Truvada from Gilead is a new drug just approved for HIV.
According to the Joint United Nations Program on HIV/AIDS, an estimated 1.2 million adults and children were living with this condition in the United States at the end of 2003, with an estimated 40,000 new HIV infections occurring in the same year.
Four different classes of antiretro-viral agents exist for treating HIV/ AIDS: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and fusion inhibitors. The Food & Drug Administration has now approved a new agentemtricitabine/ tenofovir disoproxil (Truvada, Gilead Sciences).
The two components in the new fixed-dose combination product are already on the market, said Frank Romanelli, Pharm.D., BCPS, associate professor at college of pharmacy and college of health sciences at the University of Kentucky. Emtriva (emtricitabine 200 mg) and Viread (tenofovir disoproxil 300 mg) are two of Gilead's reverse transcriptase inhibitors.
HIV/AIDS patients use three or more different drugs once, twice, or three times a day. Improving patient adherence to antiretroviral therapy, so important for managing HIV/AIDS, has been a critical initiative for many pharmaceutical companies, said Romanelli. He believes Truvada's once-daily dosing will provide a significant advantage by reducing pill burden. The cost of Truvada is comparable to that of purchasing the products individually, he added.
Jim Scott, Pharm.D., assistant professor of pharmacy practice at Western University of Health Sciences, noted that effectiveness, tolerability, and favorable pill burden are some positive aspects of Truvada. Epzicom (abacavir sulfate/lamivudine, GlaxoSmithKline), Combivir (lamivudine/zidovudine, GSK), or Truvada will be part of the nucleoside backbone in highly active antiretroviral therapy (HAART) for patients beginning therapy, said Scott. Efficacy data support all three products, he said, but head-to-head studies are needed.
Truvada can be used in combination with other antiretroviral agents (such as NNRTIs or PIs) for treating HIV-1 infection in adults. It has not been studied in children under age 18 or adults over 65. The recommended dosage is one tablet (200 mg of emtricitabine/300 mg of tenofovir disoproxil) once a day orally with or without food. The dosing interval of Truvada should be adjusted to one tablet every 48 hours in patients with baseline creatinine clearance 30-49 mL/min. Gilead Sciences does not recommend the use of Truvada in patients with a creatinine clearance < 30 ml/min, in patients requiring hemodialysis, or in those with concurrent or recent use of nephrotoxic agents. The company plans to include Truvada in its Gilead Access Program to increase access to antiretroviral medications in developing countries at nonprofit pricing.
Safety and efficacy studies using Truvada tablets or using emtricitabine and tenofovir disoproxil in combination are ongoing. Since emtricitabine and lamivudine (3TC) have similar structures, resistance profiles, and safety/efficacy as components in multi-drug regimens, existing data from the use of lamivudine and tenofovir disoproxil have been extrapolated to support the use of Truvada. The new drug will have the same side effectsamong them nausea, vomiting, diarrhea, and headachesas the individual products. In clinical trials, additional adverse events occurred in >5% of patients receiving emtricitabine, including asthenia, dizziness, rash, and skin discoloration. Rash and depression occurred in > 5% of patients receiving tenofovir disoproxil.
Renal impairment and decreases in bone mineral density at the lumbar spine and hip have been reported. A Black Box warning reports that lactic acidosis and severe hepatomegaly with steatosis have occurred with the use of nucleoside analogs alone or in combination with other antiretrovirals. Truvada is not indicated for treating chronic hepatitis B virus infection.