Closing the Door to Human Immunodeficiency Virus.

Closing the door to human immunodeficiency virus.

Protein Cell. 2013 Feb; 4(2): 86-102
Kang Y, Guo J, Chen Z

The pandemic of human immunodeficiency virus type one (HIV-1), the major etiologic agent of acquired immunodeficiency disease (AIDS), has led to over 33 million people living with the virus, among which 18 million are women and children. Until now, there is neither an effective vaccine nor a therapeutic cure despite over 30 years of efforts. Although the Thai RV144 vaccine trial has demonstrated an efficacy of 31.2%, an effective vaccine will likely rely on a breakthrough discovery of immunogens to elicit broadly reactive neutralizing antibodies, which may take years to achieve. Therefore, there is an urgency of exploring other prophylactic strategies. Recently, antiretroviral treatment as prevention is an exciting area of progress in HIV-1 research. Although effective, the implementation of such strategy faces great financial, political and social challenges in heavily affected regions such as developing countries where drug resistant viruses have already been found with growing incidence. Activating latently infected cells for therapeutic cure is another area of challenge. Since it is greatly difficult to eradicate HIV-1 after the establishment of viral latency, it is necessary to investigate strategies that may close the door to HIV-1. Here, we review studies on non-vaccine strategies in targeting viral entry, which may have critical implications for HIV-1 prevention. HubMed – drug


Dyslipidemia in Type 2 Diabetes: Prevalence, Pathophysiology, and Management.

Drugs. 2013 Mar 12;
Chehade JM, Gladysz M, Mooradian AD

Dyslipidemia is one of the key risk factors for cardiovascular disease (CVD) in diabetes mellitus. Despite the mounting clinical trial data, the management of dyslipidemia other than lowering the low density lipoprotein cholesterol (LDL-c) continues to be controversial. The characteristic features of diabetic dyslipidemia are high plasma triglyceride concentration, reduced high density lipoprotein cholesterol (HDL-c) concentration, and increased concentration of small dense LDL particles. These changes are caused by increased free fatty acid flux secondary to insulin resistance and aggravated by increased inflammatory adipokines. The availability of several lipid-lowering drugs and nutritional supplements offers novel and effective options for achieving target lipid levels in people with diabetes. While initiation of drug therapy based on differences in the lipid profile is an option, most practice guidelines recommend statins as first-line therapy. Although the evidence for clinical utility of combination of statins with fibrates or nicotinic acid in reducing cardiovascular events remains inconclusive, the preponderance of evidence suggests that a subgroup who have high triglycerides and low HDL-c levels may benefit from combination therapy of statins and fibrates. The goal of therapy is to achieve at least 30-40 % reduction in LDL-c levels. Preferably the LDL-c should be less than 100 mg/dL in low-risk people and less than 70 mg/dL in those at high risk, including people with established CVD. HubMed – drug


A Review of the Pharmacokinetic Implications of Schistosomiasis.

Clin Pharmacokinet. 2013 Mar 12;
Wilby KJ, Gilchrist SE, Ensom MH

Schistosomiasis is a common parasitic disease, with over 230 million people requiring treatment annually. The worldwide increase in medication access poses risks for patients living in regions endemic for schistosomiasis because of the potential impact of pharmacokinetic changes on clinical outcomes. Thus, the objective of this review is to summarize and evaluate the published literature reporting pharmacokinetic parameters of medications in patients with schistosomiasis and to assess associated clinical implications. Thirteen articles that described the pharmacokinetics of a total of 9 different medications (cefoperazone, propranolol, praziquantel, theophylline, metronidazole, acetaminophen/paracetamol, antipyrine, oxamniquine, and oral contraceptives) in patients with schistosomiasis were included in the review. The major finding is that pharmacokinetic changes occur in patients infected with schistosomiasis but to varying degrees depending on the extent of disease (e.g., varying stages of fibrosis, with or without signs and/or symptoms of liver disease) and medication being administered. Affected patients may consequently be at risk of adverse clinical outcomes. In general, drugs with high extraction ratios demonstrate increased bioavailability in patients with schistosomiasis compared to controls. For example, propranolol and praziquantel, respectively, show an association with increased clinical and toxic effects in patients with schistosomiasis. Conversely, the pharmacokinetics of low hepatic clearance drugs (such as metronidazole and oxamniquine) are largely unchanged unless patients present with liver disease (as in the case of antipyrine, the prototypical low clearance drug). Limitations of studies included the very small numbers of patients, being primarily single-dose studies, and the high inter-individual variability. Future clinical studies should include pharmacokinetic outcomes to further clarify dosing and administration strategies for target medications, especially those that primarily undergo metabolism and are associated with significant adverse effects. Until the results of these future studies are available, clinicians should be acutely aware of complications from schistosomiasis and carefully screen patients for signs and symptoms of liver disease prior to prescribing, dispensing, or administering potentially harmful medications. HubMed – drug