AEGiS-15IAC: Virological response and resistance to Lopinavir/Ritonavir in non-B HIV-I patients.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Virological response and resistance to Lopinavir/Ritonavir in non-B HIV-I patients.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. B10322)

Grossman Z, Lorber M, Shahar E, Torten D, Levi I, Risenberg K, Chowers M, Istomin V, Averbuch D, Burke M, Engelhard D, Sthoeger Z, Pollack S, Kra-Oz Z, Ram D, Rudich H, Mileguir F, Mendelson E, Maayan S, Schapiro JM
National HIV Reference Lab, PHL, MOH, Tel Hashomer, Israel

BACKGROUND: An algorithm based on the number of specific subtype-B protease gene mutations is commonly used to interpret resistance assay results and predict the response to LPN/RTN. Subtle differences present in the protease gene of non-subtype B patients might influence resistance to LPN/RTN. We compared virological response drug levels and genotypic resistance to LPN/RTN in B and non-B patients.

METHODS: Protease of all samples from infected patients receiving LPN/RTN with HIV RNA>1000 copies/ml was genotyped. Mutations score was calculated based on the standard algorithm. Evolution of mutations and immunologic and virologic outcome were traced longitudinally. Results were compared between B and non-B infected patients. RESULTS: Samples from 25 non-B and 23 B LPN/RTN treated patients were analyzed. Patients were receiving LPN/RTN for a mean of 11.7 months. Mean log HIV RNA levels (cp/ml) were 5.38 B, 5.13 non-B. Mean CD4 counts (cells/il) were 197 B, 174 non-B. Mean Cmin LPN levels (ng/ml) were 8,216 B, 8,716 non-B. All mutations included in the standard LPN/RTN algorithm were detected in non-B patients with the following prevalence: 10 (44%), 20 (60%), 24 (8%), 46 (32%), 53 (4%), 54 (28%), 63 (56%), 71 (20%), 82 (32%), 84 (8%) & 90 (24%). The mean score was 3.16 for non-B and 4.0 for B (p=0.76). Mutations M36I and I93L were present in all non-B patients but are not included in the score. These baseline polymorphisms are maintained throughout successive PI treatment regimens. HIV RNA remained reduced in both B and non-B compared to pre-LPN/RNA values.

CONCLUSION: All common LPN/RTN associated mutations can be found in non-B patients exposed to the drug. The lower mean score calculated for non-B patients might be due to the impact of baseline polymorphisms at positions 36 and/or 93 that are more commonly seen in non-B but are presently not included in the score. Our data strongly support the use of LPN/RTN in non-B patients

Keywords: AEGIS, Ritonavir, HIV-1, Pyrimidinones, HIV Protease, HIV Protease Inhibitors, HIV Infections, Anti-HIV Agents, CD4 Lymphocyte Count, HIV-1 Reverse Transcriptase, HIV, Genotype, Acquired Immunodeficiency Syndrome, Mutation, Prevalence, lopinavir, Humans, virology, genetics

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B10322