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https://www.readbyqxmd.com/read/28511058/stability-behavior-of-antiretroviral-drugs-and-their-combinations-7-comparative-degradation-pathways-of-lamivudine-and-emtricitabine-and-explanation-to-their-differential-degradation-behavior-by-density-functional-theory
#1
Moolchand Kurmi, Saranjit Singh
The interest in this study was to establish comparative degradation behavior of lamivudine (3TC) and emtricitabine (FTC) under solution and solid state stress conditions. Structurally, the two drugs differ only in terms of additional fluorine at 5 position in FTC. Along with the known degradation products of both the drugs, one additional degradation product was observed in each case, which was characterized by mass spectrometry. Both the drugs degraded via the same route, but at a differential rate in acid, base and oxidative stress conditions...
May 2, 2017: Journal of Pharmaceutical and Biomedical Analysis
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
#2
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/28489856/randomized-trial-of-stopping-or-continuing-art-among-postpartum-women-with-pre-art-cd4-%C3%A2-400-cells-mm3
#3
Judith S Currier, Paula Britto, Risa M Hoffman, Sean Brummel, Gaerolwe Masheto, Esau Joao, Breno Santos, Linda Aurpibul, Marcelo Losso, Marie F Pierre, Adriana Weinberg, Devasena Gnanashanmugam, Nahida Chakhtoura, Karin Klingman, Renee Browning, Anne Coletti, Lynne Mofenson, David Shapiro, Jose Pilotto
BACKGROUND: Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. METHODS: Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen...
2017: PloS One
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
#4
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/28470014/risk-of-acute-liver-injury-with-antiretroviral-therapy-by-viral-hepatitis-status
#5
Charitha Gowda, Craig W Newcomb, Qing Liu, Dena M Carbonari, James D Lewis, Kimberly A Forde, David S Goldberg, K Rajender Reddy, Jason A Roy, Amy R Marks, Jennifer L Schneider, Jay R Kostman, Janet P Tate, Joseph K Lim, Amy C Justice, Matthew Bidwell Goetz, Douglas A Corley, Vincent Lo Re
BACKGROUND: The risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status. METHODS: We followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Within the first year of ART, we determined occurrence of (1) liver aminotransferases >200 U/L and (2) severe ALI (coagulopathy with hyperbilirubinemia)...
2017: Open Forum Infectious Diseases
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
#6
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/28463880/medication-adherence-condom-use-and-sexually-transmitted-infections-in-australian-prep-users-interim-results-from-the-victorian-prep-demonstration-project
#7
Luxi Lal, Jennifer Audsley, Dean Murphy, Christopher K Fairley, Mark Stoove, Norm Roth, Richard Moore, B K Tee, Nalagafiar Puratmaja, Peter L Anderson, David Leslie, Robert M Grant, John De Wit, Edwina Wright
OBJECTIVE: HIV Pre-exposure prophylaxis (PrEP) decreases risk of HIV acquisition however its efficacy is closely dependent on adherence. There is also concern that the preventive effect of PrEP may be offset by risk compensation, notably an increase in condomless anal sex. DESIGN: Multi-site, open-label demonstration study that recruited people at current or recent risk of HIV infection in Melbourne, Australia. METHODS: Participants were recruited from three general practice clinics and one sexual health clinic in Melbourne and consented to take daily tenofovir/emtricitabine for 30 months...
May 1, 2017: AIDS
https://www.readbyqxmd.com/read/28453836/commonly-transmitted-hiv-1-drug-resistance-mutations-in-reverse-transcriptase-and-protease-in-antiretroviral-treatment-naive-patients-and-response-to-regimens-containing-tenofovir-disoproxil-fumarate-or-tenofovir-alafenamide
#8
Nicolas A Margot, Pamela Wong, Rima Kulkarni, Kirsten White, Danielle Porter, Michael E Abram, Christian Callebaut, Michael D Miller
Background.: The presence of transmitted drug resistance mutations (TDRMs) in antiretroviral treatment (ART)-naive patients can adversely affect the outcome of ART. Methods.: Resistance testing was conducted in 6704 ART-naive subjects predominantly from the United States and Europe in 9 clinical studies conducted by Gilead Sciences from 2000 to 2013. Results.: The presence of TDRMs increased during this period (from 5.2% to 11.4%), primarily driven by an increase in nonnucleoside reverse-transcriptase (RT) inhibitor (NNRTI) resistance mutations (from 0...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28449051/viral-kinetics-in-semen-with-different-antiretroviral-families-in-treatment-na%C3%A3-ve-hiv-infected-patients-a-randomized-trial
#9
Alicia Gutierrez-Valencia, Omar J Benmarzouk-Hidalgo, Inmaculada Rivas-Jeremías, Nuria Espinosa, María Trujillo-Rodríguez, Tamara Fernandez-Magdaleno, Pompeyo Viciana, Luis F López-Cortés
Background: There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of HIV-RNA decay in semen. Objective: To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma of treatment-naïve HIV-infected patients. Methods: Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-DF plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv)...
