Assessing the Benefits of Antiretroviral Therapy

• Acquired immunodeficiency syndrome
• Human immunodeficiency virus infections
• Anti-HIV agents
• Viral load
• CD4 lymphocyte count

Originally, CD4 lymphocyte count was the best available marker for assessing the prognosis of the HIV-infected patient (1). After assays to measure HIV RNA were developed, viral load was initially thought to be a better predictor of clinical progression (2). Later, in a much larger patient cohort, Mellors and coworkers (3) found that prognosis could best be predicted by looking at both viral load and CD4 cell count. Coffin (4) first used a powerful analogy to describe the different prognostic information provided by viral load and CD4 cell count: If HIV infection is a train traveling down a track and the development of AIDS is a damaged bridge ahead, the viral load is how fast the train is going and the CD4 cell count is the distance to the bridge. Pathogenetically, this makes sense: Viral load reflects the amount of viral replication occurring in an infected person, and ongoing viral replication results in CD4 cell depletion and immune compromise. In practice, viral load, CD4 cell count, and clinical status together provide important information that can be used to assess the HIV-infected patient.

Antiretroviral therapy changes the natural history of HIV infection. Early studies of one- or two-drug therapy showed modest effects on viral load and CD4 cell counts that ultimately translated to fewer clinical end points (5). With the advent of more potent drugs, notably protease inhibitors, dramatic reductions in HIV RNA level and concomitant increases in CD4 cell count have been sustained for up to 3 years of follow-up (6). At the same time, potent antiretroviral therapy has substantially improved clinical outcome both in clinical trials (7, 8) and clinical cohorts (9). Despite the success of antiretroviral therapy, however, virologic failure is common (10).

Such …