Ra Havenith, Dirk Posthouwer
Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine. Overdoses with Triumeq have not been reported previously. We present a case of a 26-year-old man who presented to our hospital after intentionally ingesting 30 tablets of Triumeq. An intoxication with Triumeq can lead to several side effects. An overdose of abacavir and lamivudine can cause mitochondrial toxicity and lactic acidosis. An intoxication with dolutegravir appears to be relatively harmless...
March 13, 2018: Antiviral Therapy
Rosario Palacios, M Mayorga, C M González-Domenech, C Hidalgo-Tenorio, C Gálvez, L Muñoz-Medina, J de la Torre, A Lozano, M Castaño, M Omar, Jesús Santos
OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42...
January 2018: Journal of the International Association of Providers of AIDS Care
Charlotte Charpentier, Gilles Peytavin, Minh P Lê, Véronique Joly, Ornella Cabras, Marine Perrier, Sylvie Le Gac, Bao Phung, Yazdan Yazdanpanah, Diane Descamps, Roland Landman
Objectives: To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to a dolutegravir-based regimen, regardless of the genotypic susceptibility score (GSS). Patients and methods: This was an observational single-centre study assessing ART-treated patients with plasma viral load (pVL) <50 copies/mL who were switched to a dolutegravir-based regimen with 1 year of follow-up. PCR negative was defined as an undetected PCR signal...
March 8, 2018: Journal of Antimicrobial Chemotherapy
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