Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection

Abstract

The use of antiretroviral medications in HIV-negative individuals as pre-exposure prophylaxis (PrEP) is a promising approach to prevent HIV infection. Tenofovir disoproxil fumarate (TDF) and emtricitabine exhibit desirable properties for PrEP including: favourable pharmacokinetics that support infrequent dosing; few major drug-drug or drug-food interactions; an excellent clinical safety record; and pre-clinical evidence for efficacy. Several large, randomized, controlled clinical trials are evaluating the safety and efficacy of TDF and emtricitabine for this new indication. A thorough understanding of variability in drug response will help determine future investigations in the field and/or implementation into clinical care. Because tenofovir and emtricitabine are nucleos(t)ide analogues, the HIV prevention and toxicity effects depend on the triphosphate analogue formed intracellularly. This review identifies important cellular pharmacology considerations for tenofovir and emtricitabine, which include drug penetration into relevant tissues and cell types, race/ethnicity/pharmacogenetics, gender, cellular activation state and appropriate episodic or alternative dosing strategies based on pharmacokinetic principles. The current state of knowledge in these areas is summarized and the future utility of intracellular pharmacokinetics/pharmacodynamics for the PrEP field is discussed.

Short Communication: Tenofovir Diphosphate in Dried Blood Spots As an Objective Measure of Adherence in HIV-Infected Women

“…[1][2][3][4] Although drug exposure is directly related to host factors including age, weight, diet, genetics, and concomitant medications, the dominant factor impacting longterm drug exposure is adherence. [5][6][7] Unfortunately, no gold standard measure to accurately assess adherence is available in routine clinical practice.…”

Analysis of the Endogenous Deoxynucleoside Triphosphate Pool in HIV-Positive and -Negative Individuals Receiving Tenofovir-Emtricitabine

“…However, the decreased dATP and dGTP levels observed in this study do not support PNP inhibition as a dominant effect of TDF, which would theoretically induce an increase of dATP and dGTP. FTC effects may be partly explained by the inhibition of dCK, which had also been shown for another deoxycytidine analog, 3TC (8,14).…”

“…The use of TDF/FTC for PrEP, as well as long-term treatment, requires a low toxicity profile for an acceptable risk-benefit balance (14). TDF/FTC are generally safe and well tolerated (15); however, uncommon side effects have been reported, particularly in HIV-infected patients.…”

Simultaneous Method for Determination of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir and Cobicistat in Tablets By HPLC

“…The integrase inhibitor (ELV) blocks integrase enzyme while NRTIs (EMT and TDF) block reverse transcriptase enzymes of HIV. By blocking integrase and reverse transcriptase enzymes, the drugs in combination prevent HIV from multiplying and can reduce the amount of HIV in the body [1][2][3][4][5] . Hence, Stribild is a complete regimen for the treatment of HIV infection and is considered to be much more convenient method of taking these anti-HIV drugs.…”