Measuring viral load in the clinical setting.

The traditional approach of assessing new treatments in clinical end-point 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 methods of assessing the efficacy of antiretroviral regimens are necessary. Recently developed quantitative measures of viral nucleic acids are already proving invaluable in predicting which drugs and combinations are most promising for further investigation. These approaches have been used to evaluate the effect of antiretroviral drugs in clinical trials 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 approximately 50% in antiretroviral-naive patients on commencement of AZT monotherapy. For patients treated with AZT/ddI and AZT/ddC, reductions in serum HIV-1 RNA levels were significantly greater (80-90%). Increases in CD4 cell count corresponded with these decreases with the decrease in viral load. A second study (Trial NUCB3001) comparing the effect of AZT monotherapy 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 after 4 weeks). These studies showed that the reduction in viral load achieved with combination therapies were greater and were sustained for longer periods than with monotherapy. The most pronounced effect was achieved by the AZT/3TC combination. Assessment of viral load is a practical and promising approach to monitoring antiretroviral action.