Recent advances in antiretroviral therapy and HIV infection monitoring.

Abstract

Potent new antiretroviral drugs combined with updated treatment strategies have now achieved efficient inhibition of HIV replication in most patients. The major targets for antiretroviral therapy are the reverse transcriptase and the protease of HIV. Up to date, 11 antiretroviral drugs have been licensed in the US. New nucleoside reverse transcriptase inhibitors (NRTI), i.e. abacavir, and adefovir dipivoxil proved to be effective in clinical trials. The antiretroviral activity and impact on clinical outcome of nonnucleoside reverse transcriptase inhibitors (NNRTI) are mostly short lived. Compared to NRTIs, protease inhibitors (PIs) have the highest antiretroviral activity. New PIs that conserve activity against mutant HIV strains or derivatives that have a simpler biosynthesis are being developed. A major drawback of highly active antiretroviral therapy is the selection of resistant mutants under suboptimal dosage, in advanced stages of disease or after pre-treatment with mono- or double-combination regimens. Monitoring of antiretroviral therapy is achieved by measurement of viral load using nucleic acid amplification techniques. The goal of antiretroviral therapy should be to reduce viral load below the detection limit of current assays in order to delay the emergence of resistant mutants and to maximally reduce disease progression. Recommendations for antiretroviral therapy and monitoring are evolving constantly due to the rapid progress in the development of active compounds and new insights into HIV pathogenesis. Resistance determination of HIV patient isolates seems to play a progressively increasing role in monitoring of antiretroviral treatment since treatment-naive patients may already harbour drug-resistant virus. Due to cross-resistance between different compounds, the choice of the treatment regimen should be guided by resistance patterns of HIV in order to warrant maximal and long-lasting efficiency.