Correlation between human immunodeficiency virus genotypic resistance and virologic response in patients receiving nelfinavir monotherapy or nelfinavir with lamivudine and zidovudine.
The relationship between detectable human immunodeficiency virus (HIV) genotypic resistance and virologic response was compared in patients receiving nelfinavir as monotherapy (16 weeks) or in combination with lamuvidine and zidovudine (48 weeks). Two patient groups were defined on the basis of the presence or absence of substitutions associated with nelfinavir, a protease (PR) inhibitor, and/or a reverse transcriptase (RT) inhibitor. HIV RNA levels <50 copies/mL were achieved in 17 (85%) of 20 combination-therapy patients without genotypic resistance (PR-RT(-)) versus only 1 (17%) of 6 patients with genotypic resistance (PR-RT(+)). PR-RT(-) patients exhibited greater and more durable virus suppression compared with PR-RT(+) patients. All 6 PR-RT(+) patients had virus with M184V (lamuvidine resistance); 3 isolates also contained D30N (nelfinavir resistance). M184V preceded D30N in all determinable instances. In this study, suppression of HIV replication to <50 copies/mL was associated with durable response and reduced incidence of resistance. Results also indicate that combination regimens can fail despite the absence of detectable genotypic PR resistance.
Agouron Pharmaceuticals, Inc., San Diego, California, 92121, USA.
B
B
Atkinson
J
J
Isaacson
M
M
Knowles
E
E
Mazabel
A K
AK
Patick
D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005838:Genotype; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D009154:Mutation; D019888:Nelfinavir / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D019888:Nelfinavir