Ian R. McNicholl

Valganciclovir: An Advance in Cytomegalovirus Therapeutics

OBJECTIVE: To review the pharmacology, pharmacokinetics, and preliminary clinical data for valganciclovir, a new oral agent for the therapy of cytomegalovirus (CMV) retinitis. DATA SOURCES: Relevant literature was extracted via MEDLINE/PUBMED and searchable abstracts from infectious diseases conferences covering the period from January 1990 to April 2002. Tertiary references provided background information. DATA SYNTHESIS: Current standard treatment for CMV retinitis consists of intravenous therapy, intraocular implant, and intraocular injection. The low bioavailability of oral ganciclovir restricts its use to prophylaxis and maintenance treatment. Oral valganciclovir, recently approved for both induction and maintenance therapy of CMV retinitis, may fill a niche for this disease. CONCLUSIONS: Although only 1 clinical study has been published for valganciclovir, its favorable pharmacokinetic profile, encouraging preliminary efficacy data, ease of administration, and lack of potential catheter-related complications make it a favorable option for the treatment of CMV retinitis in HIV-positive patients.

Polypharmacy, Drug–Drug Interactions, and Potentially Inappropriate Medications in Older Adults with Human Immunodeficiency Virus Infection

To describe the frequency of medication‐related problems in older adults with human immunodeficiency virus (HIV) infection.

Etravirine and Rilpivirine: Nonnucleoside Reverse Transcriptase Inhibitors with Activity Against Human Immunodeficiency Virus Type 1 Strains Resistant to Previous Nonnucleoside Agents

Etravirine and rilpivirine are two new nonnucleoside reverse transcriptase inhibitors (NNRTIs) that have the distinct advantage of being able to be used in patients with exposure to previous NNRTIs (e.g., nevirapine or efavirenz). Etravirine was approved by the United States Food and Drug Administration to be used twice/day in treatment‐experienced patients infected with the human immunodeficiency virus. The approval was based on phase III clinical studies in which 61% of etravirine‐treated patients reached an undetectable viral load of less than 50 copies/ml compared with 40% of patients who received the optimized background regimen. Etravirine was well tolerated with a self‐limiting skin rash being the most common toxicity, reported in 19% of patients. Rilpivirine, a once‐daily NNRTI, is entering phase III studies; the drug appears to be effective against a broad range of NNRTI‐resistant viruses including etravirine‐resistant strains.

Pharmacoeconomic Analysis of Ampicillin-Sulbactam versus Cefoxitin in the Treatment of Intraabdominal Infections

We conducted a retrospective pharmacoeconomic analysis of a prospective, multicenter, double‐blind, randomized, controlled trial comparing the β‐lactamase inhibitor combination ampicillin‐sulbactam (96 patients) and the cephalosporin cefoxitin (101) in the treatment of intraabdominal infections. An institutional perspective was adopted for the analysis. The primary outcomes of interest were cure and failure rates, development of new infection, and antibiotic‐related adverse events. Epidemiologic data pertaining to outcomes was retrieved primarily from the trial, although results of other published studies were taken into consideration through extensive sensitivity analyses. Data pertaining to potential resource use and economic impact were retrieved mainly from the University Health Consortium and hospital‐specific sources. When considering only costs associated with drug acquisition through cost‐minimization analysis, a potential savings of

Coinfection with human immunodeficiency virus and hepatitis C virus: challenges and therapeutic advances. Insights from the Society of Infectious Diseases Pharmacists.

37.24/patient may be realized with ampicillin‐sulbactam relative to cefoxitin based on an average 7‐day regimen. Outcome data collected for the entire hospitalization during the trial revealed an approximately 9% greater frequency of failure with cefoxitin relative to ampicillin‐sulbactam. When considering all outcomes of interest in the initial base‐case analysis, a potential cost savings of approximately

Active Immunization in HIV-infected Patients

890/patient may be realized with ampicillin‐sulbactam relative to cefoxitin. In assessing the impact of the significant variability in probability and cost estimates, Monte Carlo analysis revealed a savings of

A Pharmacist‐Led Program to Evaluate and Reduce Polypharmacy and Potentially Inappropriate Prescribing in Older HIV‐Positive Patients

425/patient for ampicillin‐sulbactam over cefoxitin (95% CI

Drug interactions among the antiretrovirals

618–1516). Given the model assumptions, our analysis suggests a 78% certainty level that savings will be experienced when ampicillin‐sulbactam is chosen over cefoxitin.

Does Once-Daily Etravirine Have a Role in the Management of HIV-1 Infection?

