Europe. A high rate of early virologic failure and emergence of nucleoside/nucleotide reverse transcriptase inhibitor resistance-associated mutations occurred in a clinical study of once-daily triple combination therapy comprising didanosine enteric coated beads (Videx), lamivudine (Epivir) and tenofovir disoproxil fumarate (Viread).
The European Agency for the Evaluation of Medicinal Products (EMEA) has issued a public statement regarding the results of this 24-week clinical study, in which virologic failure occurred in 91% of 24 HIV-infected treatment-naive patients receiving a once-daily regimen of didanosine, lamivudine and tenofovir disoproxil fumarate. The EMEA notes that the precise nature of the interactions leading to this non-response is unknown and the EMEA's Committee for Proprietary Medicinal Products has requested that the marketing authorisation holders explore these interactions. While investigations are ongoing, the EMEA advises the following precautionary measures:
• When considering a new treatment regimen, tenofovir in combination with didanosine and lamivudine should not be used, particularly as a once-daily regimen.
• Patients well controlled on this combination should be frequently monitored and considered for treatment modification if signs of virologic failure emerge.
• Patients receiving or about to receive a regimen including didanosine, lamivudine and tenofovir in combination should inform their physician immediately.
The EMEA points out that similar recommendations were made on 30 July 2003 regarding the once-daily triple therapy with abacavir, lamivudine and tenofovir. A WHO alert (WHO Drug Alert 109, available from URL http://www.who.int/medicines/library/) was also issued for the above information.
EMEA Public Statement EMEA/CPMP/5094/03, 22 October 2003. Available from URL: http://www.emea.eu.int