Eric G. Sahloff

Exogenous Cushing Syndrome with Inhaled Fluticasone in a Child Receiving Lopinavir/Ritonavir

Objective: To describe a case of Cushing syndrome in a child during concurrent use of inhaled fluticasone propionate, nasal mometasone, and a highly active antiretroviral regimen including lopinavir/ritonavir. Case Summary: A 9-year-old boy with HIV infection and asthma developed moon fades, increased facial hair, and increased weight after fluticasone propionate inhalation (1 puff; 220 μg) therapy was begun. His antiretroviraI regimen contained the protease inhibitor combination lopinavir/ritonavir at a dose of 216/54 mg twice daily, and he had been stable for the previous 5 years. He had also been receiving intranasal mometasone for 11 months for the management of allergic rhinitis. Serum Cortisol and adrenocorticotropic hormone levels were consistent with adrenal suppression, These physical findings and symptoms and laboratory values normalized after discontinuation of the fluticasone propionate. The Naranjo probability scale indicated that a probable interaction occurred between lopinavir/ritonavir and fluticasone propionate, loading to subsequent adrenal suppression. Discussion: Protease inhibitors are associated with numerous drug interactions due to inhibition of the CYP3A4 isoenzyme. Pharmaceutical agents used to treat comorbidities in HIV-infected individuals often can interact with protease inhibitors, leading to toxic drug concentrations or untoward effects. Inhaled corticosteroids such as fluticasone propionate are often necessary to treat asthma in young children and are metabolized by CYP3A4. Interactions between protease inhibitors and inhaled fluticasone propionate have been reported in the adult population, but reports are limited in the pediatric literature. Conclusions: This case raises awareness of the interaction between fluticasone propionate and lopinavir/ritonavir and adverse effects in children receiving both medications.

Clinical Outcomes Associated with Concomitant Use of Atazanavir and Proton Pump Inhibitors

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.

Evaluation and cost assessment of fluoroquinolones in community-acquired respiratory infections

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 β-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.

Alternative antiretroviral therapy formulations for patients unable to swallow solid oral dosage forms

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.

Current issues in the development of a vaccine to prevent human immunodeficiency virus : Insights from the society of infectious diseases pharmacists

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.

Evaluation of Serum Creatinine Changes With Integrase Inhibitor Use in Human Immunodeficiency Virus-1 Infected Adults.

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.

Evaluating the validity and reliability of a modified survey to assess patient satisfaction with mail-order and community pharmacy settings.

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.

Gingival Hypertrophy Associated with Amlodipine Use in an HIV-Infected Woman

Objective: To report the case of a 46-year-old woman with HIV infection who developed gingival hypertrophy while taking amlodipine for hypertension and review the literature discussing gingival hypertrophy associated with amlodipine and other calcium channel blockers. Case Summary: A 46-year-old HIV-infected female was taking amlodipine 5 mg daily to manage hypertension. After 4 1/2 years of exposure to amlodipine, the patient presented with new-onset gingival hypertrophy. Concurrent medications included atazanavir, ritonavir, tenofovir/emtricitabine, a multivitamin, and ibuprofen and tramadol as needed. Amlodipine was discontinued and lisinopril was initiated to manage hypertension. Resolution of gingival hypertrophy was noted at 3- and 12-month follow-up visits. Discussion: Drug-induced gingival hypertrophy has been associated with anticonvulsants, immunosuppressants, and calcium channel blockers. Cases of gingival hypertrophy are uncommon, especially after such extended exposure. The Naranjo probability scale classified the reaction as probable. Discontinuation of amlodipine led to resolution of gingival hypertrophy. Conclusions: Patients with new-onset gingival hypertrophy should have a complete medication review to identify potential causative agents. Development of gingival hypertrophy may present acutely or with extended exposure. Resolution of gingival hypertrophy generally occurs with discontinuation of the inciting agent.

Use of Highly Active Antiretroviral Therapy in Patients with Renal Insufficiency

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.

Clinical Outcomes Associated With Once-Daily Ritonavir-Boosted Darunavir Plus Tenofovir/Emtricitabine in HIV-Infected Patients Harboring at Minimum a M184V/I Resistance Mutation

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.