In the United States, approximately 30% of all human immunodeficiency virus (HIV)-positive patients are also infected with hepatitis C virus (HCV). Both viruses share similar routes of transmission. Unlike HIV or hepatitis B virus, HCV is curable if treated and the patient achieves a sustained virologic response. The impact of coinfection includes greater morbidity and mortality, with higher rates of opportunistic disease, development of cirrhosis, and death. The standard of treatment for HIV-HCV coinfection is similar to that for HCV monoinfection and consists of pegylated interferon alfa and ribavirin. As with HCV monoinfection, the best predictor of response to therapy for HIV-HCV coinfection is infection with an HCV genotype other than genotype 1 or 4. Adherence to treatment is critical for improving response to HCV therapy. However, considerable toxicities are associated with pegylated interferon alfa and ribavirin and pose particular problems in the coinfected patient. Coinfected patients are more likely to experience significant weight loss with HCV therapy. Neutropenia and anemia are both common laboratory abnormalities that necessitate dosage reductions and are concerns for development of acquired immunodeficiency syndrome-defining events. The effect of CD4+ cell count has been evaluated both as a factor in response to HCV therapy and in stratification of risk for infection. Immunosuppression is not a contraindication to HCV therapy, although CD4+ counts above 350 cells/mm3 are associated with increased response rates in patients with HCV genotype 1 coinfection. Antiretroviral therapy does need to be adjusted to minimize adverse effects. Concomitant use of zidovudine is contraindicated because of its profound exacerbation of bone marrow suppression. The use of didanosine is also not indicated during HCV therapy because of the risks of hepatic decompensation. Controversy exists regarding the use of abacavir. Newer agents for HCV include the protease inhibitors telaprevir and boceprevir. Although results with the protease inhibitors are highly encouraging, their effects in coinfected patients have not been evaluated. Treatment for HCV in patients with HIV poses potential obstacles to success, but the benefits of viral eradication warrant the challenge of therapy.In the United States, approximately 30% of all human immunodeficiency virus (HIV)‐positive patients are also infected with hepatitis C virus (HCV). Both viruses share similar routes of transmission. Unlike HIV or hepatitis B virus, HCV is curable if treated and the patient achieves a sustained virologic response. The impact of coinfection includes greater morbidity and mortality, with higher rates of opportunistic disease, development of cirrhosis, and death. The standard of treatment for HIV‐HCV coinfection is similar to that for HCV monoinfection and consists of pegylated interferon alfa and ribavirin. As with HCV monoinfection, the best predictor of response to therapy for HIV‐HCV coinfection is infection with an HCV genotype other than genotype 1 or 4. Adherence to treatment is critical for improving response to HCV therapy. However, considerable toxicities are associated with pegylated interferon alfa and ribavirin and pose particular problems in the coinfected patient. Coinfected patients are more likely to experience significant weight loss with HCV therapy. Neutropenia and anemia are both common laboratory abnormalities that necessitate dosage reductions and are concerns for development of acquired immunodeficiency syndrome‐defining events. The effect of CD4+ cell count has been evaluated both as a factor in response to HCV therapy and in stratification of risk for infection. Immunosuppression is not a contraindication to HCV therapy, although CD4+ counts above 350 cells/mm3 are associated with increased response rates in patients with HCV genotype 1 coinfection. Antiretroviral therapy does need to be adjusted to minimize adverse effects. Concomitant use of zidovudine is contraindicated because of its profound exacerbation of bone marrow suppression. The use of didanosine is also not indicated during HCV therapy because of the risks of hepatic decompensation. Controversy exists regarding the use of abacavir. Newer agents for HCV include the protease inhibitors telaprevir and boceprevir. Although results with the protease inhibitors are highly encouraging, their effects in coinfected patients have not been evaluated. Treatment for HCV in patients with HIV poses potential obstacles to success, but the benefits of viral eradication warrant the challenge of therapy.

Book Review: The Hands-on-Guide to Clinical Pharmacology, 3rd Edition:

Patients infected with human immunodeficiency virus (HIV) are at risk for various viral and bacterial infections. Active immunization with currently available vaccines may reduce the risk of some vaccine‐preventable diseases in this population. Based on available data, most vaccines used in the United States are safe in HIV‐infected adults and children. Their clinical efficacy in these individuals is not well defined, although it appears that patients in the earlier stages of infection are more likely to mount a protective antibody response than those in the later stages. Current guidelines for vaccination in HIV‐infected children and adults in the United States have been recommended by the Advisory Committee on Immunization Practices.