MEASURING VIRAL LOAD IN THE CLINICAL SETTING

The traditional approach of assessing new treatments in clinical end-p oint studies is becoming less viable for ethical and practical reasons . As more antiretroviral options become available and as treatment is commenced at earlier, asymptomatic stages of infection, alternative me thods of assessing the efficacy of antiretroviral regimens are necessa ry. Recently developed quantitative measures of viral nucleic acids ar e already proving invaluable in predicting which drugs and combination s are most promising for further investigation. These approaches have been used to evaluate the effect of antiretroviral drugs in clinical t rials comparing zidovudine (AZT) monotherapy with combinations of AZT/ didanosine (ddI), AZT/zalcitabine (ddC), and AZT/lamivudine (3TC). In one study (Trial BW 34,225-02), levels of HIV-1 RNA in serum fell by a pproximately 50% in antiretroviral-naive patients on commencement of A ZT monotherapy. For patients treated with AZT/ddI and AZT/ddC, reducti ons in serum HIV-1 RNA levels were significantly greater (80-90%). Inc reases in CD4 cell count corresponded with these decreases in viral lo ad. A second study (Trial NUCB3001) comparing the effect of AZT monoth erapy with AZT/3TC therapy in antiretroviral-naive individuals showed even more marked and sustained superiority of the combination regimen over monotherapy (>1.8 log RNA copies/ml vs. 0.7 log RNA copies/ml aft er 4 weeks). These studies showed that the reductions in viral load ac hieved with combination therapies were greater and were sustained for longer periods than with monotherapy. The most pronounced effect was a chieved by the AZT/3TC combination. Assessment of viral load is a prac tical and promising approach to monitoring antiretroviral action.