|
|
Genotyping and Phenotyping Analysis of B and Non-B HIV-1 Subtypes from Patients under HAART E. CARIDE*1, K. HERTOGS2, B. LARDER3, P. DEHERTOGH2, R. BRINDEIRO1, E. MACHADO5&6, C. A. M. DE SA4, W. A. EYER-SILVA4, F. S. SION4, L. F. C. PASSIONI5, J. A. MENEZES5, A. R. CALAZANS1, and A. TANURI1. 1Rio de Janeiro Federal Univ., Brazil; 2VIRCO, Mechelen, Belgium; 3VIRCO, Cambridge, UK; 4Hosp. Univ. Gaffrée & Guinle; 5Hosp. dos Servidores do Estado; and 6Hosp. Univ. Clementino Fraga Filho, Rio de Janeiro, Brazil Development of drug resistance remains one of the most serious obstacles to sustained suppression of virus plasma levels in HIV-1 infected patients treated with highly active antiretroviral therapy (HAART). Resistance mutations until now characterized were found in B-subtype viruses of developed countries. Resistance mutation profiles for non-B and more divergent B-subtype viruses found in developing countries shall be analyzed together with their ex vivo phenotyping, in order to establish a exact correlation between the genotyping data and the clinical management counseling for those exotic virus subtypes. In this work two groups of individuals were segregated based on viral load response after HAART. Fourteen were considered to have failed HAART therapy (HNR) and the remaining patients were grouped as HAART responders (HR). Proviral and plasma viral genomes were sequenced and subtyped. Phenotyping analysis for protease inhibitor susceptibility was performed using the recombinant virus assay technology. Non-B sequences were strongly associated with HNR group, and are likely to progress rapidly to resistance after HAART. In addition, a positive correlation between the time under HAART and lack of response to antiretroviral therapy was caused by subtype-B isolates inside the HNR group. Non-B subtypes do not present L90M and I84V mutations and used mainly G48V and V82A/F to achieve drug resistance. A strong cross-resistance phenotype among all four PI was associated to mutation L90M in the subtype-B isolates, and with G48V and V82A\F in non-B counterparts. These findings suggest that non-B subtype HIV-1 strains are less susceptible to HAART and use a different mutation pattern when compared to B isolates. This fact will impact the interpretation of the HIV genotypic tests when non-B isolates are analyzed and pose a major concern over the efficacy and lasting of combined anti-HIV therapy in countries which epidemic is driven by non-B subtype HIV-1 strains. Key Words: drug resistance, HIV-1, non-B subtypes |
|
© 7th
Conference on Retroviruses and Opportunistic Infections, |