Adherence with HIV antiviral regimens, particularly with the protease inhibitor (PI) is important to achieve HIV viral suppression. Complicated, multi-drug regimens can be difficult for patients to comply with and may affect outcomes. OBJECTIVE: To analyze adherence rates with 3-drug HIV regimens and assess the correlation of each regimen s adherence to HIV RNA values. METHODS: Medication adherence and HIV RNA levels were measured in 21 patients enrolled in clinical trials in a University-based HIV clinic. Data were collected at baseline, 2 weeks, at 4-week intervals for 24 weeks, and 8- to 12-week intervals thereafter for up to 96 weeks. Monthly medication adherence was calculated using pill counts. Plasma HIV RNA was measured by standard and ultrasensitive RT-PCR assay. All patients were on a PI plus 2NRTI regimen. PIs included saquinavir, indinavir, and nelfinavir. NRTIs included AZT, d4T, 3TC, and ddI. RESULTS: Patient adherence with PI therapy (86%) was found to be significantly lower (p=0.0001) than with NRTI1 (97.7%) and NRTI2 (100.4%). Adherence rates between NRTI1 and NRTI2 were not significantly different. All 3 drugs adherence rates were found to be negatively correlated to the log of the plasma HIV RNA level (PI R = -0.430, NRTI1 R= -0.181, NRTI2 R= -0.199). However, a linear regression model found that only PI adherence was a significant predictor of HIV RNA levels. CONCLUSION: This study indicates that adherence with the PI regimen was significantly lower than with nucleoside analogue compounds. The results also indicate that only adherence with the PI was a significant predictor of virologic response.