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Sri Masyeni, Erly Sintya, Dewi Megawati, Ni Made Hegard Sukmawati, Dewa Ga Budiyasa, Sri Agung Aryastuti, Siti Qamariyah Khairunisa, Igkn Arijana, N Nasronudin
Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are the cornerstone of highly active antiretroviral therapy combination regimens for HIV infection. Unfortunately, NRTIs have been noticeably associated with many adverse effects related to mitochondrial toxicity leading to mitochondrial deoxyribonucleic acid (mtDNA) depletion. However, similar mitochondrial dysfunction has recently been found even in antiretroviral therapy-naïve patients, suggesting HIV itself could contribute to this abnormality...
2018: HIV/AIDS: Research and Palliative Care
Paige L Williams, Katharine Correia, Brad Karalius, Russell B Van Dyke, James D Wilkinson, William T Shearer, Steven D Colan, Steven E Lipshultz
OBJECTIVE: To evaluate potential adverse associations of individual antiretroviral medications (ARVs) used in combination antiretroviral therapy regimens on cardiac structure and function in youth with perinatally-acquired HIV infection (PHIV). DESIGN: PHIV youth (n = 325) enrolled in a prospective multisite cohort study had a single echocardiogram at age 7-16 years to evaluate cardiac function and structure. METHODS: We applied several statistical approaches to evaluate associations between use of 18 individual ARVs with Z-scores for 11 measures of left ventricular (LV) function and structure...
August 9, 2018: AIDS
Rakhi Gawali, Jay Trivedi, Sujit Bhansali, Raghunath Bhosale, Dhiman Sarkar, Debashis Mitra
1,3-oxazine nucleus and thiazolyl group features prominently in many biologically important natural products as well as bioactive molecules. A series of novel 2-thiazolyl substituted-2,3-dihydro-1H-naphtho [1,2-e][1,3]oxazine derivatives were designed and synthesized based on their structure-activity relationships (SARs) from 2-naphthol, substituted thiazolyl amines and formalin through ring closure by one-pot three component reaction. These derivatives were first evaluated for their inhibitory effect on HIV-1 Reverse Transcriptase (RT) enzyme activity...
July 31, 2018: European Journal of Medicinal Chemistry
Constance Delaugerre, Christophe Rodriguez, Catherine Capitant, Marie-Laure Nere, Mélanie Mercier-Darty, Diane Carette, Gilles Pialoux, Laurent Cotte, Isabelle Charreau, Jean-Michel Molina
BACKGROUND: The IPERGAY ANRS trial showed that on-demand pre-exposure prophylaxis (PrEP) with tenofovir (TDF) and emtricitabine (FTC) was highly effective in preventing HIV infection among highly exposed men who have sex with men. Here we analyzed drug resistance-associated mutations (RAMs) among all participants who acquired HIV infection during this trial. METHODS: Resistance was analyzed on frozen plasma at the time of HIV diagnosis among participants enrolled in the double-blind and open-label phases of the ANRS IPERGAY trial...
August 8, 2018: AIDS
Jayeeta Sarkar, Debraj Saha, Bhaswati Bandyopadhyay, Bibhuti Saha, Runu Chakravarty, Subhasish Kamal Guha
Background: Combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and efavirenz (EFV) is preferred in the treatment of HIV/hepatitis B virus (HBV) coinfection. We postulated that a HBV active nucleoside reverse transcriptase (RT) inhibitor/nucleotide RT inhibitor backbone of adefovir dipivoxil (ADV) +3TC would be as effective as TDF +3TC for the Indian population. Objective: ADV + 3TC could be an alternative option for these HIV/HBV coinfected individuals, preserving the dually active TDF + 3TC as second-line nucleoside backbone following failure of the first-line ART...
April 2018: Indian Journal of Medical Microbiology
Cecile Cames, Lea Pascal, Aissatou Ba, Hélène Mbodj, Baly Ouattara, Ndeye-Fatou Diallo, Philippe Msellati, Ngagne Mbaye, Haby Sy Signate, Stephane Blanche, Aminata Diack
BACKGROUND: The long-term benefits of antiretroviral treatment (ART) are associated with metabolic complications, especially lipodystrophy, which has been well described among HIV-infected adults and children on ART in developed settings. Specifically, stavudine, and to a lesser extent zidovudine and protease inhibitors (PI), have been consistently implicated in the development of lipodystrophy. In 2006, following advice from the WHO, Senegal began phasing out stavudine from first-line ART...
August 6, 2018: BMC Infectious Diseases
Miho Hachiman, Makoto Yoshimitsu, Chibueze Ezinne, Ayako Kuroki, Tomohiro Kozako, Naomichi Arima
Despite the efficacy of combination chemotherapy with arsenic trioxide (ATO), interferon α (IFN) and zidovudine (AZT) for adult T cell leukemia/lymphoma (ATL), the precise mechanism underlying this combination treatment effect is unknown. In the present study, ATO/IFN/AZT was examined in an ATL leukemic cell line (S1T, non-Tax expressing), a human T-lymphotropic virus 1 (HTLV-1)-infected cell line (MT2, Tax-expressing) and primary ATL cells from patients with acute and chronic ATL. IFN/AZT marginally inhibited MT2 cell proliferation, but substantially inhibited S1T cell proliferation...
