Clinical significance of drug resistance in HIV-1 infection.
BACKGROUND
The limited duration of clinical benefit from nucleoside analogue therapy for HIV-1 infection may be explained, in part, by the emergence of virus isolates resistant to the drugs used. Additional reasons may include the presence of syncytium-inducing variants of HIV-1, progressive increase in viral load and progressive immunologic decline despite antiretroviral therapy.


CONCLUSIONS
Antiretroviral therapy may inevitably select for mutational changes in HIV-1 populations. However, recent advances in the understanding of drug resistance in HIV-1 infection suggest that, in certain cases, genotypic and phenotypic changes associated with drug resistance in vitro are not always synonymous with clinical drug failure. We consider the following examples: (1) the benefit of switching therapy may be independent of drug resistance; (2) patients may progress on therapy despite persistence of 'sensitive' virus; (3) drug susceptibility testing may underestimate the significance of drug resistance, and antiviral activity may persist despite resistance; and (4) resistance may be overcome with higher dosing.


CONCLUSIONS
Laboratory evidence for drug resistance does not necessarily imply clinical drug failure. Emergence of (-)-2',3-d-deoxy-3'-thiacytidine (3TC, lamivudine) resistance may potentiate activity of zidovudine in patients treated with 3TC/zidovudine combination therapy. Novel therapeutic strategies that exploit this mutational interaction, or challenge the limits of adaptation of the virus, may lead to more effective long-term suppression of HIV-1.
Kuritzkes
D R
DR
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver 80262, USA.
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004352:Drug Resistance, Microbial; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans
D019380:Anti-HIV Agents