Pharmacokinetics of Ruxolitinib in HIV Suppressed Individuals on Antiretroviral Agent Therapy from the ACTG A5336 Study.

Ruxolitinib is a US Food and Drug Administration-approved orally administered Janus kinase (1/2) inhibitor that reduces cytokine-induced inflammation. As part of a randomized, phase 2, open-label trial, ruxolitinib (10 mg twice daily) was administered to HIV-positive, virologically suppressed individuals (33 men, 7 women) on antiretroviral therapy (ART) for 5 weeks. Herein, we report the population PK subsequently determined from this study.

Compatibility of next-generation first-line antiretrovirals with rifampicin-based antituberculosis therapy in resource limited settings.

Purpose Of Review: Reduced dose efavirenz, dolutegravir, and/or tenofovir alafenamide (TAF) are likely to be used in the next generation of first-line antiretroviral therapy in resource limited settings, where HIV-associated tuberculosis is common. Rifampicin, which is a key component of first-line antituberculosis therapy, is a potent inducer of many drug transporters and metabolising enzymes. We reviewed the literature for potential or actual drug--drug interactions between these antiretrovirals and rifampicin.

Universal antiretroviral regimens: thinking beyond one-pill-once-a-day.

Purpose Of Review: Poor adherence to oral antiretroviral treatment in a subpopulation of persons with HIV-1 infection interferes with the potential success of the drug regimens in treating the infection. Here, we review long-acting antiretroviral strategies currently in clinical development that could prove useful for the treatment of HIV-1 infection in individuals not succeeding with short-acting oral regimens.

Recent Findings: Pharmaceutical nanotechnology has succeeded in creating two novel long-acting injectable antiretroviral compounds, carbotegravir and rilpivirine, which have completed early clinical trials demonstrating the safety, tolerability and prolonged antiretroviral activity.

Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today.

Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir.

Background: Complementary and alternative medicine (CAM) use is prevalent among HIV-infected patients to reduce the toxicity of antiretroviral therapy. Ginseng has been used for treatment of hyperglycemia and insulin resistance, a common side effect of some HIV-1 protease inhibitors (PI). However, it is unknown whether American ginseng (AG) can reverse insulin resistance induced by the PI indinavir (IDV), and whether these two agents interact pharmacologically.

The pharmacology of antiretroviral nucleoside and nucleotide reverse transcriptase inhibitors: implications for once-daily dosing.

The trend toward once-daily dosing in HIV antiretroviral therapy is based on the association between adherence, treatment outcome, and patient preferences. Patients prefer simpler treatments, fewer pills, less frequent dosing, and no food restrictions. When a regimen meets a patient's preferences, the patient is more likely to be adherent, and with good adherence, the regimen is more likely to be effective.

Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection.

AMD3100 is a CXCR4 receptor inhibitor with anti-HIV-1 activity in vitro. We tested the safety, pharmacokinetics, and antiviral effect of AMD3100 administered for 10 days by continuous intravenous infusion in an open-label dose escalation study from 2.5 to 160 microg/kg/h.

Advances in HIV pharmacology: protein binding, pharmacogenomics, and therapeutic drug monitoring.

Developing better antiretroviral drugs, individualizing therapy through patient genetic profiling, and maintaining effective drug concentrations with therapeutic drug monitoring (TDM) represent 3 current areas of interest in the field of HIV pharmacology. This article first examines antiretroviral drug binding to plasma proteins, a factor that affects the amount of free drug available to enter cells. Protein binding influences drug development, raising questions about whether the drug levels required for appropriate therapeutic effect can be achieved at tolerable doses.

Directly administered antiretroviral therapy in the treatment of HIV infection: benefit or burden?

While combination antiretroviral treatment has had a profound impact on the morbidity and mortality of human immunodeficiency virus (HIV) infection, the adherence demands of this therapy are high and failure to maintain viral suppression is common. Directly administered antiretroviral therapy (DAART) has garnered attention recently as a strategy to improve medication adherence and clinical outcomes in HIV-infected individuals. This review is intended to provide an update on the use of DAART and the challenges posed by this strategy, explore settings in which DAART may be used, discuss the role of antiretroviral regimens with improved pharmacokinetic features, and propose future directions for DAART strategies.

Alcohol use and HIV pharmacotherapy.

Alcohol consumption by individuals infected with HIV is an important medical management issue with significant implications for the effectiveness of antiretroviral therapy as well as an important evolving field of HIV research. Alcohol consumption is a risk factor for poor medication adherence and can modify liver drug metabolism, both of which can lead to the emergence of drug-resistant virus. Research indicates that alcohol consumption greater than 50 g/day (four or five drinks) is a risk factor for liver disease progression among patients with HIV/HCV coinfection.