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High virological failure rate in HIV patients after switching to a regimen with two nucleoside reverse transcriptase inhibitors plus tenofovir

Pérez-Elías, Maria Jesús; Moreno, Santiago; Gutiérrez, Carolina; López, Dolores; Abraira, Victor; Moreno, Ana; Dronda, Fernando; Casado, Jóse Luis; Antela, Antonio; Rodríguez, Miguel Angel

doi: 10.1097/01.aids.0000166092.39317.42
Clinical Science: Concise Communication

Background: Regimens with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus tenofovir DF have been associated with a high failure rate when administered as first line therapy. Little is known about patients with undetectable viral loads who are switched to these regimens.

Methods: A post-hoc review of the virological outcomes at 24 weeks of patients who switched from a successful (< 50 copies/ml) highly active antiretroviral therapy regimen to a tenofovir plus two NRTI combination.

Results: Fifty-five patients started a two NRTI plus tenofovir regimen mostly because of previous toxicity/intolerance of the original drugs (74%). After 24 weeks, only 17 patients (31%) remained virologically suppressed. Patients with a regimen including a didanosine plus tenofovir-based regimen had significantly poorer outcomes than those on other combinations (success rate 5 versus 47.1%, P = 0.001). In contrast, patients on a regimen including zidovudine plus tenofovir showed a trend towards a better outcome (75 versus 27%, P = 0.083). Multivariate analysis confirmed the combination of didanosine plus tenofovir as the only variable associated with a higher rate of failure (odds ratio 17.7; 95% confidence interval 2.1–147; P = 0.007). Patients with previous reverse transcriptase mutations presented virological failure in all cases. At failure a new pattern, including the K65R mutation with M184V or thymidine analogue mutations, was observed.

Conclusions: Even in patients with suppressed viraemia, a two NRTI plus tenofovir regimen is associated with a high virological failure rate, but significant variations are found depending on the nucleosides included.

Infectious Diseases Unit, Hospital Ramón y Cajal, Madrid, Spain.

Received 29 June, 2004

Revised 6 December, 2004

Accepted 22 December, 2004

Correspondence to Maria Jesús Pérez-Elías, Infectious Diseases Unit, Ramón y Cajal Hospital, Madrid 28034, Spain. Tel: +34 91 3368672; fax: +34 91 3368672; e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.