19 results on '"Sahloff EG"'
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2. PIN42 DESIGNING AND TESTING A HIV-PATIENT SATISFACTION SURVEY FOR A COMPARITIVE ANALYSIS OF MAIL-ORDER PHARMACYVS. COMMUNITY PHARMACY SERVICES
- Author
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Ramasamy, A, primary, Pinto, SL, additional, and Sahloff, EG, additional
- Published
- 2008
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3. Exogenous cushing syndrome with inhaled fluticasone in a child receiving lopinavir/ritonavir.
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Bhumbra NA, Sahloff EG, Oehrtman SJ, and Horner JM
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- 2007
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4. A Narrative Review of Novel Agents for Managing Heavily Treatment-Experienced People Living With HIV.
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Beran C, Duggan JM, and Sahloff EG
- Abstract
Objective: The objective of this review is to compare ibalizumab, fostemsavir, and lenacapavir, present the clinical trials evaluating each agent, and provide guidance on their use in highly-treatment experienced (HTE) population living with HIV (PWH). Data sources: A search of PubMed and clinicaltrials.gov was conducted using the search terms: ibalizumab, fostemsavir, and lenacapavir. Study selection and data extraction: English-language, clinical publications were included. Data synthesis: Ibalizumab, fostemsavir, and lenacapavir, are each first-in-class agents, that have major differences in mechanism of action, route and frequency of administration, pharmacokinetic parameters, including elimination half-life, potential for drug-drug interactions, safety profiles, and cost. Each has been shown, when combined with an optimized background regimen (OBR) with at least one other active agent, to achieve virologic suppression in HTE-PWH. Conclusion: In HTE-patients, adding ibalizumab, fostemsavir, and/or lenacapavir to at least one other active agent can lead to virologic suppression in this difficult to treat population. Monotherapy with any of these agents is not recommended and will lead to a high likelihood of drug resistance. Selection of which agent(s) to include with an OBR will depend on other patient factors including concomitant medications, acceptance of formulations (oral vs. subcutaneous vs. intravenous infusion), and potential access (both insurance-based and transportation). Adherence to all agents in the regimen is paramount to successful outcomes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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5. The Role of Community Pharmacies in Providing Access to HIV Post-exposure Prophylaxis (PEP).
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Scarnati K, Esser K, Sahloff EG, and Duggan J
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- Humans, United States, Post-Exposure Prophylaxis, HIV Infections epidemiology, Pharmacies, Anti-HIV Agents therapeutic use, Acquired Immunodeficiency Syndrome
- Abstract
HIV affects an estimated 1.2 million individuals in the United States and is disproportionately concentrated among African Americans, Latinos, and people of multiple races. Post-exposure prophylaxis (PEP) substantially decreases HIV transmission when started within 72 h after exposure, but problems of accessibility have hindered its widespread usage in communities at risk for HIV infection. Pharmacy-initiated PEP access was first permitted in New York City in 2017, allowing pharmacists to provide a 7-day supply of PEP without a prescription for consumers at high risk for HIV infection. It was expected that the broad reach and accessibility of community pharmacies would increase timely access to PEP for all individuals, especially those who already face significant barriers to accessing the healthcare system. Since then, eleven other states have followed suit and expanded the scope of outpatient pharmacy practice in order to increase the availability of HIV PEP but prescribing laws in over 75% of the US have not been changed. Much of the existing literature on HIV prevention focuses on PrEP access barriers with limited information on PEP access in the US. In this paper, we review the current status of pharmacist-initiated PEP in the US as part of the End the HIV Epidemic (EHE) initiative., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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6. Personalizing prevention: Advances in pharmacotherapy for HIV prevention.
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Brizzi M, Sherman EM, Green SB, Nowicki DN, Drwiega EN, Nicol MR, Chastain DB, Sahloff EG, Truong WR, Cluck D, Badowski ME, Michienzi SM, and Durham SH
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- Female, Humans, United States, Emtricitabine therapeutic use, HIV Infections drug therapy, HIV Infections prevention & control, Anti-HIV Agents
- Abstract
The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence., (© 2023 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)
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- 2023
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7. Is Long-acting Cabotegravir a Pre-exposure Prophylaxis Option for Women of Childbearing Potential?
