Clinical Trials of HIV-1 Reverse Transcriptase Inhibitors

• Low Two-Year Risk of Virologic Failure with First Regimen HAART (Poster 325)
  Authored by R. Levy, D. Labriola, and N. Ruiz
  View the original abstract

The issue of when to start antiretroviral therapy continues to be controversial, especially as patients enjoy the prospects of long-term survival, which needs to be balanced by concerns about long-term toxicity. Indeed, the U.S. Department of Health and Human Services released its revised guidelines at this meeting suggesting that clinicians might want to wait until total CD4 cell counts are below 350 (instead of below 500) before antiretroviral therapy is initiated. This retrospective analysis of DMP-006, an open-label randomized trial in naive patients that demonstrated that efavirenz plus AZT/3TC was more effective than indinavir plus AZT/3TC and indinavir plus efavirenz, is timely because it includes an analysis of two-year outcomes based on CD4 cell count at initiation of therapy.

The time to virologic failure (>50 copies) in the two inferior arms was longer if treatment was begun at total CD4 counts above 200; for the efavirenz-based triple therapy arm, outcome was independent of baseline CD4 cell count. For the indinavir-based triple therapy arm, the data suggest that virologic failure rates were higher if treatment was begun between 200-350 cells rather than between 350-500 cells.

The debate about when to start antiretroviral therapy is likely to rage on for the foreseeable future. While the revised US PHS guidelines indicate that the pendulum has recently swung to the more conservative side, it is important to scrutinize available data for indications that initiating therapy may be beneficial at CD4 cell counts above 350. It is crucial to remember that guidelines are just that -- guidelines -- not mandates. Initiation of therapy is a critical decision that must be individualized and arrived at by open discussion between clinician and patient. The best indicator of when to start therapy for a given patient may be when s/he is ready and committed to doing so, rather than at arbitrary CD4 cell count and viral load criteria.