SURROGATE MARKERS IN HIV DISEASE

The use of surrogate markers in HIV disease is an attractive method of assessing the efficacy of new treatments more quickly than by using c linical end-points. The characteristics of an ideal surrogate marker a nd the theoretical dangers of extrapolating properties from one class of drug to another are described. These characteristics are compared w ith the use of the CD4 lymphocyte count, which so far has been the mos t widely studied. Results from 14 randomized controlled trials of nucl eoside analogues are used to compare the comparative changes of CD4 co unts with the differential rates of progression to AIDS and difference s in survival. There was some correlation between CD4 count changes an d development of AIDS, particularly in the short term trials. In contr ast, there was little correlation between CD4 counts and overall survi val. Comparative studies between clinical end-points and quantitative measures of plasma viraemia have not yet been completed. In conclusion , no surrogate marker has yet been shown to be useful in predicting th e efficacy of anti-HIV treatment. Until surrogate markers are validate d against the results from long term clinical trials, they should only be used to screen new drugs warranting further study rather than to d raw conclusions on the clinical efficacy of new treatments.