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Sahloff EG, Hamons N, Baumgartner K, and Duggan JM
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Long-acting cabotegravir (CAB-LA) provides an exciting new option for pre-exposure prophylaxis (PrEP) in multiple populations. In this Perspective, we consider the unique pharmacokinetics of CAB-LA and the potential impact on the prescribing of CAB-LA, specifically in cis-women of reproductive potential., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2022
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8. Use of an On-Site Outpatient Pharmacy for Acquisition of Antiretroviral Medications Compared to Off-Site Pharmacy Options: Impact on Retention in Care and Clinical Outcomes in People Living With HIV.
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Lauer BR, Duggan JM, Eitniear L, Jung R, and Sahloff EG
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- Humans, Outpatients, Retrospective Studies, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Pharmacies, Pharmacy, Retention in Care
- Abstract
Background: Few published studies have examined the relationship between pharmacy location and retention in care or clinical outcome in people living with HIV (PLWH)., Objective: The study purpose was to determine whether using an on-site/in-clinic pharmacy to obtain antiretroviral therapy increased retention in care and virologic suppression rates., Methods: PLWH attending a Ryan White outpatient clinic in an academic center were matched based on age and insurance. Rates of retention in care ( ≥2 medical visits/calendar year) were assessed between patients using a pharmacy on-site in the clinic versus patients use off-site pharmacy options. Virologic suppression [viral load(VL)<200 copies/mL], completing ≥2 VL, and CD4 count were compared between pharmacy types., Results: 137 on-site pharmacy patients and 274 off-site pharmacy patients met inclusion and matching criteria. 91.2% of on-site pharmacy users attended ≥2 clinic visits compared to 83.2% of off-site pharmacy users ( P = .0275) and were approximately twice as likely to complete ≥2 clinic visits (odds ratio: 2.032; 1.071-3.857). A similar proportion of the on-site pharmacy group achieved virologic suppression compared to the off-site pharmacy group (92.7% vs 89.1%; P = .239, respectively)., Conclusions: On-site pharmacies may provide an opportunity to positively impact retention in care and clinical outcomes for PLWH.
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- 2021
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9. Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation.
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Sahloff EG and Duggan JM
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- Adult, Aged, Anti-HIV Agents pharmacokinetics, Darunavir pharmacology, Drug Resistance, Viral, Emtricitabine pharmacology, Female, Humans, Male, Middle Aged, Mutation, Retrospective Studies, Ritonavir pharmacology, Treatment Outcome, Young Adult, Anti-HIV Agents therapeutic use, Darunavir therapeutic use, Emtricitabine therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Ritonavir therapeutic use
- Abstract
Background: Limited data exist on the use of a boosted protease inhibitor plus <2 active nucleoside/nucleotide reverse transcriptase inhibitors without use of additional classes of antiretroviral (ARV) therapy in treatment-experienced patients with background resistance., Objective: To evaluate clinical outcomes in HIV-infected patients harboring single- or multiclass resistant virus and receiving once-daily tenofovir/emtricitabine (TDF/FTC) plus darunavir/ritonavir (DRV/r) administered for >24 weeks., Methods: This was a single-center chart review of HIV-infected patients receiving daily TDF/FTC plus DRV/r and identified with resistant virus (including, but not limited to, an M184V/I). The primary outcome was HIV viral load (VL) <200 copies/mL (cp/mL) at last measurement. Additional end points included virological rebound (VR), resuppression, or failure (VF); VL <40 cp/mL at last measurement; and development of additional mutations., Results: Of 171 eligible patients, 32 were included in the study and received DRV 800 mg/r 100 mg daily with fixed-combination TDF/FTC. All patients had a baseline M184V/I mutation, with 10 (31%) having resistance to TDF; 27 (84%) achieved a VL <200 cp/mL, and 25(78%) had a VL <200 cp/mL at the last reading; 22 (69%) achieved a VL <40 cp/mL. VF occurred in 6/32 (19%) patients and VR in 1/32 (3%) patients. Conclusion and Relevance: Although providing a regimen containing ≤2 active drugs, the use of once-daily DRV/r plus TDF/FTC in treatment-experienced patients with single-/multiclass resistant virus resulted in virological suppression in more than three-fourths of patients. These retrospective data suggest that despite the presence of an M184V/I, this combination may be an option in patients seeking a once-daily ARV therapy to improve adherence.
