Background:Potent combination antiretroviral therapy can reduce HIV plasma viral load (VL) to levels below the detection limit for as long as 2 years or more. A VL <500 HIV RNA copies/mL was until recently considered a reasonable therapeutic goal. However, lower levels seem necessary if VL rebounds and development of drug resistance are to be avoided.Patients and Methods:The clinical and virologic outcome at 1 year were prospectively examined in a group of 100 patients who began a triple combination antiretroviral therapy regimen consisting of stavudine (d4T), lamivudine (3TC), and indinavir (IDV). A modified ultrasensitive VL test with a detection limit of 40 copies/mL and a point mutation nested polymerase chain reaction (PCR) assay for detecting the codon 184 mutation conferring 3TC resistance were used for testing samples collected longitudinally from these individuals.Results:Overall, VL values <40 copies/mL were reached in 45% and 32% of patients at nadir and at 12 months, respectively. More than half (24 of 45 persons) who achieved a level <40 copies/mL at nadir remained with undetectable VL at 1 year, whereas this occurred in only one fourth (7 of 28 persons) of those having levels of 40 to 500 copies/mL (P< .05). However, rebounds in VL to >500 copies/mL at 1 year were seen at similar rates (26.6% and 25%, respectively) in persons achieving either complete (<40 copies/mL) or partial (40-500 copies/mL) VL suppression at nadir. In contrast, the codon 184 mutation emerged more frequently at 1 year in patients whose VL remained between 40 and 500 copies/mL at nadir than in those who reached a level <40 copies/mL (30.7% versus 0%;P< .05).Conclusion:Plasma VL at nadir after beginning highly active antiretroviral therapy (HAART) predicts the 1-year outcome. The achievement of levels of viremia <40 copies/mL are desirable during antiretroviral therapy if prolonged benefit is to be obtained. Because more than two thirds of persons with residual viremia do not show drug resistance, intensification strategies should be investigated for those patients with a good virologic response but without complete suppression during the first 6 months on HAART.Journal of Human Virology 1999;2:344-349 © Lippincott Williams & Wilkins, Inc.