HIV non-occupational postexposure prophylaxis in a Canadian province: treatment completion and follow-up testing.

Provincial guidelines for HIV non-occupational postexposure prophylaxis (NPEP) were implemented on January 2005 in Alberta, Canada. Human immunodeficiency virus (HIV) NPEP was provided free of charge following approval by a medical officer of health. Between 1 January 2005 and 30 June 2007, 174 individuals were prescribed NPEP; 135 (78%) were women with a median age of 24 years. Sexual assaults accounted for 68% of exposures. NPEP was completed in 49% of cases. Individuals who completed NPEP were less likely to have been exposed by sexual assault (P = 0.04) and more likely to have received HIV follow-up testing (P = 0.03).Individuals who received at least one HIV follow-up test were older (P = 0.03) and more likely to have been exposed percutaneously (P = 0.003). Those who received no follow-up testing were less likely to have filled an NPEP prescription (P = 0.0001). New strategies are required to improve follow-up of individuals receiving NPEP, especially younger persons or sexual assault survivors.

Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature.

OBJECTIVE: The purpose of this article is to provide a systematic overview of the literature on adrenal suppression and Cushing's syndrome secondary to an interaction between inhaled/intranasal fluticasone and ritonavir. The clinical presentation, diagnosis and management will be discussed. METHODS: A literature search using Medline and EMBASE and a search of abstracts of the three previous years of major HIV-related conferences were carried out. RESULTS: There were 25 cases (15 adult and 10 paediatric) of significant adrenal suppression secondary to an interaction between ritonavir and inhaled fluticasone, and three cases involving ritonavir and intranasal fluticasone. Cases with other steroids were not reported; however, there were cases of adrenal suppression with itraconazole [also a potent cytochrome p (CYP) 3A4 inhibitor] and inhaled budesonide. Clinicians need to differentiate between antiretroviral-induced lipodystrophy syndrome and iatrogenic Cushing's syndrome secondary to glucocorticoid use. Long-term fluticasone and ritonavir should be avoided. If ritonavir is required, another inhaled steroid such as low-dose budesonide or beclomethasone can be used cautiously. Upon discontinuation of inhaled corticosteroids, close monitoring for symptoms of adrenal insufficiency is warranted. The need for steroid replacement therapy at physiological doses should be assessed. CONCLUSIONS: The combination of ritonavir and fluticasone should be avoided. Budesonide, beclomethasone, triamcinolone and flunisolide appear to be safer options.

Impaired emotional facial expression recognition in alcoholism compared with obsessive-compulsive disorder and normal controls.

Emotional facial expression (EFE) decoding skills have been shown to be impaired in recovering alcoholics (RA). The aim of the present study is to replicate these results and to explore whether these abnormalities are specific to alcoholism using two control groups: non-patient controls (NC) and patients with obsessive-compulsive disorder (OC). Twenty-two alcoholic patients at the end of their detoxification process (RA) were compared to 22 OC and 22 NC matched for age, sex and education level. They were presented with 12 photographs of facial expressions portraying different emotions: happiness; anger; and fear. Each emotion was displayed with mild (30%) and moderate (70%) intensity levels. Each EFE was judged on 8 scales labeled happiness, sadness, fear, anger, disgust, surprise, shame and contempt. For each scale, subjects rated the estimated intensity level. RA were less accurate in EFE decoding than OC and NC, particularly for anger and happiness expressions. RA overestimated the emotional intensity for mild intensity level expressions compared with both OC and NC while no significant differences emerged for moderate intensity level expressions. Deficits in EFE decoding skills seem to be specific to RA when compared with OC. Comparison with other psychopathological groups is still needed. Possible consequences of EFE decoding deficits in RA include distorted interpersonal relationships.

Enhanced penetration of indinavir in cerebrospinal fluid and semen after the addition of low-dose ritonavir.