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- 2019
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10. Evaluation of Serum Creatinine Changes With Integrase Inhibitor Use in Human Immunodeficiency Virus-1 Infected Adults.
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Lindeman TA, Duggan JM, and Sahloff EG
- Abstract
This retrospective chart review evaluated changes in serum creatinine and creatinine clearance (CrCl) after initiation of an integrase inhibitor (INSTI)-based regimen as initial treatment in human immunodeficiency virus-infected adults. Serum creatinine and CrCl changes were similar to those seen in clinical trials for INSTIs. No renal-related serious adverse events or discontinuations occurred.
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- 2016
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11. Alternative antiretroviral therapy formulations for patients unable to swallow solid oral dosage forms.
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Duggan JM, Akpanudo B, Shukla V, Gutterson G, Eitniear L, and Sahloff EG
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- Evidence-Based Medicine, HIV Infections drug therapy, Humans, Anti-Retroviral Agents therapeutic use, Deglutition Disorders, Dosage Forms
- Abstract
Purpose: Evidence-based guidance is presented to assist clinicians in selecting alternative formulations of antiretroviral (ARV) agents for patients with human immunodeficiency virus (HIV) infection who are unable to swallow tablets or capsules., Summary: The inability to take medications in standard oral dosage forms can be associated with nonadherence or the use of alternative administration strategies such as capsule or tablet breaking, crushing, or chewing. Patients with HIV infection require long-term ARV therapy to maintain viral suppression; ARV agents are predominately available as tablets and capsules that may pose swallowing difficulties for some patients. Using a variety of sources (the primary literature, pharmaceutical package inserts, and requests for unpublished data from drug manufacturers), available evidence on the bioavailability of ARV medications after disruption of the capsule or tablet matrix was reviewed; information on alternative formulations of ARV agents was also assessed. With several ARV agents, disruption of the solid oral dosage form by crushing, chewing, or breaking tablets or opening capsules prior to ingestion has been shown to result in altered bioavailability or pharmacokinetics and thus the potential for incomplete virological suppression, increased adverse effects, and suboptimal health outcomes., Conclusion: Of the 33 single-agent ARV medications and combination ARV products in five classes available at the time of review, approximately half exist as powders, liquids, injectables, or chewable or dissolvable tablets. If alternative ARV formulations or administration methods are used, close monitoring for achievement of virological and immunologic success and potential toxicities is recommended., (Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)
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- 2015
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12. A standardized rubric to evaluate student presentations.
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Peeters MJ, Sahloff EG, and Stone GE
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- Educational Measurement, Humans, Reproducibility of Results, Education, Pharmacy methods, Models, Statistical, Students, Pharmacy
- Abstract
Objective: To design, implement, and assess a rubric to evaluate student presentations in a capstone doctor of pharmacy (PharmD) course., Design: A 20-item rubric was designed and used to evaluate student presentations in a capstone fourth-year course in 2007-2008, and then revised and expanded to 25 items and used to evaluate student presentations for the same course in 2008-2009. Two faculty members evaluated each presentation., Assessment: The Many-Facets Rasch Model (MFRM) was used to determine the rubric's reliability, quantify the contribution of evaluator harshness/leniency in scoring, and assess grading validity by comparing the current grading method with a criterion-referenced grading scheme. In 2007-2008, rubric reliability was 0.98, with a separation of 7.1 and 4 rating scale categories. In 2008-2009, MFRM analysis suggested 2 of 98 grades be adjusted to eliminate evaluator leniency, while a further criterion-referenced MFRM analysis suggested 10 of 98 grades should be adjusted., Conclusion: The evaluation rubric was reliable and evaluator leniency appeared minimal. However, a criterion-referenced re-analysis suggested a need for further revisions to the rubric and evaluation process.
