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) geno typic 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 lev els <50 copies/ml were achieved in 17 (85%) of 20 combination-therapy patie nts 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-RTpatients had virus with M184V (lamuvidine resistance); 3 isolates also cont ained 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. R esults also indicate that combination regimens can fail despite the absence of detectable genotypic PR resistance.