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Recent developments in the clinical pharmacology of anti-HIV nucleoside analogs

Purpose of review This review summarizes recent developments regarding the unique clinical pharmacologic profile of nucleoside analog reverse transcriptase inhibitors for management of HIV. Recent findings First, intracellular data in patients suggest that nucleoside reverse transcriptase inhibitor-triphosphates are compartmentalized in different cell types. Additionally, intracellular drug–drug interactions were identified, which were undetectable in plasma. Second, extracellular data illustrate multiple bidirectional plasma drug–drug interactions between renally eliminated tenofovir and liver-metabolized drugs. Definitive mechanistic details for these interactions are lacking but they appear to involve renal and/or enteric drug transporters. Furthermore, the plasma versus female genital tract disposition of these agents was recently elucidated, which is important for currently investigated indications for pre-exposure and post-exposure prophylaxis. Finally, tenofovir/emtricitabine and abacavir (using a promising human leukocyte antigen-B*5701 genetic test for hypersensitivity)/lamivudine have emerged as common first-line nucleoside analog reverse transcriptase inhibitors because of co-formulations, once-daily dosing, and favorable tolerability and adverse effect profiles. Nevertheless, elucidating the long-term safety profile for all nucleoside analog reverse transcriptase inhibitors remains a priority. Summary Knowledge of nucleoside analog reverse transcriptase inhibitor disposition intracellularly and extracellularly has expanded. This provides a basis for rational use of these agents clinically and adds new perspectives for future research.