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- 2010
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13. Evaluating the validity and reliability of a modified survey to assess patient satisfaction with mail-order and community pharmacy settings.
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Pinto SL, Sahloff EG, and Ramasamy A
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- Cross-Sectional Studies, Data Collection, Factor Analysis, Statistical, Humans, Reproducibility of Results, HIV Infections drug therapy, Patient Satisfaction, Pharmacies, Postal Service
- Abstract
The level of patient-pharmacist interactions and services provided varies across different distribution methods and could affect patient satisfaction with services. Determining patient satisfaction with these medication distribution methods is important for improving care of chronic disease patients. This study evaluated the validity and reliability of a modified survey to assess patient satisfaction with mail-order and community pharmacy settings. Exploratory cross-sectional design using a convenience sample of HIV-infected patients at a university clinic was used. Satisfaction scale was modified from previously validated instrument resulting in 21 items on the final survey. Data collection occurred for 7 months, and 178 surveys were completed. An exploratory factor analysis was conducted using principal components and varimax rotation. Reliability and item analyses were conducted. Factor analysis resulted in a 2-factor solution, namely "satisfaction with the efficient functioning of the pharmacy" and "satisfaction with the managing therapy role of the pharmacist," respectively. Cronbach's alpha for factors 1 and 2 with mail-order were .951 and .795, for independent were .977 and .965, and for chain were .841 and .823. The study provides a valuable tool to assess patient satisfaction with pharmacy services provided through different distribution methods.
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- 2010
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14. Maraviroc: a coreceptor CCR5 antagonist for management of HIV infection.
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Yost R, Pasquale TR, and Sahloff EG
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- Animals, Cyclohexanes pharmacology, Disease Management, HIV Fusion Inhibitors pharmacology, HIV Infections metabolism, HIV-1 drug effects, Humans, Maraviroc, Receptors, CCR5 physiology, Triazoles pharmacology, CCR5 Receptor Antagonists, Cyclohexanes therapeutic use, HIV Fusion Inhibitors therapeutic use, HIV Infections drug therapy, Triazoles therapeutic use
- Abstract
Purpose: The mechanism of action, pharmacology, pharmacokinetics, clinical efficacy, drug interactions, adverse effects, dosage and administration, cost, and role in therapy of maraviroc are reviewed., Summary: Maraviroc is the first CCR5 coreceptor antagonist to receive marketing approval from the Food and Drug Administration (FDA) for the treatment of CCR5-tropic human immunodeficiency virus (HIV) infection as part of an optimized antiretroviral regimen in treatment-experienced patients. As 50% or more of treatment-experienced patients may be infected with CXCR4-tropic virus, a tropism assay should be performed before initiating maraviroc therapy. The majority of evidence supporting maraviroc's use comes from two studies of HIV-infected, treatment-experienced patients. Pooled analysis from these two studies revealed that twice-daily maraviroc decreased HIV-1 RNA by 1.84 log copies/mL, compared with 0.78 log copy/mL with placebo. Forty-six percent of subjects attained an HIV-1 RNA concentration of <50 copies/mL, compared with only 17% with placebo. In a trial of treatment-naive HIV-infected individuals, maraviroc failed to show noninferiority to efavirenz. Maraviroc is metabolized by cytochrome P-450 isoenzyme 3A4 and is subject to interactions with inhibitors and inducers of that isoenzyme, such as the protease inhibitors (except tipranavir), efavirenz, and rifampin. Resistance has been reported with maraviroc, but specific mechanisms are still poorly understood. The most common adverse effects reported with maraviroc were diarrhea, nausea, fatigue, and headache., Conclusion: Available data support the use of maraviroc, the first CCR5 antagonist to receive FDA marketing approval, as part of an optimized antiretroviral regimen in treatment-experienced patients infected with CCR5-tropic HIV.
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- 2009
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15. Clinical outcomes associated with concomitant use of atazanavir and proton pump inhibitors.
