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Chapter: Modern Pharmacology with Clinical Applications: Therapy of Human Immunodeficiency Virus

Drug Therapy of HIV Infection: Nucleotide Reverse Transcriptase Inhibitors

Tenofovir disoproxil fumarate (Viread) is a prodrug of tenofovir, a phosphorylated adenosine nucleoside ana-logue, and is the only available agent of its class .

Nucleotide Reverse Transcriptase Inhibitors

Tenofovir

 

Tenofovir disoproxil fumarate (Viread) is a prodrug of tenofovir, a phosphorylated adenosine nucleoside ana-logue, and is the only available agent of its class . It is converted by cellular enzymes to tenofovir diphos-phate, which competes with deoxyadenosine triphos-phate (dATP) for access to reverse transcriptase and causes chain termination following its incorporation. Tenofovir was approved as part of a combination ther-apy for HIV in adults who failed treatment with other regimens; it appears to be effective against HIV strains that are resistant to NRTIs. The pharmacokinetic prop-erties of tenofovir are provided in Table 51.2.


 

Tenofovir is taken once daily and is generally well tolerated, perhaps because it produces less mitochondr-ial toxicity than the NRTIs. Nausea, vomiting, flatu-lence, and diarrhea occur in 10% or fewer patients. Resistance to tenofovir has been documented, and cross-resistance to NRTIs may occur.

 

Tenofovir should not be given to patients with renal insufficiency. Its coadministration with didanosine re-sults in increased plasma levels of didanosine that can produce toxicity. Because lactic acidosis and severe he-patomegaly with steatosis have been reported with NRTIs, it is important to monitor patients with known risk factors during treatment with tenofovir.

 

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Modern Pharmacology with Clinical Applications: Therapy of Human Immunodeficiency Virus : Drug Therapy of HIV Infection: Nucleotide Reverse Transcriptase Inhibitors |


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