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Biomedical subjects

Peter J Piliero

Publications and source records attributed to Peter J Piliero.

26 records · Page 2Linked to original sources

Atazanavir: a novel HIV-1 protease inhibitor.

The introduction of HIV-1 protease inhibitors in 1995 ushered in the era of highly active antiretroviral therapy. For the first time, inhibition of two key enzymes responsible for HIV replication, reverse transcriptase and protease, was possible. The combination of two nucleoside reverse transcriptase inhibitors with a single protease inhibitor proved highly effective at reducing viral burden. In resource-rich countries where such combination therapy is readily available, dramatic reductions in HIV-related morbidity and mortality have been seen. However, long-term use of highly active antiretroviral therapy has led to several issues, including development of drug resistance and metabolic complications. Atazanavir (formerly BMS-232632), a novel azapeptide protease inhibitor, is a potent protease inhibitor that is not associated with significant dyslipidaemia as seen with other protease inhibitors. In this review, the current standard approach to the treatment of HIV in the US will be discussed as background to understand the potential utility of this new antiretroviral agent.

Animals↗

Case report. Hepatitis B virus and HIV coinfection.

Coinfection with HIV and hepatitis B virus (HBV) is more common than that with HIV and hepatitis C virus (HCV), although more attention has been given to HCV coinfection as a result of its higher frequency of chronic disease. Natural history studies with HIV-HCV coinfection have also shown more rapid progression of liver disease, and end-stage liver disease due to hepatitis C is now a leading cause of death in HIV-infected patients. Like HCV infection, HBV infection can also be associated with significant morbidity and mortality in patients with HIV infection. Fortunately, treatment options of hepatitis B are expanding and may have a clinical impact on slowing disease progression. A case study of a patient with severe HBV-HIV coinfection is presented to illustrate what is known about this increasingly problematic disease state.

Antiviral Agents↗

An assessment of herbal therapy use, adherence and utilization of pharmacy services in HIV clinics.

OBJECTIVE: To assess herbal therapy use, adherence to antiretroviral therapy (ART) and pharmacy service utilization in two HIV clinics using a prospective questionnaire-based assessment. RESULTS: Seventy-six patients completed the questionnaire. Twenty-six patients (34%) reported using at least one herbal therapy; 14 (54%) reported this to their provider. Providers correctly predicted herbal therapy use in 10 (38%) patients reporting herbal therapy use. Seventy-three patients (96%) reported a high level of adherence (> 90%), while only 37% had a viral load < 80 copies/ml. Clinic and community-based pharmacy services were underutilized. CONCLUSIONS: Herbal therapy use was common, under-reported and difficult for providers to predict. Unreported herbal therapy use could lead to virologic failure as a result of unknown drug-herb interactions. Consultative pharmacy services in the clinic and retail pharmacies are underutilized.

Journal Article↗

Early factors in successful anti-HIV treatment.

Rapid suppression of plasma HIV RNA and sustained increase in CD4 cell count following highly active antiretroviral therapy (HAART) regimens can be prognostic indicators of long-term virologic treatment success. Routine measurement of plasma HIV RNA levels (viral load or VL) at four and eight or 12 weeks is recommended after initiating treatment because favorable changes are predictive of durable success at six months and longer. Early favorable response of VL, as soon as six days after HAART initiation, can signify that the patient is initially adherent to treatment, which is necessary in the long term for a successful regimen. Early favorable response is also an indicator of adequate pharmacokinetic profile and potent antiviral activity of the drug regimen. It also can indicate that the predominant HIV strain infecting the patient is sensitive to the treatment regimen. These factors of adherence, drug levels, potency, and susceptibility favor a long-term durable response. Evaluation of early treatment responses may create the opportunity to promptly change the HAART regimen in the event of an anticipated long-term failure, delaying or preventing the evolution of drug resistance, and improving the effectiveness of treatment overall.

Antiretroviral Therapy, Highly Active↗

Atazanavir--a once-daily HIV protease inhibitor that does not cause dyslipidemia in newly treated patients: results from two randomized clinical trials.

Protease inhibitor (PI) treatment can result in dyslipidemia in a significant proportion of patients. Atazanavir (ATV) is a once-daily PI that has not been associated with clinically relevant increases in total cholesterol (TC), fasting low-density lipoprotein cholesterol (LDL-C), or fasting triglyceride (TG) concentrations. The objectives of this paper were to evaluate lipid profiles in untreated patients, and investigate the frequency and severity of dyslipidemia in the same individuals after treatment with ATV or nelfinavir (NFV) for 48 weeks. Two multinational, randomized, active-controlled, blinded trials compared the safety and efficacy of ATV and NFV in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) in antiretroviral (ARV)-naive patients. Serum lipid concentrations were analyzed in patients who had available measurements both at baseline and at week 48. Patients who had missing data at either time point were not included. Lipid levels remained within baseline ranges at week 48 with ATV treatment, whereas clinically relevant elevations in TC, fasting LDL-C, and fasting TG concentrations occurred with NFV treatment. Mean changes from pre-treatment baseline in fasting LDL-C ranged from -6 percent to +6 percent in the ATV-treatment groups, and from +27 percent to +31 percent in the NFV-treatment groups. After 48 weeks, there was a substantive increase in the proportion of NFV-treated patients who would be recommended for lipid-lowering treatment by National Cholesterol Education Program (NCEP) guidelines, whereas a lesser proportion of ATV-treated patients would be recommended for lipid-lowering treatment. Atazanavir does not lead to dyslipidemia in ARV-naive patients, and may limit the need for lipid-lowering strategies to reduce the risk of cardiovascular disease.

Administration, Oral↗