HIV-1 isolates with reduced susceptibility to the combination of emtricitabine and tenofovir have been selected in vitro. Genotypic analysis of these isolates identified the M184V/I and/or K65R amino acid substitutions in the viral reverse transcriptase.
Cross-resistance among certain NRTIs
has been recognized. The M184V/I and/or K65R substitutions selected in vitro by the combination of emtricitabine and tenofovir are also observed in some HIV-1 isolates from subjects not responding to treatment with tenofovir in combination with either or emtricitabine with either the NRTI aba-cavir sulfate (Ziagen®, GlaxoSmith-Kline) or the NRTI didanosine (ddl, Videx®, Bristol-Myers Squibb Immu-nology). Therefore, cross-resistance among these drugs may occur in patients whose virus harbors either or both of these amino acid substitutions.
ADVERSE DRUG EFFECTS
Safety and efficacy studies of Truvada™ tablets (Emtriva®/Viread®) are ongoing. Two hundred eighty-three HIV-1 infected patients have received combination therapy with Emtriva® or Viread® with either an NNRTI or a PI for 24 to 48 weeks in ongoing clinical studies. According to these limited data, no new patterns of ADEs were identified. There was no increased frequency of established toxicities.
ADEs associated with emtricitabine in more than 5% of patients include abdominal pain, asthenia, headache, diarrhea, nausea, vomiting, dizziness, and rash. ADEs associated with tenofovir in more than 5% of patients include headache, nausea, vomiting, diarrhea, rash, and depression. Truvada™ therapy can result in severe lactic acidosis, osteopenia, elevated serum cholesterol and triglyceride levels, lipodystrophy, and diabetes. canadian pharmacy viagra
Truvada™ is contraindicated in those patients with a hypersensitivity to any of the components of the product. It is a pregnancy category B drug.
Administering Truvada™ with the NRTI didanosine (ddl) should be undertaken with caution. Patients receiving this combination should be monitored closely for didanosine-associated ADEs, including pancreatitis and neuropathy. Patients receiving the PIs atazanavir (Reyataz®, Bristol-Myers Squibb Virology) and lopinavir/ritonavir (Kaletra®, Abbott) and Truvada™ should be monitored for any associated ADEs because of the resulting elevated tenofovir concentrations with these combinations.
Truvada™ should be discontinued if associated ADEs occur. Atazanavir without the PI ritonavir (Abbott) should not be administered with Truvada™.
Because emtricitabine and tenofovir are eliminated primarily by the kidneys, taking Truvada™ with drugs that reduce renal function or that compete for active tubular secretion may increase serum concentrations of emtricitabine, teno-fovir, or other renally eliminated drugs. Examples include, but are not limited to, adefovir dipivoxil (Hepsera®, Gilead), cidofivir injection (Vistide®, Gilead), canadian acyclovir (Biovail), (Valtrex canadian, GlaxoSmithKline), ganciclovir (Cytovene®, Roche), and val-ganciclovir (Valcyte®, Roche).
Truvada™ should not be taken with Emtriva® or Viread® when either is used alone. Because of the similarities between emtricitabine and lamivudine, patients should not take Truvada™ with other drugs containing such as (lamivudine), Epivir® (lamivudine), ® (lamivudine), Epzicom® (Epivir canadian/ Ziagen®), or Trizivir® ( lamivudine/zidovudine). Truvada™ should not be used as a component of a triple-nucleoside regimen.
DOSAGE AND ADMINISTRATION
Truvada™ is given as one tablet containing 200 mg of emtricitabine and 300 mg of tenofovir. It can be taken orally with or without food once a day. Each tablet is film-coated for oral administration.
The use of highly active antiretroviral therapy (HAART) has been associated with decreased morbidity and mortality. HAART is indicated to prevent immune deterioration leading to immunodeficiency (a CD4 count below 200 cells/ mm3). Because of the pill count burden and the frequency of administration, adherence to HAART therapy has been low. New combination medications such as Truvada™ offer alternatives that should increase patient compliance. This drug prevents HIV from altering the genetic material of healthy T cells, thus preventing the cells from producing new viral cells and reducing the amount of the virus in the body.
Truvada™ should be considered for patients who are treatment-naive or who might benefit from a once-daily regi-men. No results have yet demonstrated the effect of this agent on the clinical progression of HIV-1, and no drug-drug interaction studies of Truvada™ tablets have been conducted.