Phenotypic changes in drug susceptibility associated with failure of human immunodeficiency virus type 1 (HIV-1) triple combination therapy.
The emergence of drug-resistant human immunodeficiency virus type 1 is a frequent cause of failure of combination therapies comprising reverse transcriptase and protease inhibitors. Rational design of salvage therapies requires new methods to assess drug susceptibility. A novel phenotypic drug susceptibility assay was developed and used to measure the drug susceptibilities of viruses obtained from 2 patients treated with zidovudine, lamivudine, and nelfinavir. Results showed that phenotypic drug resistance may be detectable before virus load rebound, treatment failure does not always imply viral resistance to all drugs in a treatment regimen, and persons with similar antiviral treatment histories and clinical courses may have different phenotypic drug resistance profiles at the time that treatment fails.
Parkin
N T
NT
ViroLogic, Inc., South San Francisco, California 94080, USA. nparkin@virologic.com
Lie
Y S
YS
Hellmann
N
N
Markowitz
M
M
Bonhoeffer
S
S
Ho
D D
DD
Petropoulos
C J
CJ
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy*; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005838:Genotype; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D019888:Nelfinavir / Q000627:therapeutic use*; D010641:Phenotype; D016879:Salvage Therapy; D013997:Time Factors; D014162:Transfection; D017211:Treatment Failure; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D019888:Nelfinavir