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Milton Luiz Gorzoni, Sueli Luciano Pires, Lilian de Fátima Costa Faria, Márcia Regina Valadares Aguado, Miriam Carmen Santana
CONTEXT AND OBJECTIVE: A search in the SciELO and PubMed databases showed few studies on human immunodeficiency virus (HIV) positive individuals in long-term care institutions (LTCIs), thus prompting the present study. The aim of this study was to ascertain whether there were any HIV-positive individuals in LTCIs for the elderly. DESIGN AND SETTING: Cross-sectional study in which the Hospital Infection Control Committee (HICC) of a 405-bed LTCI was consulted. METHODS: The medical records of 405 individuals interned in the LTCI who had been tested for HIV infection were requested for analysis of the following variables: [1] age and gender; [2] length of stay at LTCI (months); [3] causes and diagnoses on admission to LTCI according to International Classification of Diseases, 10th edition; [4] date of HIV diagnosis; [5] seropositivity for syphilis and hepatitis B and C viruses; [6] medications used at last prescription in medical file; and [7] mean CD4 lymphocyte count based on: total lymphocyte count/6 and total lymphocyte count x 0...
October 13, 2016: São Paulo Medical Journal, Revista Paulista de Medicina
Linda Aurpibul, Sirinya Teerananchai, Wasana Prasitsuebsai, Tavitiya Sudjaritruk, Pope Kosalaraksa, Nia Kurniati, Khanh Huu Truong, Viet Chau Do, Lam Van Nguyen, Kulkanya Chokephaibulkit, Thida Singtoroj, Stephen J Kerr
BACKGROUND: Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring (TDM) can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate-to-high level LPV resistance in Asian children. MATERIALS AND METHODS: LPV concentration, HIV RNA level, and adherence data from study participants in Indonesia, Thailand, and Vietnam receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed...
August 1, 2016: Therapeutic Drug Monitoring
Martina Hahn, Sibylle C Roll
A 50-year-old male patient with comorbid human immunodeficiency virus developed a relapse of bipolar disorder after a switch from oral aripiprazole 10 mg/day to intramuscular aripiprazole depot 200 mg every 28 days plus oral aripiprazole 5 mg/day. The patient was concomitantly taking lopinavir, saquinavir, ritonavir, silybum marianum extract, and omeprazole. Only 1 week after the switch, the patient developed mood swings, irritability, depressive mood, and lack of drive. The oral aripiprazole was increased again to stabilize the patient...
December 2016: Drug Saf Case Rep
Motoko Ikuma, Dai Watanabe, Hiroki Yagura, Misa Ashida, Masaaki Takahashi, Masaaki Shibata, Tadafumi Asaoka, Munehiro Yoshino, Tomoko Uehira, Wataru Sugiura, Takuma Shirasaka
An elderly woman with human immunodeficiency virus-1 infection developed short bowel syndrome as a result of extensive intestinal resection. Considering the possibility of poor absorption of antiretroviral drugs (ARVs), therapeutic drug monitoring (TDM) was performed. A single-dose test of 6 ARVs (darunavir, ritonavir, lopinavir, etravirine, maraviroc, and raltegravir) did not provide information on the appropriate ARV, and repeated TDM under continuous antiretroviral therapy resulted in viral suppression below 50 copies/mL, which was considered to be treatment success...
2016: Internal Medicine
Mitch M Matoga, Mina C Hosseinipour, Evgenia Aga, Heather J Ribaudo, Nagalingeswaran Kumarasamy, John Bartlett, Michael D Hughes
BACKGROUND: Cardiovascular disease (CVD) is an emerging concern for HIV-infected patients. Hyperlipidemia is a risk factor for CVD and a complication of protease-inhibitor-based antiretroviral therapy, but little is known about its incidence and risk factors in treated patients in resource-limited settings (RLS). METHODS: We conducted a secondary analysis of ACTG A5230 trial in which HIV-infected adults from India, Malawi, Tanzania, Thailand and South Africa, with virologic relapse on first line therapy were initiated on lopinavir/ritonavir (LPV/r) monotherapy...
October 14, 2016: Antiviral Therapy
Paul Randell, Akil Jackson, Ana Milinkovic, Marta Boffito, Graeme Moyle
BACKGROUND: We aimed to measure the effect of raltegravir (RAL) on insulin sensitivity and surrogates of CV risk in healthy HIV-seronegative volunteers compared to that of lopinavir/r (LPV/r), a positive control. METHODS: An open label, two phase crossover study in HIV-negative male subjects randomized 1:1 to receive either 2 weeks of LPV/r followed by a two week washout period and two weeks of RAL, or RAL initially followed by LPV/r. A hyperinsulinaemic euglycaemic clamp was performed prior to and following each 2-week dosing phase...
October 6, 2016: Antiviral Therapy
Saran Vardhanabhuti, David Katzenstein, John Bartlett, Nagalingeswaran Kumarasamy, Carole L Wallis
Background.  The mechanism of virologic failure (VF) of lopinavir/ritonavir (LPV/r) monotherapy is not well understood. We assessed sequence changes in human immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions. Methods.  Human immunodeficiency virus-1 pol sequences from 34 participants who failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF. Sequence changes were evaluated using phylogenetic analysis and hamming distance. Results.  Human immunodeficiency virus-1 sequence change was higher over drug resistance mutation (DRM) sites (median genetic distance, 2...
