Prospective longitudinal analysis of viral load and surrogate markers in relation to clinical progression in HIV type 1-infected persons

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,vith SI phenotype occurred in progressors only, HIV RNA levels correlated,vith 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.