Prospective longitudinal analysis of viral load and surrogate markers in relation to clinical progression in HIV type...

The temporal relationship between viral and surrogate markers and clinical status was analyzed prospectively every 8 weeks in 34 asymptomatic HIV-1-infected persons. After 3 years, 25 persons remained clinically healthy whereas 9 persons showed clinical progression. In accordance with other reports we found that at study entry HIV-RNA load was predictive of clinical progression. All markers tested evolved significantly in time in both progressors and nonprogressors. The HIV RNA load in plasma and HIV DNA load in T cells were linearly related only in nonprogressors. In addition, the RNA/DNA ratio during follow-up was significantly higher in progressors, indicating a higher replication rate in progressors. The HIV DNA load correlated inversely with CD4+ T cell counts and positively with p24 antigenemia in both nonprogressors and progressors. A significant correlation of HIV DNA load with SI phenotype occurred in progressors only. HIV RNA levels correlated with beta 2-microglobulin level and with p24 antigenemia but not with SI phenotype. These three markers can all routinely be measured in plasma; however, only the HIV RNA levels appear to be informative for clinical progression. Six to 8 months before clinical progression, an SI phenotype switch, increased HIV RNA in plasma, and decreased CD4+ T cell counts were all indicative of an impending clinical event.