July 2018: Oncology Letters
Ang Chen, Xiaojing Zhou, Yi Cheng, Shuowen Tang, Mingyao Liu, Xin Wang
Along with the prevalence of drug combination therapies, an increasing number of cases about drug-drug interactions (DDI) have been reported, which has drawn a lot of attention due to the potential toxicity and/or therapeutic failure. Pharmacokinetic interactions based on drug metabolic enzymes should be responsible for a great many of DDI. UDP-glucuronosyltransferases (UGT) as the main phase II metabolic enzymes are involved in the metabolism of many endogenous and exogenous substrates. Herein, we designed and optimized a validated cocktail method for the simultaneous evaluation of drug-mediated inhibition of the main five UGT isoforms using respective specific probe substrates (estradiol for UGT1A1, chenodeoxycholic acid for UGT1A3, serotonin for UGT1A6, propofol for UGT1A9/PROG and zidovudine for UGT2B7/AZTG) in human and rat liver microsomes by liquid chromatography-tandem mass spectrometry (LCMS/MS)...
October 1, 2018: Toxicology Letters
Giovanni Villa, Richard O Phillips, Colette Smith, Alexander J Stockdale, Alessandra Ruggiero, Apostolos Beloukas, Lambert T Appiah, David Chadwick, Fred S Sarfo, Anna Maria Geretti
Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care. Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI...
July 18, 2018: Journal of Antimicrobial Chemotherapy
Tewogbade Adeoye Adedeji, Simeon Adelani Adebisi, Nife Olamide Adedeji, Sikiru Abayomi Biliaminu, Timothy Olusegun Olanrewaju
BACKGROUND: Highly Active Antiretroviral Therapy (HAART) has been implicated in renal dysfunction with hypophosphataemia. OBJECTIVE: we prospectively evaluated renal phosphate excretion during HAART use. METHOD: Newly diagnosed human immunodeficiency virus (HIV)-infected individuals were treated with Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV), n=33; Zidovudine/Lamivudine /Nevirapine (ZDV/3TC/NVP), n=53; and Zidovudine/Lamivudine/Efavirenz (ZDV/3TC/EFV), n=16...
July 19, 2018: Infectious Disorders Drug Targets
Deborah Kacanek, Paige L Williams, Gloria Mayondi, Penny Holding, Jean Leidner, Kebaiphe Moabi, Vicki Tepper, Sharon Nichols, Joseph Makhema, Haruna Jibril, Tebogo Maididimalo, Roger Shapiro, Shahin Lockman, Betsy Kammerer
BACKGROUND: In utero exposure to nucleoside reverse transcriptase inhibitor (NRTI)-containing antiretroviral treatment (ART) regimens may be associated with poor neurodevelopmental functioning in children of HIV-infected mothers. We investigated neurodevelopmental outcomes of HIV-exposed uninfected (HEU) children of HIV-infected women enrolled in a randomized trial of abacavir/zidovudine/lamivudine (Triple-NRTI regimen) vs. lopinavir/ritonavir/zidovudine/lamivudine (Dual NRTI+PI regimen)...
July 10, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Salisu Abubakar, Garba Iliyasu, Farouq Muhammad Dayyab, Salisu Inuwa, Rabiu Alhassan Tudun Wada, Nasiru Magaji Sadiq, Muktar Ahmed Gadanya, Abdulrahman Abba Sheshe, Mohammad Sani Mijinyawa, Abdulrazaq Garba Habib
Background: Healthcare workers (HCWs) have an increased risk of occupational exposure to blood-borne pathogens. Aims/objectives: We aim to examine the utilisation and outcome of post-exposure prophylaxis (PEP) for both HIV and hepatitis B (HBV) among HCWs. Methods: This was a retrospective study conducted in a tertiary hospital in North-Western Nigeria. We reviewed data on HIV or HBV PEP given to HCWs between 2004 and 2016. Results: A total of 115 HCWs presented for PEP during the study period...
July 2018: Journal of Infection Prevention
Adane Teshome Kefale, Tegene Legese Dadi, Tessema Tsehay Biru, Teshale Ayele Mega
Background: Findings from different studies report inferior clinical and virologic efficacy with TDF/3TC/NVP. But, some studies show that, there was no statistically significant difference in mortality among ZDV and TDF based regimens. The objective of this review was to systematically identify, appraise and synthesize the best available evidence on efficacy and safety of TDF based regimen as compared to ZDV based regimens. Methods: A three-step search strategy was used to locate published and unpublished studies...
2018: Open AIDS Journal
Nguyễn Hoàng Ly, Thanh Danh Nguyen, Sang-Woo Joo
Zidovudine (AZT) adsorbed on colloidal gold nanoparticles (AuNPs) undergoes pH-induced conformational changes according to spectral changes in surface-enhanced Raman scattering (SERS). In acidic pH values conditions, AZT assumes the C(2') -endo conformer, which binds more weakly to AuNPs than under neutral and alkaline conditions. In this study, density functional theory (DFT) calculations were performed; these calculations also supported the conformation-dependent binding energies. A lactobionic acid-conjugated PEGylated (LA-PEG-SH; molecular weight: 3400) unit was attached to AuNPs to target the asialoglycoprotein receptors overexpressed in hepatocarcinoma cells of Huh7 and SNU-354...