September 2016: Open Forum Infectious Diseases
Bruce Green, Herta Crauwels, Thomas N Kakuda, Simon Vanveggel, Anne Brochot
BACKGROUND: Etravirine is a non-nucleoside reverse transcriptase inhibitor indicated in combination with other antiretrovirals for treatment-experienced HIV patients ≥6 years of age. Etravirine is primarily metabolized by cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A. This analysis determined the impact of concomitant antiretrovirals and CYP2C9/CYP2C19 phenotype on the pharmacokinetics of etravirine. METHODS: We used 4728 plasma concentrations from 817 adult subjects collected from four clinical studies to develop the population pharmacokinetic model...
September 24, 2016: Clinical Pharmacokinetics
Kenichiro Yaita, Shigeru Inoue, Takashi Horinouchi, Masahiro Kinoshita, Mitsuaki Unno, Osuke Iwata, Yuhei Tanaka, Kenji Gotoh, Mikio Ishibashi, Yoshiro Sakai, Kenji Masunaga, Hiroshi Watanabe, Masaki Tominaga
A 27-year-old HIV-infected pregnant Japanese woman was admitted to our hospital at gestational week 14. The patient's HIV viral load was 71,000 copies/mL, and her CD4 cell count was 147 cells/mm(3). Zidovudine, lamivudine, and lopinavir/ritonavir were administered at gestational week 18. Because the viral load increased to 222,000 copies/mL at the initiation of antiretroviral therapy, we added raltegravir. The decrease in the viral load was satisfactory, and a caesarean delivery was performed. Although the plasma concentration of raltegravir in the neonate was significantly high (2,482 ng/mL), no adverse event was confirmed...
2016: Internal Medicine
Masayuki Amano, Pedro Miguel Salcedo-Gómez, Rui Zhao, Ravikiran S Yedidi, Debananda Das, Haydar Bulut, Nicole S Delino, Sheri Venkata Reddy, Arun K Ghosh, Hiroaki Mitsuya
We here report that GRL-10413, a novel non-peptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (EC50: 0.00035 - 0.0018 μM) with minimal cytotoxicity (CC50: 35.7 μM). GRL-10413 blocked the infectivity and replication of HIV-1NL4-3 variants selected by up to 5 μM concentrations of atazanavir, lopinavir, or amprenavir (EC50: 0.0021 - 0.0023 μM). GRL-10413 also maintained its strong antiviral activity against multi-drug-resistant clinical HIV-1 variants isolated from patients, who no longer responded to various antiviral regimens after long-term antiretroviral therapy...
September 12, 2016: Antimicrobial Agents and Chemotherapy
Paola Maura Tricarico, Rafael Freitas de Oliveira Franca, Sabrina Pacor, Valentina Ceglia, Sergio Crovella, Fulvio Celsi
BACKGROUND: Prophylactic treatment regimens to prevent mother-to-child HIV transmission include protease inhibitors Lopinavir and Ritonavir. Lopinavir and Ritonavir have been reported to be able to induce intracellular oxidative stress in diverse cellular models, however scarce informations are available about protease inhibitor effects of in the central nervous system (CNS). In our study we evaluated the impact of protease inhibitors on a cell neuronal model. METHODS: We treated a neuroblastoma cell line (SH-SY5Y) with increasing doses of Lopinavir and Ritonavir (0...
2016: Cellular Physiology and Biochemistry
Thomas Tesson, Mathieu Blot, Aurélie Fillion, Hama Djerad, Joséphine Cagnon-Chapalain, Aline Creuwels, Anne Waldner, Michel Duong, Marielle Buisson, Sophie Mahy, Pascal Chavanet, Lionel Piroth
BACKGROUND: First-line antiretroviral therapy (1(st) ART) is an important step in a patient's management and often considered a long-term therapy at treatment initiation. METHODS: To describe the duration of 1(st) ART and the factors associated with treatment modification in a recent real-life setting, antiretroviral-naïve patients who began their 1(st)ART in six French hospitals in 2009-2012 were included in a cohort. Clinical, immunological, virological and therapeutic data, as well as the reasons for therapeutic changes, if any, were retrospectively collected...
September 7, 2016: Antiviral Therapy
Grishma M Patel, Pragna K Shelat, Anita N Lalwani
Aim of present work was to apply Quality by Design (QbD) principles for the development of proliposome of poorly soluble lopinavir (LPV). The patient-centric quality target product profile (QTPP) was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies were carried out to identify the probable risks affecting the CQAs of the product. On the basis of preliminary study, lipid: drug ratio and amount of carrier were selected as critical material attributes (CMAs) and were optimized by face centered central composite design...