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Sahloff EG and Duggan JM
- Subjects
- Adult, Atazanavir Sulfate, Drug Interactions, Drug Therapy, Combination, Female, HIV Infections blood, HIV Infections drug therapy, HIV-1, Humans, Male, Middle Aged, Oligopeptides blood, Proton Pumps blood, Pyridines blood, Retrospective Studies, Treatment Outcome, Oligopeptides administration & dosage, Proton Pump Inhibitors, Pyridines administration & dosage
- Abstract
Background: Pharmacokinetic studies have shown that the concomitant use of atazanavir and proton pump inhibitors (PPIs) decreases atazanavir plasma concentrations. Data describing clinical outcomes associated with this drug interaction are limited., Objective: To describe the clinical outcomes, in terms of viral load (VL) suppression, associated with the concurrent use of ritonavir-boosted or unboosted atazanavir and PPIs., Methods: A retrospective chart review of 301 HIV-positive adults attending an Ohio infectious diseases clinic was performed to identify patients prescribed atazanavir, with or without ritonavir, and a PPI. The primary outcome was achievement/maintenance of VL less than 400 copies/mL for 2 or more months during concomitant atazanavir and PPI therapies. Data collected included VL and CD4+ cell count at initiation of coadministered atazanavir and PPIs, genotype/phenotype, prior protease inhibitor experience, length of concurrent atazanavir/PPI therapy, and adherence., Results: Twelve patients met inclusion criteria. PPIs and dosing regimens varied among subjects. Five of the subjects had a VL less than 400 copies/mL at initiation of atazanavir, with or without ritonavir, which was maintained during concurrent atazanavir and PPI therapy. Four additional subjects initiated protease inhibitor treatment with a VL greater than 400 copies/mL and achieved an undetectable VL while on concurrent PPI therapy. Duration of concurrent therapy ranged from 4 to 23 months in these 9 subjects. Of the 3 patients not maintaining a VL less than 400 copies/mL, 1 achieved that level at 4 months, and all 3 of these subjects showed atazanavir susceptibility during therapy per genotype resistance testing. Subsequently, decreased atazanavir susceptibility was reported in 1 of the 3 patients after 18 months of therapy. Patients not achieving an undetectable VL had known adherence issues., Conclusions: In this case series, 9 of 12 subjects achieved successful virologic outcomes while receiving concurrent atazanavir and PPIs in a real-world environment. In our experience, the interaction between atazanavir and once-daily PPIs is not clinically significant for adherent patients. Concurrent use of these medications could be considered in patients with limited treatment options.
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- 2006
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16. Current issues in the development of a vaccine to prevent human immunodeficiency virus: insights from the society of infectious diseases pharmacists.
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Sahloff EG
- Subjects
- Clinical Trials as Topic, Humans, AIDS Vaccines immunology, HIV Infections immunology, HIV Infections prevention & control, HIV-1 immunology
- Abstract
Infection with the human immunodeficiency virus (HIV) continues to affect millions of people worldwide. Preventive measures have done little to slow the transmission of the virus. Discovery of an effective vaccine to prevent HIV could have a tremendous impact on this global pandemic. However, the complex interactions between HIV and the host immune system have limited the progress in vaccine development. Traditional vaccination strategies have shown little promise. Currently, subunit vaccines, DNA vaccines, recombinant vector vaccines, and prime-boost strategies are being evaluated in clinical trials. Although many breakthroughs have been made in HIV vaccine research, only three candidate HIV vaccines have been studied in phase III clinical trials. The current strategies being investigated in the development of preventive HIV vaccines are reviewed.
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- 2005
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17. Use of highly active antiretroviral therapy in patients with renal insufficiency.
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Duggan JM, Sahloff EG, and Moudgal VV
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- HIV Infections complications, Humans, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, Renal Insufficiency complications
- Abstract
Antiretroviral agents, especially nucleoside reverse transcriptase inhibitors, require significant dosage adjustments in patients who have renal dysfunction and the human immunodeficiency virus (HIV). Some antiretroviral agents and fixed combination preparations are contraindicated in this population. In addition, many preferred antiretroviral regimens may be difficult to administer conveniently in patients with decreased creatinine clearance or in those receiving renal replacement therapies. Some highly active antiretroviral therapy regimens, however, can be used conveniently in patients with HIV and altered renal function.
