February 26, 2002
One of these studies, ACTG 388, was a phase III open-label randomized study of lamivudine and zidovudine given together with either indinavir (IDV), efavirenz (EFV) plus IDV, or nelfinavir (NFV) plus IDV in patients with no previous antiretroviral or limited nucleoside therapy. I think that it is fair to say that these are not regimens in common use today, and therefore, this study has very limited applicability to current clinical decision making.
There were 517 patients enrolled and they were randomized to one of the three arms of the study. The mean baseline CD4 and HIV-1 RNA were 161 cells/mm3 and 5.42 log10 copies/mL, respectively. The median time of follow-up was 2.1 years.
Of the enrolled patients, 172 experienced virologic failure. It should not be surprising, given the differences in difficulty of the various regimens, that the lowest rate of failure occurred in the EFV plus IDV arm and the highest rate of failure in the NFV plus IDV arm. In the study, 39 EFV plus IDV, 81 NFV plus IDV, and 52 IDV patients met criteria for failing therapy and when compared to the IDV alone arm, there was a lower rate of virologic failure with EFV plus IDV (p=0.04) and a higher rate with NFV plus IDV (p=0.006). The probability of achieving a viral load less than 200 copies/mL by week 24 was 87 percent with EFV plus IDV, 78 percent with NFV plus IDV, and 86 percent with IDV. Further, among the virologic responders, there was a lower rate of relapse with EFV plus IDV (p=0.009) and no significant difference between the NFV plus IDV and IDV arms. The CD4+ T cell counts increased in all groups. There was no significant difference regarding the rates of grade 3 or 4 adverse events between EFV plus IDV and IDV, but there was a trend toward an increased rate between the NFV plus IDV and IDV arms (p=0.07).
The authors of this study conclude from these data that the EFV plus IDV arm resulted in "a superior virologic response" and was relatively well tolerated, with a lower risk of toxicity than the other arms of the trial. While this may be so, I am still not convinced that this regimen is one that would be used by many clinicians, especially given the significant advances in antiretroviral therapy that have occurred in the past few years. It is a little ironic, in fact, that someone who has been so influential in establishing the importance of strict adherence to regimens would present a study in which ARV naive patients were given an extremely difficult regimen to take (IDV plus NFV), but again, it should be kept in mind that this is a study from a bygone era, one to which most of us hope never to return.
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