February 9, 2004
Treating HIV-infected patients over the years has taught us that the potency of an antiretroviral regimen is a very important predictor of treatment success. But there are other factors that can influence our patients' treatment response. As we develop new drugs, novel combinations and simplified treatment strategies, it is important that we pay close attention to factors associated with virologic success and virologic failure. The identification of those factors is essential in order to maximize treatment response. With this goal in mind, investigators with the old ACTG 388 study attempted to identify the factors which affected treatment response in patients who had participated in this trial.
ACTG 388 was a randomized phase III clinical trial of mainly antiretroviral-naive subjects with advanced HIV disease. In it, patients were randomized to receive zidovudine (ZDV, Retrovir) and lamivudine (3TC, Epivir) in combination with indinavir (IDV, Crixivan), indinavir/efavirenz (EFV, Sustiva) or indinavir/nelfinavir (NFV, Viracept). The results of this study, published several years ago, showed that the combination of zidovudine/lamivudine plus indinavir/efavirenz offered a superior virological response to the combination of zidovudine/lamivudine plus indinavir. Zidovudine/lamivudine plus indinavir/nelfinavir resulted in an inferior virologic response. In that initial study report, a subgroup of patients was identified as having an increased risk of virologic failure; this group included patients who had poor adherence, were female and were younger.
In the poster presented at this conference, Dr. Ribaudo and colleagues analyzed baseline and on-treatment factors associated with virologic failure in the 517 initial ACTG 388 patients, who were followed for up to 108 weeks. A multivariate analysis was then conducted on the 172 patients who experienced virologic failure. This analysis revealed that the following factors increased the risk for virologic failure:
What is the importance of this study in today's practice? Although the drug combinations used in this study are not commonly used in practice today, it is possible that some of the factors identified in this analysis may still explain the virologic failure that we currently observe in some of our patients. After all, even with the simplified treatment combinations used today, poor virologic response is still observed in approximately 10% of the treatment-naive population.
By understanding the factors associated with an increased risk for virologic failure, we can improve the outcome for those subjects. We could potentially develop strategies to help, for example, younger patients as well as non-white and female patients. These data also reinforce the concept that interruption of treatment can increase the risk of virologic failure. On the other hand, these data again support what has been presented in many other studies regarding the presence of intermittent viral load blips, and the assertion that intermittent viremia may not be a big deal.
Abstract: Factors Associated With Virologic Failure and Their Impact on Treatment Outcomes: An Analysis of Virologic Failure in ACTG 388 (Poster 553)
Authored by: H. Ribaudo, G. Downey, M. Fischl, J. Feinberg, A. Erice, A. Collier
Affiliations: Harvard Sch. of Publ. Hlth., Boston, MA; Univ. of Miami, FL; Univ. of Cincinnati, OH; Hosp. Asepeyo, Madrid, Spain; Univ. of Washington, Seattle, WA
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