POTENTIAL APPLICATIONS OF PROVIRAL LOAD MEASUREMENT IN CLINICAL RETROVIROLOGY

We have previously noted an association between proviral load and the severity of immune disease in individuals with a wide range of CD4 cel l counts, Using the quantitative DNA polymerase chain reaction technol ogy developed in our laboratory, we sought to extend these observation s, with a view to establishing guidelines for the use of proviral load in a clinical context. We studied 199 patients with a range of CD4 ce ll counts attending an urban tertiary care center. Proviral load/10(6) peripheral blood mononuclear cells (PBMCs) was measured using a micro titer plate assay designed specifically for this purpose. Human immuno deficiency virus proviral DNA was detected in 193 of 199 clinical samp les. Levels of proviral load were tabulated for patients and evaluated in seven categories defined by CD4 cell counts. Although a wide range of proviral loads was observed in each category of patients, there wa s a trend toward increasing proviral load with decreasing CD4 cell cou nt. Statistically significant relationships were observed between prov iral load and the CD4 cell count and the CD4 cell percentage (Spearman 's correlation coefficient -0.19, p = 0.01 for both absolute CD4 and C D4 percentage). These relationships were quite weak and could not be t aken to explain disease progression in isolation. If we defined a cuto ff between low and high proviral loads at 100 copiesi/10(6) PBMCs, we noted that 52% (24 of 46) of patients with CD4 cell counts >400/mu l h ad lower loads, as compared with 16% (24 of 143) of those with more ad vanced disease (p < 0.01). There is a weak, but statistically signific ant association between proviral load and CD4 cell depletion. Although the principal clinical application of this measure will be within the context of a composite viral inventory, it may be useful as a ''thres hold'' variable, particularly following seroconversion and in early, a symptomatic disease.