HIV RNA is an acknowledged marker of disease activity and predictive of progression, while the p24 antigen is considered unsuitable. This is at odds with the fact that viral pathogenesis is usually mediated by proteins. One might expect that p24, if analyzed properly, might even be superior to RNA. This hypothesis was investigated in clinical studies using a sensitive and precise p24 test (heat-mediated immune complex dissociation with signal amplification-boosted ELISA). This test was as sensitive and specific as the polymerase chain reaction (PCR) for viral RNA (200-400 copy detection), an overall better predictor of CD4 decline and survival, while RNA prevailed in predicting AIDS. The lower costs of p24 testing also permit a closer monitoring of patients with an earlier detection of anti-retroviral treatment failures.