OBJECTIVE: Penetration of antiretroviral drugs into anatomical HIV-1 reservoirs such as the male genital tract and the central nervous system is important. Data on indinavir (IDV) concentrations in seminal plasma are lacking and IDV concentrations in cerebrospinal fluid are at best borderline. DESIGN: Thirteen patients were treated with zidovudine (or stavudine), lamivudine, abacavir, nevirapine and IDV (1000 mg three times daily). When nevirapine led to low IDV concentrations, IDV was changed into the combination IDV/ritonavir (RTV) 800/100 mg twice daily to improve the pharmacokinetic profile of IDV. METHODS: A serum pharmacokinetic profile, a semen sample and a cerebrospinal fluid sample were collected at weeks 8, 24, 48 and 72. RESULTS: Addition of RTV increased the median IDV trough concentration in serum from 65 to 336 ng/ml (P = 0.005). Median IDV concentration in seminal plasma increased from 141 to 1634 ng/ml (P = 0.002) (n = 9) and in cerebrospinal fluid from 39 (n = 12) to 104 (n = 7) ng/ml (P < 0.001). In six patients with samples collected both before and after the addition of RTV, the IDV concentration in seminal plasma increased 8.2 times [95% confidence interval (CI) 5.2-11.6], and in cerebrospinal fluid 2.4 times (95% CI 1.8-3.9). CONCLUSIONS: IDV penetrates well into the male genital tract. The addition of low-dose RTV not only increases IDV concentrations in serum but also in seminal plasma and cerebrospinal fluid, thereby probably improving the potency of the regimen in these anatomical HIV reservoirs. Higher serum trough levels alone can not sufficiently explain the observed increases in seminal plasma and cerebrospinal fluid concentrations. Inhibition of P-glycoprotein-mediated transport by RTV might be an additional mechanism.

Hospitalization due to adverse drug reactions and drug interactions before and after HAART.

OBJECTIVE: To characterize and compare the rates of adverse drug reactions (ADRs) and interactions on admission in two, one-year periods: pre-highly active antiretroviral therapy (HAART) (phase 1) and post-HAART (phase 2). DESIGN: Retrospective chart review. SETTING: University-affiliated tertiary care centre. POPULATION STUDIED: HIV-positive patients admitted to hospital. MAIN RESULTS: In phase 1, 436 of 517 admissions, and, in phase 2, 323 of 350 admissions were analyzed. Over 92% of patients were male, with a mean age of 38 years. Significant differences (P<0.05) in the mean length of stay (12.08 versus 10.02 days), the CD4 counts (99.25 versus 129.45) and the number of concurrent diseases (4.20 versus 3.63) were found between phase 1 and 2, respectively. The mean number of medications taken (5.52 versus 5.94) and the rates of hospitalization with ADRs (20.4% versus 21.4%) or interactions (2.5% versus 2.16%) were similar between the two phases. Antiretrovirals were more common in ADR admissions post-HAART (21.3% versus 36.2%), while antiparasitics, psychotherapeutics and antineoplastics were more common pre-HAART. Other classes of drugs involved in both phases were sulphonamides, narcotics, ganciclovir, foscarnet, antimycobacterials and antifungals. ADR causality was possible or probable in more than 80% of cases. Over 60% of ADRs were grades 3 to 4, and about 85% were either the main or contributing reason for admission. About 65% of patients had at least partial recovery at the time of discharge. In phases 1 and 2, 8.9% and 2.9% of admissions,respectively, with ADRs were fatal. CONCLUSIONS: Although hospitalizations with ADRs and interactions were similar in both phases, HAART therapy has had a significant impact on the incidence and nature of ADRs at St Michael's Hospital, Wellesley Central Site, Toronto, Ontario.

Significant interactions with new antiretrovirals and psychotropic drugs.

OBJECTIVE: To provide an update on relevant antiretroviral interactions and psychotropic medications for healthcare practitioners managing complex HIV-related pharmacotherapy. DATA SOURCES: Information was retrieved via a MEDLINE search (January 1966-September 1998) using MeSH headings human immunodeficiency virus, drug interactions, psychiatry, psychotropics, psychiatric illness, and names of medications commonly prescribed for the management of HIV infection. Abstracts of international and national conferences (until February 1999), review articles, textbooks, and references of all articles also were searched. STUDY SELECTION AND DATA EXTRACTION: Literature on pharmacokinetic interactions was considered for inclusion. Pertinent information was selected and summarized for discussion. In the absence of specific data, pharmacokinetic and pharmacodynamic properties were considered in order to predict the likelihood of potential drug interactions. DATA SYNTHESIS: All protease inhibitors and nonnucleoside reverse transcriptase inhibitors are substrates of the cytochrome P450 system and possess enzyme-inhibiting and/or -inducing properties. Psychotropic medications also possess similar metabolic characteristics and may interact with antiretrovirals. Modifications in drug selection, dose, or dosing regimen may be needed to ensure adequate antiretroviral concentrations and thus minimize the risk of incomplete viral suppression and/or development of drug resistance. In the absence of specific data, consideration of metabolic characteristics may assist practitioners in predicting the likelihood of possible interactions. RESULTS: The incidence and implications of antiretroviral drug interactions are reviewed. Practical management strategies are also discussed. Comprehensive tables on clinically significant interactions with antiretroviral combinations and with psychiatric medications are provided. CONCLUSIONS: Given the increasing use of multiple-drug therapy, the potential for drug interactions is extremely high. Drug interactions may lead to undesirable outcomes including subtherapeutic drug concentrations and risk of antiretroviral resistance. Practitioners need to consider pharmacokinetic, pharmacologic, therapeutic, and adherence factors when managing interactions with complex antiretroviral therapy.

