AEGiS-15IAC: Extensive resistance testing during 5 years of lopinavir/ritonavir treatment in antiretroviral-naïve HIV infected patients: Results from study m97-720.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Extensive resistance testing during 5 years of lopinavir/ritonavir treatment in antiretroviral-naïve HIV infected patients: Results from study m97-720.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrB1291)

C Hicks¹, B da Silva², C Benson³, P Wolfe⁴, R Gulick⁵, M Glesby⁵, A C White⁶, R Murphy⁷, H Kessler⁸, M Albrecht⁹, M Thompson¹⁰, J Eron¹¹, K R King², F McMillan², S Brun², M King²
¹Duke University Medical Center, Durham, United States; ²Abbott Laboratories, Abbott Park, United States; ³University of Colorado, Denver, United States; ⁴Pacific Oaks Research, Beverly Hills, United States; ⁵Weill Medical College of Cornell University, New York, United States; ⁶Baylor College of Medicine, Houston, United States; ⁷Northwestern University, Chicago, United States; ⁸Rish University Medical College, Chicago, United States; ⁹Harvard University, Boston, United States; ¹⁰AIDS Research Consortium of Atlanta, Atlanta, United States; ¹¹University of North Carolina at Chapel Hill, Chapel Hill, United States

BACKGROUND: Study 720 is the longest-running study of lopinavir/ritonavir (LPV/r) therapy. Previous analyses of resistance in study 720 have been limited to patients meeting criteria for virologic failure. Results of resistance testing for patients with low-level viral rebound ("blips") is also of interest.

METHODS: In study 720, 100 antiretroviral (ARV)-naïve patients received LPV/r plus stavudine (d4T) and lamivudine (3TC). In this analysis,all patients with HIV RNA >500 copies/mL any time at or after Week 24 had samples submitted for genotypic testing. LPV resistance was defined as emergence of any primary or active site substitution in protease (positions 8,30,32,46,47,48,50,54,82,84,90). 3TC resistance was defined by the M184V/I mutation in reverse transcriptase (RT), and d4T resistance was defined as the emergence of any thymidine analog mutation (positions 41,67,70,210,215,219) in RT.

RESULTS: Median duration of follow-up is 281 weeks (5.4 years). At 252 weeks of follow-up, 64/100 (64%) patients had HIV RNA<50 copies/mL by intent-to-treat analysis (64/68 [94%], on-treatment analysis). A total of 34 samples from 27 patients who met the criteria defined above were submitted for resistance testing. Results were available from 22 (65%) samples in 17 patients. For 12 samples, testing failed due to low HIV RNA level (median 575, IQR 513-828 copies/mL). No patient (0/17) demonstrated LPV resistance or d4T resistance. 3TC resistance was observed in 3/17 patients (18%). Mean rebound HIV RNA level was 3.9 log₁₀ c/mL for patients with (n=3) or without (n=14) 3TC resistance (p=0.95). Among potential secondary mutations in protease, M36M/I emerged in 1 patient. No other new secondary mutations were observed.

CONCLUSIONS: Results of extensive genotypic resistance testing over more than 5 years confirm the absence of protease inhibitor resistance in ARV-naïve patients receiving LPV/r. Likewise, no genotypic resistance to d4T was observed, and 3TC resistance was uncommon.

Keywords: AEGIS, Ritonavir, HIV, Acquired Immunodeficiency Syndrome, Pyrimidinones, HIV Seropositivity, Stavudine, Lamivudine, Anti-HIV Agents, HIV Infections, HIV Protease Inhibitors, Drug Therapy, Combination, RNA-Directed DNA Polymerase, lopinavir, Humans, therapy, drug therapy

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WeOrB1291