- Published
- 2005
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18. Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections.
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Martin SJ, Sahloff EG, and Close SJ
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- Clinical Trials as Topic economics, Clinical Trials as Topic statistics & numerical data, Community-Acquired Infections drug therapy, Costs and Cost Analysis methods, Costs and Cost Analysis statistics & numerical data, Fluoroquinolones therapeutic use, Humans, Microbial Sensitivity Tests, Respiratory Tract Infections drug therapy, Community-Acquired Infections economics, Fluoroquinolones economics, Respiratory Tract Infections economics
- Abstract
Several new fluoroquinolones have been marketed since the late 1990s. Fluoroquinolones are an effective treatment for most community-acquired respiratory tract infections, including acute sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. However, other antibiotics, including beta-lactams, macrolides, tetracyclines and trimethoprim-sulfamethoxazole, are also effective against these respiratory infections. From a managed care perspective, it is the subtle differences between the drugs in the eradication of bacterial pathogens, adverse effects, dose regimens, compliance issues, bacterial resistance and cost that determine the best choice for the management of pneumonia, sinusitis or exacerbations of chronic bronchitis. The potential for bacterial resistance is perhaps the only significant barrier to extensive fluoroquinolone use in community-acquired respiratory tract infections. Cost-effectiveness must be balanced with quality care, both from an individual perspective and that of the greater society.
- Published
- 2002
- Full Text
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19. The activity of 14-hydroxy clarithromycin, alone and in combination with clarithromycin, against penicillin- and erythromycin-resistant Streptococcus pneumoniae.
- Author
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Martin SJ, Garvin CG, McBurney CR, and Sahloff EG
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- Clarithromycin analogs & derivatives, Colony Count, Microbial, Drug Combinations, Erythromycin pharmacology, Humans, Microbial Sensitivity Tests, Penicillin Resistance, Anti-Bacterial Agents pharmacology, Clarithromycin pharmacology, Drug Resistance, Multiple physiology, Streptococcus pneumoniae drug effects
- Abstract
There are no data regarding the activity of clarithromycin's active metabolite, 14-hydroxy clarithromycin, against penicillin-intermediate, penicillin-resistant or erythromycin-resistant Streptococcus pneumoniae. Agar dilution MICs were determined for clarithromycin, 14-hydroxy clarithromycin (henceforth called 'metabolite'), azithromycin, erythromycin and clarithromycin/metabolite (2:1 and 1:1 ratio) against 24 penicillin-intermediate and 14 penicillin-resistant strains, including 13 erythromycin-resistant clinical strains and one ATCC strain of S. pneumoniae. The interaction between clarithromycin and its metabolite was determined using an agar chequerboard assay against all isolates, and time-kill tests were performed against five penicillin-intermediate (macrolide-susceptible) and five penicillin-resistant (two macrolide-resistant) strains of S. pneumoniae using all antibiotics alone at simulated peak serum concentrations, and clarithromycin/metabolite in a 2:1 ratio (physiological). MICs were as follows: clarithromycin, 0.008-->64 mg/L; metabolite, 0.015-->64 mg/L; erythromycin, 0.015-->64 mg/L; azithromycin, 0.125-->64 mg/L; clarithromycin/metabolite (1:1 and 2:1 combinations), 0.001-->64 mg/L. The MIC of the clarithromycin/metabolite combination was one or more tube dilution lower than the MIC of clarithromycin in 28 of the isolates tested. In chequerboard testing, 13 strains (seven erythromycin susceptible and six erythromycin resistant) demonstrated synergy, 18 additivity and seven indifference. In time-kill testing, bacterial eradication below detection limits occurred with clarithromycin and metabolite in seven of 10 organisms. The combination of parent and metabolite was more rapidly bactericidal than clarithromycin alone in six of the seven isolates (P = 0.026). The metabolite has potent activity against S. pneumoniae and enhances the activity of the parent compound against this organism. The metabolite's activity must be considered in evaluating clarithromycin in vitro to avoid underestimation of clarithromycin's activity against the pneumococcus.
- Published
- 2001
- Full Text
- View/download PDF
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