Rapid quantification of indinavir in human plasma by high-performance liquid chromatography with ultraviolet detection.

A rapid, sensitive and specific high-performance liquid chromatography (HPLC) procedure for the quantification of indinavir, a potent human immunodeficiency virus (HIV) protease inhibitor, in human plasma is described. Following C18 solid-phase extraction, indinavir was chromatographed on a reversed-phase C8 column using a simple binary mobile phase of phosphate buffer-acetonitrile (60:40, v/v). UV detection at 210 nm led to an adequate sensitivity without interference from endogenous matrix components. The limit of quantification was 25 ng/ml with a 0.1 ml plasma sample. The standard curve was linear across the range from 25 to 2500 ng/ml with an average recovery of 91.4%. The mean relative standard deviations for concentrations within the standard curve ranged between 1.4 and 9.7%. Quality control standards gave satisfactory intra- and inter-assay precision (R.S.D. from 3.5 to 15.8%) and accuracy within 15% of the nominal concentration. Sample handling experiments, including HIV heat inactivation, demonstrated analyte stability under expected handling processes. The assay is suitable for the analysis of samples from adult and pediatric patients infected with HIV.

Management of drug interactions in patients with HIV.

OBJECTIVE: To provide a complication of relevant information on drug interactions to assist healthcare practitioners in managing complex HIV-related pharmacotherapy. DATA SOURCES: Information was retrieved via a MEDLINE search (January 1966-December 1996) using MeSH headings "human immunodeficiency virus," "drug interactions," and names of medications commonly prescribed for the management of HIV infection and related opportunistic infections. Abstracts of international and national conferences, review articles, textbooks, and references of all articles were also searched. STUDY SELECTION AND DATA EXTRACTION: All literature on pharmacokinetic or pharmacodynamic interactions was considered for inclusion. Pertinent information, as assessed by the authors, was selected and summarized for discussion. DATA SYNTHESIS: Drug disposition and/or pharmacologic effect may be affected either by HIV-related physiologic changes or by the presence of concomitant drug therapy. Modifications in drug selection, dosage, dosing regimen, or route of administration may be needed to avoid or manage drug-disease, drug-drug, or drug-food interactions. Management options may depend on the mechanism and the clinical significance of the interaction, the availability of therapeutic alternatives, patient convenience, and cost restrictions. In the absence of specific data, consideration of pharmacokinetic and pharmacodynamic characteristics to assist practitioners in predicting the likelihood of possible interactions was included. RESULTS: A comprehensive table of clinically significant drug interactions is provided. Drug interaction principles and practical management strategies are also discussed. CONCLUSIONS: The potential for drug interactions is extremely common, given the increasing complexity of managing patients infected with HIV. To avoid compromising therapeutic efficacy or increasing drug toxicity, practitioners need to be aware of potential interactions and are encouraged to use a systematic approach when managing patient drug therapy.

Pharmacists' provision of continuity of care to patients with human immunodeficiency virus infection.

A pharmacy program for providing continuity of care to patients infected with human immunodeficiency virus (HIV) is described. The program was implemented at three practice sites in Toronto: a tertiary care teaching hospital; an outpatient community pharmacy that is part of the hospital; and an ambulatory care clinic affiliated with the hospital. An HIV pharmacy practice was established at the hospital in 1993. The community pharmacy serves at least 30% of the HIV-infected patients in Ontario who are receiving antiretrovirals; patient counseling is emphasized. The ambulatory care clinic's HIV program was established in 1994; the pharmacist sees patients at the clinic or in their homes. To address the need for greater continuity of care, the following issues were addressed: workload involved in providing pharmaceutical care to HIV-infected patients, establishing patient pharmacy profiles common to the three sites, streamlining communication among the sites, creating a process for identifying patient problems in the community setting, collaborating on research and projects, and forging links with other pharmacists caring for HIV-infected patients. The program has enhanced the ability of pharmacists to make informed recommendations and care plans, increased patient follow-up, improved cross-coverage of patients in the absence of an HIV pharmacist, increased sharing of drug information, and led to joint collaboration on projects. A pharmacy program to serve HIV-infected patients was implemented at three sites and successfully integrated under a continuity-of-care model.

The role of ganciclovir for the management of cytomegalovirus retinitis in HIV patients: Pharmacological review and update on new developments.

