Use of Surrogate Versus Clinical Markers in Trials for HIV Infection

In an era of proliferating antiretroviral therapies, clinical endpoint trials have become problematic in terms of their lengthy durations, excessive sample sizes, and resource requirements. Rapid developments in the HIV field can also impact an ongoing clinical endpoint trial, resulting in changes to the treatment arms, accrual problems, and pressure to terminate the study prematurely. Thus, there are increasing arguments for the use of surrogate markers in preference to clinical endpoints. Plasma HIV-1 RNA is pathogenetically plausible as a surrogate marker, and is currently the strongest predictor of clinical outcome. It is also easily measurable and responsive to active agents. A combination of viral load measurements such as proportion of subjects below the limit of detection and change from baseline should be utilized to provide a more immediate assessment of disease status. Also, plasma HIV-1 RNA is best used in combination with other markers, such as the CD4 cell count, that carry prognostic significance.