HIV-1 Fitness and Replication Capacity: What Are They and Can They Help in Patient Management?

The natural history of HIV-1 infection is characterized by persistent viremia, progressive CD4 lymphopenia, and profound immune suppression resulting in opportunistic infections, neoplasms, and death. Introduction of combination antiretroviral therapy has been effective in suppressing HIV-1 replication, reversing immunodeficiency to a degree, reducing HIV-1-associated complications, and thereby prolonging life. One of the most vexing challenges of prolonged antiretroviral therapy is the development of drug resistance. Antiretroviral therapies fail in a substantial number of cases, often with emergence of HIV-1 variants encoding mutations that confer potent drug resistance to individual agents or entire drug classes. Resistance testing methods have been introduced to evaluate drug resistance, and several studies have reported clinical benefits of genotyping and phenotyping assays in clinical decision-making. However, the genetic variability of HIV-1 to develop resistance exceeds the antiretroviral armamentarium, and the number of patients with drug experience and resistance to all classes of antiretrovirals continues to grow. From a clinical standpoint, it would be useful to have a more comprehensive grasp of pathogenic determinants of HIV-1 in all patients. One proposed in vitro correlate of HIV-1 pathogenic potential is the replication capacity of HIV-1. New techniques to assess HIV-1 replication potential are in development, with a commercial assay now available to analyze clinical samples. In this review we explore the experimental basis for replication capacity measurements and potential clinical applications of this methodology.