Essential benefits of nucleoside analogue regimens in failing therapy.
Since the introduction of highly active antiretroviral therapy, nucleoside and more recently nucleotide reverse transcriptase inhibitors (NRTIs) have provided a highly effective backbone to antiretroviral regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Nonetheless, treatment failure can result from poor adherence, unfavourable pharmacokinetics, advanced disease or infection with a drug-resistant virus. Recent data have also indicated a high risk of virological failure with triple NRTI regimens, reflecting overall lower potency compared to combinations of NRTIs with either NNRTIs or PIs. Resistance mutations emerging upon failure can cause extensive cross-resistance among available NRTIs, and potentially affect susceptibility to newly developed antiretroviral drugs. However, despite the emergence of resistance, NRTIs can retain significant antiviral activity in treatment-experienced patients. This may reflect residual direct viral load suppression, as well as indirect effects related to impaired viral fitness of NRTI-resistant mutants and antagonist interactions between resistance mutations.
Geretti
Anna Maria
AM
Department of Virology, Royal Free Hospital and Royal Free & University College Medical School, Pond Street, London NW3 2QG, UK.
D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D017354:Point Mutation / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors