Broad Nucleoside Reverse-Transcriptase Inhibitor Cross-Resistance in Human Immunodeficiency Virus Type 1 Clinical Isolates

Nucleoside reverse-transcriptase inhibitors (NRTIs) are important components of most antiretroviral combination treatment regimens. Using a large collection of clinical isolates, we characterized patterns of cross-resistance among all NRTIs. Drugs were grouped by the effect of the M184V mutation: su...

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Bibliographic Details
Published in:The Journal of infectious diseases 2003-10, Vol.188 (7), p.992-1000
Main Authors: Whitcomb, Jeannette M., Parkin, Neil T., Chappey, Colombe, Hellmann, Nicholas S., Petropoulos, Christos J.
Format: Article
Language:English
Subjects:
Anti-HIV Agents - therapeutic use
Antiretrovirals
Antivirals
Biological and medical sciences
Correlations
Cross resistance
Drug Resistance, Multiple, Viral
Fundamental and applied biological sciences. Psychology
HIV
HIV 1
HIV Infections - virology
HIV Reverse Transcriptase - antagonists & inhibitors
HIV Reverse Transcriptase - genetics
HIV-1 - drug effects
HIV-1 - enzymology
HIV-1 - genetics
HIV-1 - isolation & purification
HIV/AIDS
Human viral diseases
Humans
Infectious diseases
Medical sciences
Microbiology
Miscellaneous
Nucleosides
Point Mutation
Reverse transcriptase inhibitors
Reverse Transcriptase Inhibitors - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Viral - chemistry
RNA, Viral - genetics
Sequence Analysis, DNA
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Virology
Viruses
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Summary:Nucleoside reverse-transcriptase inhibitors (NRTIs) are important components of most antiretroviral combination treatment regimens. Using a large collection of clinical isolates, we characterized patterns of cross-resistance among all NRTIs. Drugs were grouped by the effect of the M184V mutation: susceptibility to group 1 drugs (zidovudine, stavudine, tenofovir, and adefovir) increased when M184V was present, whereas susceptibility to group 2 drugs (didanosine, zalcitabine, abacavir, and lamivudine) decreased. Significant cross-resistance was observed among all NRTIs and was most notable when samples with or without M184V were analyzed separately. An increasing number of thymidine-analogue mutations (TAMs) was associated with a progressive reduction in drug susceptibility for all NRTIs. The modulating effect of M184I/V on drug susceptibility was present regardless of the number of TAMs. The broad range of susceptibility observed for viruses containing the same number of TAMs indicates that the genetic correlates of NRTI resistance remain to be fully elucidated
ISSN:0022-1899
1537-6613
DOI:10.1086/378281