COMMENTARY

Possible Causes of Early Treatment Failure With a Novel ARV Regimen

Peter J. Ruane, MB, BCh, MRCPI, Andrew D. Luber, PharmD

Disclosures

September 11, 2003

In This Article

Conclusions

In sharp contrast to clinical trial data evaluating TDF in combination with 3TC and EFV, high rates of ARV failure have been reported from studies of ARV-naive patients who received once-daily TDF in combination with ABC and 3TC as their initial therapy. Although the precise cause or causes of the early loss of antiviral potency by this regimen remain uncertain at this time, it is clear that this regimen should not be used. Moreover, until the potential factors discussed here are clarified with respect to the early treatment failures observed in recent studies, caution would seem advisable when using TDF in other triple-nucleoside regimens (eg, TDF/ABC/ddI, TDF/3TC/ddI) that include other agents that select for the K65R mutation. This approach is affirmed by the results of a recent small, prospective, open-label study of TDF/3TC/ddI in ARV-naive patients that was terminated early because of high rates of early virologic failure with similar genotypic mutational patterns (M184V with or without K65R) (Joe Jemsek, MD, personal communication).

In the case of treatment-naive patients, use of TDF/3TC combined with EFV has the most clinical experience and has shown durable treatment responses. In the absence of evidence of a negative drug interaction between TDF and ABC, it is expected that the combination of TDF plus ABC or another NRTI in a protease inhibitor-containing ARV regimen should also be effective. Coadministration with a thymidine analog, particularly zidovudine, may also be protective.[10,21] However, the efficacy of these regimens has not been studied in clinical trials, and at present cannot be recommended and should be reserved for restricted clinical situations in which other options are inappropriate.

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