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Session 13 Oral Abstract Session Antiretroviral Chemotherapy: Combination Therapy, Drug Resistance, and Treatment Interruption Session Time: Tuesday, 10 am - 12:30 pm Room 4B

11:15   46. Different Pathways to Nelfinavir Genotypic Resistance in HIV-1 Subtypes B and G P. Gomes, I. Diogo, M. F. Gonçalves, P. Carvalho, J. Cabanas, M. C. Lobo, and R. Camacho* Hosp. Egas Moniz, Lisbon, Portugal Background: Subtype G is the commonest non-B subtype in HIV-1-infected patients in Portugal (12% of the total number of infections). Although genotypic resistance to antiretroviral drugs has been extensively studied for HIV-1 subtype B, less is known about genotypic correlates for resistance on non-B subtypes. Our objective was to compare the genotypic patterns on nelfinavir failure in 2 groups of patients infected with a B or a G HIV-1 strain. Methods: 30 patients failing nelfinavir therapy as their first PI regimen were included; 19 were infected with HIV-1 subtype B, 11 with subtype G. Genetic sequence analysis was carried out using an automatic sequencer (ABI Prism 3100, Applied Biosystems, Foster City, CA). Resistance interpretation and subtyping was carried out using the Stanford HIV RT and Protease Sequence Database (http://hivdb.stanford.edu/hiv/). Statistical analysis was performed using the Mann-Whitney and Spearman rank-correlation tests. Results: 11 samples from patients of subtype B group and 10 of subtype G group exhibited genotypic correlates for nelfinavir resistance. 2 different pathways were detected: the classic one, involving the D30N mutation, and another one involving the L90M mutation. These 2 pathways appear to be mutually exclusive: no association of D30N and L90M was found in the same patient (Spearman r=-0.816, p<0,01). The D30N (p<0.01) pathway was only found on subjects infected with the subtype B strain (7/11); all the subtype-G-infected patients exhibited the L90M pathway or another set of mutations. Another significant observation was the presence of the I54V mutation, not commonly associated with nelfinavir resistance, in 6 of 10 subtype-G infected patients, whereas only in 1/11 in subtype-B group (P<0.05). Conclusions: HIV-1 subtype G apparently do not use the classic pathway to nelfinavir resistance with the D30N mutation, using another involving the L90M mutation. The presence of this mutation can increase cross-resistance with other drugs on the PI class: cross-resistance can be further enhanced by the presence of the I54V mutation, significantly present on the subtype G patients included in this study. The full implications of this observations should be assessed in a larger, prospective, randomized study.

©2002 9th Conference on Retroviruses and Opportunistic Infections