April 25, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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
#10
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
https://www.readbyqxmd.com/read/28444867/urine-assay-for-tenofovir-to-monitor-adherence-in-real-time-to-tenofovir-disoproxil-fumarate-emtricitabine-as-pre-exposure-prophylaxis
#11
H C Koenig, K Mounzer, G W Daughtridge, C E Sloan, L Lalley-Chareczko, G S Moorthy, S C Conyngham, A F Zuppa, L J Montaner, P Tebas
OBJECTIVES: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for pre-exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for the success of PrEP, but current adherence measurements are inadequate for real-time adherence monitoring. We developed and validated a urine assay to measure tenofovir (TFV) to objectively monitor adherence to PrEP. METHODS: We developed a urine assay using high-performance liquid chromatography coupled to tandem mass spectrometry with high sensitivity/specificity for TFV that allowed us to determine TFV concentrations in log10 categories between 0 and 10 000 ng/mL...
April 26, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28438932/evaluation-of-a-multi-drug-assay-for-monitoring-adherence-to-a-regimen-for-hiv-pre-exposure-prophylaxis-in-a-clinical-study-hiv-prevention-trials-network-073
#12
Yinfeng Zhang, William Clarke, Mark A Marzinke, Estelle Piwowar-Manning, Geetha Beauchamp, Autumn Breaud, Craig W Hendrix, Gavin A Cloherty, Lynda Emel, Scott Rose, Lisa Hightow-Weidman, Marc Siegel, Steven Shoptaw, Sheldon D Fields, Darrell Wheeler, Susan H Eshleman
Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is a safe and effective intervention for HIV pre-exposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs for assessing recent PrEP exposure (multi-drug assay; detection limit: 2-20 ng/mL). Samples were obtained from 216 Black men who have sex with men in the United States who were enrolled in a study evaluating acceptability of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) PrEP (208 HIV-uninfected men and eight seroconverters; 165 of the uninfected men and five of the seroconverters accepted PrEP)...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28418990/bone-density-microarchitecture-and-tissue-quality-following-long-term-treatment-with-tenofovir-emtricitabine-or-abacavir-lamivudine
#13
Robert Güerri-Fernández, Daniel Molina-Morant, Judit Villar-García, Sabina Herrera, Alicia González-Mena, Ana Guelar, Marta Trenchs-Rodríguez, Adolfo Díez-Pérez, Hernando Knobel
OBJECTIVES: HIV infection has been associated with reduced bone mineral density (BMD). Antiretroviral therapy has a deleterious effect on BMD, but its effect on bone fragility is not clear. The objective of this study is to analyze the BMD, microarchitecture and tissue quality of bone in patients receiving long-term tenofovir- or abacavir-based antiretroviral therapy. DESIGN: We conducted a cross-sectional study in HIV patients undergoing tenofovir or abacavir antiretroviral therapy for more than five years...
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28418232/high-pre-exposure-prophylaxis-uptake-and-early-adherence-among-men-who-have-sex-with-men-and-transgender-women-at-risk-for-hiv-infection-the-prep-brasil-demonstration-project
#14
MULTICENTER STUDY
Brenda Hoagland, Ronaldo I Moreira, Raquel B De Boni, Esper G Kallas, José Valdez Madruga, Ricardo Vasconcelos, Silvia Goulart, Thiago S Torres, Luana M S Marins, Peter L Anderson, Paula M Luz, Iuri da Costa Leite, Albert Y Liu, Valdilea G Veloso, Beatriz Grinsztejn
INTRODUCTION: The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW). METHODS: PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System...
