in this issue of Cell). Nevertheless, critical aspects of AIDS pathogenesis remain to be elucidated. For example, it is still unclear how HIV-1 infection induces CD4+ T cell depletion, which is the central pathophysiologic feature of the disease. It is also uncertain how the virus persists in the presence of vigorous immune responses. Recently, important insights into these complex aspects of the host–pathogen interaction in HIV-1 infection have come from a surprisingly simple approach, the direct measurement of circulating levels of free virus. The development of rapid, sensitive, and accurate methods for quantitating virus particles in the blood has greatly facilitated the study of AIDS pathogenesis and the management of patients with HIV-1 infection. Quantitative competitive RT-PCR is carried out on blood and other biological fluids to detect genomic viral RNA, which is present at two copies per virion (