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We studied seven heavily pretreated HIV-2-infected patients exhibiting a virological failure while receiving a salvage raltegravir-containing regimen. At the time of virological failure, different resistance genetic pathways were observed: T97A-Y143C, Q148K, Q148R, G140S-Q148R, E92Q-Y143R-N155H, and T97A-N155H. Thus, despite a 40% difference in integrase genes between HIV-1 and HIV-2, the genetic pathways leading to raltegravir resistance are similar.

Objectives: We investigated the in vitro phenotypic susceptibility of HIV-2 isolates from integrase inhibitor (INI)-naive patients to INIs and its relation to HIV-2 integrase gene polymorphism., Methods: We determined the phenotypic susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values were compared with those for HIV-1 reference strains. HIV-2 integrase gene polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the French HIV-2 cohort., Results: Median raltegravir and elvitegravir IC(50) values for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38% of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the HHCC and RKK motifs were fully conserved, at the same genomic positions as described in HIV-1. In subtype B isolates, the total length of the integrase gene varied, owing to the presence of stop codons at positions 288, 294, 297 and 302. Fourteen of the positions associated with substitutions conferring INI resistance in HIV-1 were polymorphic in HIV-2., Conclusions: Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.

We determine phenotypic susceptibility of human immunodeficiency virus type 2 (HIV-2) isolates to amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, saquinavir, and tipranavir. Saquinavir, lopinavir, and darunavir are potent against wild-type HIV-2 isolates and should be preferred as first-line options for HIV-2-infected patients. Other protease inhibitors are less active against HIV-2 than against HIV-1.

Abstract: Human immunodeficiency viruses HIV-1 and HIV-2 are the results of multi-interspecies transmissions from simian virus to humans. HIV-1 viruses are very divergent and are classified in three groups: M, N and O. The group M is subdivided in nine subtypes and numerous Circulating Recombinant Forms. In 1996, protease inhibitors and HAART disposal have modified the prognostic of the HIV infection. However, one of the major problems is the emergence of antiretroviral resistance. A major advance from the last year is the access to antiretroviral in resources limited countries. On the other hand, the development of a vaccine is today hypothetic. [Copyright &y& Elsevier]