August 29, 2016: European Journal of Pharmaceutical Sciences
Yin Mo, Dale Fisher
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been a focus of international attention since its identification in 2012. Epidemiologically it is characterized by sporadic community cases, which are amplified by hospital-based outbreaks. Healthcare facilities in 27 countries from most continents have experienced imported cases, with the most significant outbreak involving 186 cases in Korea. The mortality internationally is 36% and guidance for clinical management has yet to be developed. Most facilities and healthcare providers outside of the Middle East receiving patients have no or little experience in the clinical management of MERS...
September 1, 2016: Journal of Antimicrobial Chemotherapy
Retsilisitsoe R Moholisa, Michael Schomaker, Louise Kuhn, Sandra Castel, Lubbe Wiesner, Ashraf Coovadia, Renate Strehlau, Faeezah Patel, Francoise Pinillos, Elaine J Abrams, Gary Maartens, Helen McIlleron
BACKGROUND: Adequate exposure to antiretroviral drugs is necessary to achieve and sustain viral suppression. However, the target antiretroviral concentrations associated with long term viral suppression have not been adequately defined in children. AIM: We assessed the relationship between plasma lopinavir or nevirapine concentrations and the risk of subsequent viremia in children initially suppressed on antiretroviral therapy. METHODS: After an induction phase of antiretroviral treatment, 195 children with viral suppression (viral load ≤400 copies/mL) were randomized to continue a lopinavir/ritonavir-based regimen or to switch to a nevirapine-based regimen (together with lamivudine and stavudine)...
August 31, 2016: Pediatric Infectious Disease Journal
Jane Achan, Abel Kakuru, Gloria Ikilezi, Florence Mwangwa, Albert Plenty, Edwin Charlebois, Sera Young, Diane Havlir, Moses Kamya, Theodore Ruel
BACKGROUND: Diminished growth is highly prevalent among HIV-infected children and might be improved by antiretroviral therapy (ART). We examined growth recovery in a rural Ugandan cohort of HIV-infected children randomized to lopinavir/ritonavir or non-nucleoside-reverse-transcription-inhibitor-based ART. METHODS: HIV-infected children 2 months to 6 years of age were randomized to Lopinavir/ritonavir- or non-nucleoside-reverse-transcription-inhibitor-based ART. Changes in weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) Z-scores for 24 months were evaluated using generalized linear repeated-measures models...
August 30, 2016: Pediatric Infectious Disease Journal
Setha Limsreng, Olivier Marcy, Sowath Ly, Vara Ouk, Hak Chanroeurn, Saem Thavary, Ban Boroath, Ana Canestri, Gérald Viretto, Jean-François Delfraissy, Olivier Ségéral
BACKGROUND: Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity. METHODS: We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data...
2016: PloS One
Nicola Gianotti, Laura Galli, Renato Maserati, Laura Sighinolfi, Diego Ripamonti, Loredana Palvarini, Sergio Lo Caputo, Emanuele Focà, Benedetto Maurizio Celesia, Franco Baldelli, Gaetana Sterrantino, Adriano Lazzarin
In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receiving a standard triple antiretroviral therapy were randomized (1:1:1) to switch to monotherapy with darunavir/ritonavir (DRV/r-MT arm), monotherapy with lopinavir/ritonavir (LPV/r-MT arm) or to continue on the ongoing regimen (cART arm). The proportion (95% CI) of patients with virological success (Snapshot analysis) at week 48 was 73% (48%-90%) in the DRV/r-MT arm, 69% (42%-88%) in the LPV/r-MT arm and 87% (61%-98%) in the cART arm...
August 23, 2016: New Microbiologica
Abhirup Mandal, Dhananjay Pal, Ashim K Mitra
PURPOSE: This study was aimed to develop a novel Histidine-Leucine-Lopinavir (His-Leu-LPV) dipeptide prodrug and evaluate its potential for circumvention of P-gp and MRP2-mediated efflux of lopinavir (LPV) indicated for HIV-1 infection. METHODS: His-Leu-LPV was synthesized following esterification of hydroxyl group of LPV and was identified by (1)H NMR and LCMS/MS techniques. Aqueous solubility, stability and cell cytotoxicity of prodrug was determined. Uptake and permeability studies were carried out using P-gp (MDCK-MDR1) and MRP2 (MDCK-MRP2) transfected cell lines...
October 15, 2016: International Journal of Pharmaceutics
Robert T Maughan, Eoin R Feeney, Emilie Capel, Jacqueline Capeau, Pere Domingo, Marta Giralt, Joep M A Lange, Praphan Phanuphak, David A Cooper, Peter Reiss, Patrick W G Mallon
OBJECTIVES: Use of ART containing HIV PIs has previously been associated with toxicity in subcutaneous adipose tissue (SAT), potentially contributing to the development of lipodystrophy and insulin resistance. However, the effect of PIs on SAT function in ART-naive patients independent of other ART classes is unknown. This study aimed to elucidate the effect of initiating PI-only ART on SAT function in ART-naive subjects. METHODS: In the HIVNAT-019 study, 48 HIV-infected, ART-naive Thai adults commencing PI-only ART comprising lopinavir/ritonavir/saquinavir for 24 weeks underwent assessments of fasting metabolic parameters and body composition...
August 11, 2016: Journal of Antimicrobial Chemotherapy
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