May 19, 2018: Colloids and Surfaces. B, Biointerfaces
Geysa Maria Nogueira Farias, José Reginaldo Pinto, Juliana Carneiro Melo, Lara Gurgel Fernandes Távora, Danielle Malta Lima, Fernanda Judith Viana Correia, Geraldo Bezerra da Silva Júnior
Kyrle's disease (KD) is a rare skin pathology characterized by transepidermal elimination of abnormal keratin. The aim of this article is to report a rare case of KD associated with diabetes mellitus, chronic kidney disease, and HIV. A 51-year-old male patient complained of diarrhea for 8 months. He was submitted to HIV testing, which showed a positive result. He started antiretroviral therapy with zidovudine, lamivudine, and lopinavir. The diagnostic investigation was negative for opportunistic diseases. After 2 months, skin lesions started appearing, characterized by hyperchromic, pruritic macules and papules distributed in the trunk, back, and upper limbs...
July 2018: Indian Journal of Pathology & Microbiology
Somer L Smith, Ann M Chahroudi, Andres F Camacho-Gonzalez, Scott Gillespie, Bridget A Wynn, Martina L Badell, Andrea Swartzendruber, Rohan Hazra, Pascale Wortley, Rana Chakraborty
Objective: Our goal was to evaluate the infrastructure of programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) in major delivery units in the Atlanta, Georgia, metropolitan statistical area and to assess the knowledge, attitude, and practice of providers in these facilities around PMTCT. Methods: Hospital assessments and individual knowledge and practices were surveyed among 71 healthcare providers from March 2015 to March 2016 in 11 hospitals that deliver 40000 infants annually, which represents 70% of all deliveries in the Atlanta metropolitan statistical area...
July 6, 2018: Journal of the Pediatric Infectious Diseases Society
L Cunnama, E J Abrams, L Myer, A Gachuhi, N Dlamini, T Hlophe, J Kikuvi, N Langwenya, S Mthethwa, D Mudonhi, B Nhlabatsi, H Nuwagaba-Biribonwoha, V Okello, R Sahabo, A Zerbe, E Sinanovic
OBJECTIVES: To assess the costs and cost-effectiveness of transitioning from antiretroviral therapy (ART) initiation based on CD4 cell count and WHO clinical staging ('Option A') to universal ART ('Option B+') for all HIV-infected pregnant and breastfeeding women in Swaziland. METHODS: We measured the total costs of prevention of mother-to-child HIV transmission (PMTCT) service delivery at public sector facilities with empirical cost data collected at three points in time: once under Option A and again twice after transition to the Option B+ approach...
June 29, 2018: Tropical Medicine & International Health: TM & IH
S M T Cavalcanti, C Nunes, S A Costa Lima, J L Soares-Sobrinho, S Reis
An adapted methodology for obtaining lipid nanoparticles that only uses the microwave reactor in the synthesis process was developed. The method has the following features: one-pot, one-step, fast, practical, economical, safe, readiness of scaling-up, lack of organic solvents and production of nanoparticles with low polydispersity index (PDI) (below 0.3). This new method was applied for the development of nanostructured lipid carriers (NLC) loaded with a hydrophilic drug, the antiretroviral agent zidovudine (AZT)...
September 15, 2018: European Journal of Pharmaceutical Sciences
Chen Xu, Jie Gao, Hai-Feng Zhang, Na Gao, Yuan-Yuan Guo, Yan Fang, Qiang Wen, Hai-Ling Qiao
UDP-glucuronosyltransferase 2B7 (UGT2B7) is one of the most significant isoforms of UGTs in human liver. This research measured UGT2B7 protein content and activities including Vmax and CLint in human liver at isoform, microsomal, liver tissue, and liver levels and identified the factors that influence expression. We determined absolute protein content by LC-MS/MS and activities using the probe drug Zidovudine in 82 normal human liver microsomes. Using a bottom-up method for derivation, we showed UGT2B7 content at the microsomal, liver tissue, and liver levels, as well as activities at the isoform, microsomal, liver tissue, and liver levels in vitro, and predicted hepatic clearance in vivo, with median, range, variation, and 95 and 50% prediction intervals...
June 21, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Emily H Adhikari, Devin Macias, Donna Gaffney, Sarah White, Vanessa L Rogers, Donald D McIntire, Scott W Roberts
BACKGROUND: False positive HIV screening tests in pregnancy may lead to unnecessary interventions in labor. In 2014, the Centers for Disease Control and Prevention released a new algorithm for HIV diagnosis using a 4th generation screening test, which detects antibodies to HIV as well as p24 antigen and has a shorter window period compared with prior generations. A reactive screen requires a differentiation assay, and supplemental qualitative RNA testing is necessary for nonreactive differentiation assay...
June 15, 2018: American Journal of Obstetrics and Gynecology
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