April 6, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28403692/severe-hypokalemia-due-to-a-possible-drug-drug-interaction-between-vinblastine-and-antiretrovirals-in-a-hiv-infected-patient-with-hodgkin-s-lymphoma
#15
Ezequiel Cordova, Laura Morganti, Andrea Odzak, Florencia Arcondo, Mariana Silva, Marcelo Zylberman, Claudia Rodriguez
A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug--drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28403619/insulin-like-growth-factor-is-associated-with-changes-in-body-composition-with-antiretroviral-therapy-initiation
#16
Kristine M Erlandson, Suzanne P Fiorillo, Sandra Wagner Cardoso, Cynthia Riviere, Jorge Sanchez, James Hakim, Nagalingeswaran Kumarasamy, Sharlaa Badal-Faesen, Umesh Lalloo, Johnstone Kumwenda, Thomas B Campbell, Todd T Brown
Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have been associated with body composition changes among HIV-infected persons with wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with antiretroviral therapy (ART) initiation or differing ART therapies. The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized clinical trial of ART initiation with emtricitabine/tenofovir + efavirenz (FTC/TDF+EFV) versus lamivudine/zidovudine + efavirenz (3TC/ZDV+EFV) in HIV-1-infected individuals from resource-diverse settings...
May 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28403026/candidates-for-inclusion-in-a-universal-antiretroviral-regimen-are-lamivudine-and-emtricitabine-interchangeable
#17
Nathan Ford, Marco Vitoria, Meg Doherty, Andy Gray
PURPOSE OF REVIEW: Lamivudine (3TC) and emtricitabine (FTC) are the most widely used antiretroviral medications worldwide and are considered by the WHO to be interchangeable. This article reviews evidence supporting interchangeability of 3TC and FTC and considerations for future use. RECENT FINDINGS: Three randomized trials have directly compared the safety and efficacy of 3TC and FTC against identical backbone regimens. Each of these trials reported a nonsignificant difference in virological suppression, and when results were pooled the overall difference was nonsignificant (relative risk 1...
April 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28402499/structural-basis-for-the-d-stereoselectivity-of-human-dna-polymerase-%C3%AE
#18
Rajan Vyas, Andrew J Reed, Austin T Raper, Walter J Zahurancik, Petra C Wallenmeyer, Zucai Suo
Nucleoside reverse transcriptase inhibitors (NRTIs) with L-stereochemistry have long been an effective treatment for viral infections because of the strong D-stereoselectivity exhibited by human DNA polymerases relative to viral reverse transcriptases. The D-stereoselectivity of DNA polymerases has only recently been explored structurally and all three DNA polymerases studied to date have demonstrated unique stereochemical selection mechanisms. Here, we have solved structures of human DNA polymerase β (hPolβ), in complex with single-nucleotide gapped DNA and L-nucleotides and performed pre-steady-state kinetic analysis to determine the D-stereoselectivity mechanism of hPolβ...
April 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28383649/us-black-women-and-hiv-prevention-time-for-new-approaches-to-clinical-trials
#19
Adimora Adaora A, Stephen R Cole, Joseph J Eron
Black women bear the highest burden of HIV infection among US women. Tenofovir/emtricitabine HIV prevention trials among women in Africa have yielded varying results. Ideally, a randomized controlled trial (RCT) among US women would provide data for guidelines for US women's HIV pre-exposure prophylaxis use. However, even among US Black women at high risk for HIV infection, sample size requirements for an RCT with HIV incidence as its outcome are prohibitively high. We propose to circumvent this large sample size requirement by evaluating relationships between HIV incidence and drug concentrations measured among participants in traditional phase 3 trials in high incidence settings - and then applying these observations to drug concentrations measured among at risk individuals in lower incidence settings, such as US Black women...
April 5, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28383402/comparative-effectiveness-of-single-versus-multiple-tablet-antiretroviral-therapy-regimens-in-clinical-hiv-practice
#20
COMPARATIVE STUDY
Daniel R Drozd, Michael S Saag, Andrew O Westfall, William Chris Mathews, Richard Haubrich, Stephen L Boswell, Stephen R Cole, Donna Porter, Mari M Kitahata, Timothy Juday, Lisa Rosenblatt
We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. Temporal trends in care may have confounded results.
April 2017: Medicine (Baltimore)
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