Discordant genotypic interpretation and phenotypic role of protease mutations in HIV1 subtypesBandG
Abstract number: P1294
Santos A., Abecasis A., Vandamme A.M., Camacho R., Soares M.
HIV-1 group M is classified into nine different subtypes. Antiretroviral (ARV) drugs have been developed for subtype B, and the response of non-B subtypes in terms of susceptibility and the acquisition of drug resistance when facing those drugs is largely unknown. In this study, we wanted to address differences in the impact of protease inhibitor-selected mutations in subtypes B and G. ARV-treated, HIV-positive patients regularly followed at the Hospital de Egas Moniz, in Lisbon, Portugal, were examined for the presence of PI-associated primary mutations (301 of subtype B and 184 of subtype G), and for the selection of those mutations over time of protease inhibitor exposure. Forty-three subtype G patients were phenotyped for susceptibility to all available PI through VIRCO's Antivirogram®, and compared to a similar dataset of subtype B patients. Mutation I54V/L was selected by nelfinavir in subtype G isolates, a mutation not previously described for that drug in subtype B. L90M was associated with a lower reduction in susceptibility of subtype G to nelfinavir when compared with subtype B, and with no reduced susceptibility to saquinavir. This was compensated by the acquisition of M89I in subtype G. L90M did not reduce susceptibility of subtype G to saquinavir, contrarily to subtype B. Likewise, the pattern I54V/L-L90M did not reduce susceptibility of subtype G to indinavir and saquinavir. Indinavir-associated mutations M46I/L, I84V and V82A/F/T developed earlier in subtype B across length of exposure to that drug when compared to subtype G counterparts. Our results provide proof of principle and support the growing evidence that subtype-specific responses to ARV exist. Data presented here highlights inconsistencies in current genotyping interpretation algorithms inadequately applied to all HIV-1 subtypes.
|Session name:||19th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Helsinki, Finland, 16 - 19 May 2009|
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