The level of plasma HIV RNA is proportional to the rate of viral replication and the rate of CD4 lymphocyte destruction. In this study, the viral load had a higher prognostic value than the CD4 lymphocyte count. As the Figure illustrates, the natural history of HIV infection varies from individual to individual, and the plasma HIV RNA level can help predict the rapidity with which clinical immunodeficiency develops. Numerous studies have shown that the effects of antiretroviral therapy on these two markers strongly predict the likelihood of disease progression, including death. These studies also demonstrate that greater reductions in viral load are associated with greater improvements in clinical outcome.
Viral replication leads to the generation of viral mutants.
Some of these mutants will be resistant to one or more antiretroviral drugs. Incomplete inhibition of viral replication leads to the emergence of drug-resistant populations and to resumption of disease progression. 10,11 Emergence of drug resistance can be delayed or prevented by maximal suppression of viral replication. 12 Complete immune reconstitution, particularly for those who have advanced HIV disease, may not be possible. In other words, the loss of CD4 lymphocyte clones as the disease progresses may not be entirely reversible.