OBJECTIVE: To review the pharmacology and pharmacokinetics of intravenous, oral and intraocular ganciclovir, and to discuss the role of these various formulations in the management of cytomegalovirus (CMV) retinitis in AIDS patients. DATA SOURCES: A MEDLINE search (1987 through November 1995) of English-language literature using the main medical subject headings 'ganciclovir' and 'cytomegalovirus', and the subheading 'acquired immunodeficiency syndrome'. Relevant articles were also selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology and human immunodeficiency virus were screened for additional data. STUDY SELECTION AND DATA EXTRACTION: All articles and abstracts discussing the use of ganciclovir for the management or prophylaxis of CMV retinitis in AIDS patients were considered for inclusion. Pertinent information, as judged by the authors, was selected and synthesized for discussion. DATA SYNTHESIS: Ganciclovir has demonstrated virustatic activity against CMV, and is often administered 5 mg/kg intravenously every 12 h as first-line therapy for CMV retinitis. Intravenous maintenance therapy at 5 mg/kg daily is usually effective at delaying retinitis progression for approximately 60 to 70 days. Neutropenia and thrombocytopenia are observed frequently, often necessitating interruption or discontinuation of therapy. Local drug administration may delay disease progression even further, and may be considered for patients who are intolerant to or failing intravenous therapy. However, systemic ganciclovir should be encouraged to reduce the risk of developing contralateral eye or end-organ CMV disease. Oral ganciclovir at 1 g tid is almost as effective as intravenous ganciclovir 5 mg/kg/day in delaying retinitis progression and is associated with fewer line-related complications. Absorption, drug interactions, cost and compliance should also be considered. CONCLUSIONS: Until recently, ganciclovir was available only for intravenous use. Recent developments allow for intraocular and oral administration of this agent. A clear understanding of the advantages and disadvantages of these new formulations is required in order to select the most appropriate product for managing CMV retinitis in AIDS patients.

Pancreatitis during intravenous pentamidine therapy in an AIDS patient with prior exposure to didanosine.

OBJECTIVE: To report a case of an HIV-positive man who received sequential didanosine and pentamidine treatment and subsequently developed acute clinical pancreatitis. CASE SUMMARY: In June 1992 didanosine 200 mg po bid was initiated in a 30-year-old man with AIDS. After a 22-week course of didanosine, the patient was hospitalized and didanosine was discontinued on day 4. The patient then received 8 days of treatment for a presumed Pneumocystis carinii pneumonia (PCP) with pentamidine 4 mg/kg/d iv. As the patient responded clinically to therapy, he was discharged home to complete a 21-day course of pentamidine. On day 14 of therapy, the patient experienced nausea, vomiting, diarrhea, fatigue, and was hypotensive. The dosage of pentamidine was reduced by 50 percent. After receiving 18 doses of pentamidine, treatment was discontinued, as symptoms had worsened and serum amylase and lipase concentrations were elevated. The patient was hospitalized and the diagnosis of acute clinical pancreatitis was made. After a 21-day hospitalization, the patient was discharged home in fair condition on hyperalimentation. DISCUSSION: Potential causes of pancreatitis, including opportunistic infections, neoplasms, and drugs, are discussed. The most probable factors associated with pancreatitis in our patient are didanosine and pentamidine therapy. CONCLUSIONS: As our patient developed pancreatitis following sequential administration of didanosine and pentamidine, it would be prudent to monitor for signs and symptoms of pancreatitis in similar cases. In addition, didanosine should be discontinued during and for one week following treatment of PCP when pentamidine is used.

First-pass radionuclide angiographic studies of left ventricular function with technetium-99m-teboroxime, technetium-99m-sestamibi and technetium-99m-DTPA.

Technetium-99m-teboroxime (BATO) and 99mTc-sestamibi (MIBI) may provide the opportunity for first-pass evaluation of left and right ventricular function at rest and exercise in conjunction with myocardial perfusion scintigraphy. This study examined the results of age- and gender-matched patients with clinically normal left ventricular function who underwent resting first-pass studies with BATO (n = 25), MIBI (n = 25) and DTPA (n = 25). There were no significant differences between the observed first-pass tracer kinetics or clinical results of MIBI and DTPA. However, there was significantly greater first-pass pulmonary uptake of BATO compared with either MIBI or DTPA. This resulted in five clinically important differences in the BATO FPRNA images: (1) greater background during the levophase of the tracer transit, (2) prolongation of the measured mean pulmonary transit time, (3) lower raw and final ejection fractions, (4) obscured left ventricular border definition resulting in larger geometrically derived left ventricular volumes and (5) poorer image detail and quality which compromised functional image and regional wall motion interpretation. This study suggests that further refinement of the first-pass methodology, particularly with regard to methods of background subtraction, is needed to obtain quality FPRNA results with BATO. However, for the purposes of left ventricular function analysis with FPRNA, MIBI and DTPA are interchangeable.