439   Genotypic Resistance at Baseline Fails To Predict Outcome Among Chronically Infected, Antiretroviral-Therapy- Naive Patients in Two Large Trials of PI-Based Regimens.

A. T. Pavia*¹, R. Gulick², J. J. Eron³, K. Squires⁴, R. Murphy⁵, N. Schoellkopf⁶, N. Hellmann⁷, W. Huang⁶, N. Parkin⁷, R. A. Grosso⁷, and M. R. Stevens⁷for the Start I and Ii Protocol Teams.
¹Univ. of Utah, Salt Lake City;²Weill Med. Coll. of Cornell Univ., New York, NY;³Univ. of North Carolina, Chapel Hill;⁴Univ. of Southern California, Los Angeles;⁵Northwestern Univ., Chicago, IL;⁶PharmaRes., Morrisville, NC;⁷ViroLogic Inc., South San Francisco, CA; and⁷Bristol Myers Squibb, Plainsboro, NJ.

Background:Genotypic resistance testing predicts treatment outcome in treatment-experienced patients. In the absence of selective pressure, resistance may be underestimated. Therefore, these findings may not apply to chronically infected drug-naïve patients.

Methods:We studied the ability of baseline genotype to predict treatment outcome in 2 trials comparing AZT/ 3TC, D4T/3TC, or D4T/ddI, all in combination with indinavir among antiretroviral-naïve HIV-infected subjects. Patients were recruited during 1997-1998 at 30 centers. Baseline and failure isolates were sequenced from plasma samples. Sensitivity score and total mutations were calculated using the Resistance Collaborative Group data analysis plan. The association of resistance with virologic failure (confirmed VL >500c/mL) and time to failure was examined with logistic and Cox regression.

Results:Baseline genotypes are complete for 268 of 409 subjects. At least one significant resistance mutation (RCG criteria) was present in 5.2%, including M41L (1.9%), K70R (1.5%), T215R (0.4%) and M184V (0.4%). Prevalence varied by geographic site and was more common among gay men. 61 patients experienced virologic failure at wk 48; 27 (44%) developed M184V; 6 (10%) developed single PI mutations; 1 developed multiple PI mutations; and 25 (41%) had no mutations. Neither baseline genotypic resistance score nor the number of PI or NRTI mutations was predictive of failure at wk 24 or 48 or of time to failure.

Conclusions:In this population of chronically infected patients from across the U.S., resistance was uncommon. Genotypic resistance score and number of mutations were unable to predict failure at week 24 or 48 or time to failure. These data do not support the routine, non-selective use of baseline genotyping for chronically infected treatment-naïve patients.