In summary, much still needs to be learned about the pathogenetic significance of changes in virus load and importantly, the clinical significance of therapy-induced changes in virus load. The failure of current therapeutic regimens to effect a substantive and durable change in virus load is not a failure of the virologic markers per se but is a call for better antiretroviral and immunotherapeutic-based approaches to treat infected patients. At the same time, the experimental therapeutic regimens should be used to elucidate the unresolved pathogenetic nuances of HIV-1 burden that are a necessary prerequisite for developing a more effective containment of replicating HIV-1 and prolonging the lives of our HIV-1-infected patients.