Advances in antiretroviral therapy and viral load monitoring.

OBJECTIVE

To highlight recent developments in the field of antiretroviral therapy and viral load monitoring.

METHODS

Review of studies detailing the efficacy of the antiretroviral agents and combinations furthest along in clinical development and the application of plasma HIV RNA quantification as a disease marker.

RESULTS

Developments in the field of antiretroviral therapy have led to substantial advances in the approach to management of HIV-infected persons. These include the end of the zidovudine (ZDV) monotherapy era; the demonstration of a survival benefit conferred by antiretroviral therapy in patients with CD4 counts of 200-500x10(6)/l; the further development of newer nucleoside analog combinations (e.g., ZDV-lamivudine, stavudine-didanosine, stavudine-lamivudine, ZDV-1592U89) and the non-nucleoside reverse transcriptase inhibitor class of compounds; and, perhaps most importantly, the advent of the protease inhibitor era. Trials of ritonavir and saquinavir have proven that clinical benefit can be conferred by protease inhibitors, and three-drug combination regimens, such as indinavir-ZDV-lamivudine, have shown the potential for degrees of viral suppression not previously seen. Newer protease inhibitors, such as nelfinavir and VX-478/GW141W94, hold promise for further advances. The concurrent development of assays to quantitatively measure plasma HIV RNA has provided laboratory tools to improve our understanding of disease pathogenesis, to assess the in vivo potency of treatment regimens and to characterize the risk of disease progression.

CONCLUSIONS

Recent progress in HIV disease pathogenesis, antiretroviral therapy and viral load monitoring indicates the interdependence of these factors. The current optimism in the field is warranted but complex challenges must be met if the fulfilment of this hope is to be realized by the world community.