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AIDS. 1996 Dec;10 Suppl 5:S27-31.

Clinical significance of drug resistance in HIV-1 infection.

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1
Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver 80262, USA.

Abstract

OVERVIEW:

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.

DISCUSSION:

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.

CONCLUSION:

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.

PMID:
9030393
[Indexed for MEDLINE]

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