Background:  To estimate the true rates of clinical outcomes from a recently completed 6-year dual protease inhibitor study, Kaplan-Meier conditional survival analysis allows the demonstration of cumulative rates of viral suppression with or without rebound, virologic failure, and study discontinuation. The study objectives are to illustrate  long-term durability, tolerability, and safety of RTV+SQV with and without NRTI intensification.

Methods:  An ongoing study of RTV+SQV was analyzed with follow-up to 5 years.  The primary outcome was suppression of plasma HIV RNA below 200 copies/mL.  A Kaplan-Meier survival analysis was conducted to evaluate time and cumulative rates of viral suppression, viral rebound, virologic failure, and study discontinuation for all patients.

Results: Of the original cohort, 120/139 (86%) patients with plasma HIV RNA >200 copies/mL at baseline experienced viral response <200 copies/mL during the study and   87/139 (63%) had either no rebound or viral re-suppression after experiencing rebound. Through year 5, 54/66 (82%) patients on study had viral response  <200 copies/mL with a median CD4 cell count increase of 381 cells/mm³ from baseline.  Median increase in CD4 cell count from year 4 to year 5 was 54 cells/mm³. While many elected intensification after 48 weeks to ensure continued viral suppression or at the investigator's discretion, 32/66 (48%) patients on study remain on RTV+SQV alone through year 5.   The percentage of NRTI-sparing and NRTI-intensified subjects with plasma HIV RNA < 200 copies/mL at year 5 was 88% and 84%, respectively. Between year 4 and year 5, 1/66 (2%) patients on study required initial NRTI-intensification and 17/83 (20%) patients discontinued, 3 due to adverse events, and 14 for other reasons.  No new safety issues have been identified.

Conclusions:   Final results in this study demonstrate that RTV/SQV dual PI therapy with or without NRTI intensification has durable activity and immunologic restoration through 5 years.