Variation in the virulence of HIV-1

Viral fitness, defined as the extent of viral adaptation to the host environment, arises from tissue tropism, immune system evasion, drug resistance, and viral replication capacity. The fitness of wild type and drug resistant HIV-1 varies widely, associating with plasma viremia, CD4+ T cell count, and clinical progression. HIV-1 fitness may be measured in competitive culture assays, single cycle assays, or single cycle assays based on a sub-genomic fragment of HIV-1. The latter has been standardized as the pol replication capacity assay (pol RC). During virologic failure of anti-retroviral therapy, CD4+ T cell counts remain elevated while pol RC declines and remains durably lowered due to drug-selected changes in the pol gene. CD4+ T cell sparing is also observed among patients without evidence of drug resistance who carry a low pol RC virus. Reduced HIV-1 replication capacity and virulence may occur due to drug resistance or viral escape from host immune responses.