Tenofovir disoproxil fumarate.
OBJECTIVE
To review the pharmacology, virology, pharmacokinetics, efficacy, safety, resistance profile, and clinical use of tenofovir disoproxil fumarate.


METHODS
A MEDLINE search was performed (1966-August 2002) using the following terms: tenofovir, tenofovir disoproxil fumarate, PMPA (9-(R)-[2-(phosphonomethoxy)propyl]adenine), and Viread. Abstracts from HIV-related meetings were reviewed. DATA EXTRACTION AND STUDY SELECTION: Publications and meeting abstracts regarding tenofovir were reviewed. The most recent and pertinent items were included.


RESULTS
Tenofovir disoproxil fumarate is a nucleotide prodrug that is diphosphorylated to its active moiety, tenofovir diphosphate. In this form, tenofovir acts as a reverse transcriptase inhibitor to inhibit HIV-1 replication. In clinical trials, tenofovir was effective at suppressing HIV-1 RNA and boosting CD4+ cell counts. Tenofovir has a long intracellular half-life, which permits once-daily dosing. Since tenofovir does not interact with the cytochrome P450 pathway, it exhibits minimal drug interactions, with the exception of didanosine. Compared with other reverse transcriptase inhibitors, tenofovir may have advantages in terms of toxicity and medication adherence profiles. Ongoing studies are also analyzing tenofovir's activity against hepatitis B virus.


CONCLUSIONS
Tenofovir has been shown to be active against HIV-1 in combination with other antiretrovirals. The drug's benefit as a single-agent intensifier of highly active antiretroviral therapy in treatment-experienced patients has been established, and preliminary data for treatment-naïve patients are encouraging.
Grim
Shellee A
SA
University of Kentucky, Lexington, KY 40536-0293, USA. sgrim2@uky.edu
Romanelli
Frank
F
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000068698:Tenofovir
D063065:Organophosphonates; D009943:Organophosphorus Compounds; D000068698:Tenofovir; D000225:Adenine