Correlation between viral load measurements and outcome in clinical trials of antiviral drugs.

Background: As evidence is emerging that viral load can be correlated with clinical outcome in HIV-infected patients, new assays have been developed to measure viral load in vivo. These include biological assays that involve assessment of viral load by limiting dilution cultures of plasma or peripheral blood mononuclear cells and nucleic acid-based amplification techniques including RNA-based polymerase chain reaction and branched-chain DNA signal amplification. VIRAL LOAD QUANTITATION IN CLINICAL INVESTIGATION: The advent of RNA polymerase chain reaction and branched-chain DNA technology has allowed direct measurements of plasma HIV RNA levels. Several studies, including AIDS Clinical Trials Group (ACTG) 116B/117, the Veterans Administration Study VA CSP 298 and, more recently, ACTG 175, have indicated that viral load monitoring is a powerful predictor of disease progression and clinical outcome. A change in viral load of approximately 1 log unit is associated with an increase in CD4 cell count of about 85 cells/mm3.

Conclusions: Viral load monitoring, particularly when combined with other laboratory markers, can be correlated with clinical outcome. In routine clinical practice, viral load monitoring may be used to assess the need for changes in antiretroviral therapy, allowing individualized therapy. Viral load monitoring may also reduce the time needed for the clinical development of new therapeutic approaches, allowing earlier patient access to promising anti-HIV therapies.