ORIGINAL RESEARCH The durability of virological success of tenofovir and didanosine dosed at either 400 or 250 mg once daily M-Y Tung, S Mandalia, M Bower, B Gazzard and M Nelson St. Stephens Centre, Chelsea and Westminster Hospital, London, UK Tenofovir (TDF) co-administered with didanosine (ddI) 400 mg increases ddI plasma concentrations by up to 60%, raising concerns over toxicity. To limit this interaction, the dosage of ddI may be reduced to 250 mg once daily when co-prescribed with TDF. In this clinical cohort, highly active antiretroviral therapy regimens containing TDF and ddI 250 mg were significantly better tolerated than combinations with TDF and ddI at a dose of 400 mg. Low-dose ddI 250 mg once daily plus TDF as part of antiretroviral therapy was effective. Keywords: antiretroviral therapy toxicity, drug interaction, highly active antiretroviral therapy, treatment simplification Received: 2 May 2004, accepted 25 October 2004 Introduction Highly active antiretroviral therapy (HAART) reduces the morbidity and mortality associated with HIV infection. As more potent combinations have become available to treat HIV infection, the major reasons for regimen failure have become toxicity and compliance. Tenofovir (TDF) and didanosine (ddI) are potent antiviral agents, both of which may be administered once daily. However, as ddI is hydrolysed by gastric acid, it is necessary to dose this drug in a fasting condition, which may lead to compliance issues in some individuals [1]. Clinical trials have shown that TDF when co-adminis- tered with ddI 400 mg increases ddI plasma concentration levels by up to 60% [2]. This has led to concerns over the possibility of increased toxicity and clinical side effects. Subsequent pharmacokinetic studies have demonstrated that TDF with ddI 250 mg, taken simultaneously with a light meal or in a fasting state, will give rise to plasma levels of ddI equivalent to those achieved when ddI is dosed as 400 mg alone [3]. However, the effect on intracellular triphosphate levels is unknown. There have been recent concerns regarding CD4 count toxicity with the use of TDF when combined with standard dose ddI 400 mg, with a study demonstrating an adverse effect on CD4 cell count when this combination was used [4]. The objective of this study was to assess the clinical tolerability and effectiveness of HAART combinations containing TDF and ddI 250 or 400 mg. Methods Details of all HIV antibody-positive individuals are held on a departmental computerized database. A retrospective analysis was undertaken of all individuals documented to have received TDF in combination with ddI as part of a HAART regimen. To ascertain full case retrieval, this database was cross-checked with a separate database in the pharmacy department of our unit. All patients were virologically controlled, with a viral load of less than 50 HIV-1 RNA copies/mL at entry on at least two separate occasions 1 month apart. Individuals who switched regi- mens because of toxicity or who experienced virological failure were censored at this time. Seventy-eight individuals who had a viral load of o50 copies/mL, and who were receiving an antiretroviral regimen containing TDF and ddI at either 250 or 400 mg, were identified. Of these individuals, 33 were receiving TDF in combination with ddI 250 mg once daily and 45 were receiving TDF with ddI 400 mg once daily. Individuals receiving ddI 250 mg with TDF were instructed to take their medication simultaneously with a light meal or in a fasting state. Individuals receiving ddI 400 mg were instructed to take the ddI separately from the TDF, at least 2 h apart and in a fasting state. Individuals receiving ddI 400 mg were part of a historical cohort, treated prior to the interaction between TDF and ddI being described. Individuals receiv- ing ddI 250 mg all started their new combination from July Correspondence: Dr Mun-Yee Tung, St. Stephens Centre, Chelsea & Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK. Tel: 1 44 208746 8000; fax: 1 44 208726 5611; e-mail: Mun-Yee.Tung@chelwest.nhs.uk r 2005 British HIV Association HIV Medicine (2005), 6, 151–154 151