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Background. The introduction of 2 or 3 fully active drugs in human immunodeficiency virus (HIV)-infected patients receiving failing antiretroviral therapy is a key determinant of subsequent treatment efficacy. The aim of this study was to assess the safety and efficacy of a regimen containing raltegravir, etravirine, and darunavir/ ritonavir for treatment-experienced patients infected with multidrug-resistant HIV. Methods. Patients enrolled in this phase II, noncomparative, multicenter trial were naive to the investigational drugs and had plasma HIV RNA levels 11000 copies/mL, a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors (NNRTI), ⩾3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) mutations, and ⩽3 darunavir and NNRTI mutations. The primary end point was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks. Results. A total of 103 patients enrolled in the study. At baseline, genotypic resistance profiles showed a median of 4 primary protease inhibitor mutations, 1 NNRTI mutation, and 6 NRTI mutations. In addition to the investigational drugs, 90 patients (87%) received optimized background therapy that included NRTIs (86 patients) or enfuvirtide (12 patients). At week 24, 90% of patients (95% confidence interval, 85%-96%) had an HIV RNA level <50 copies/mL. At week 48, 86% (95% confidence interval, 80%-93%) had an HIV RNA level <50 copies/ mL. The median CD4 cell count increase was 108 cells/mm3. Grade 3 or 4 clinical adverse events were reported in 15 patients (14.6%). Only 1 patient discontinued the investigational antiretroviral regimen, because of an adverse event. Conclusion. In patients infected with multidrug-resistant virus who have few remaining treatment options, the combination of raltegravir, etravirine, and darunavir/ritonavir is well tolerated and is associated with a rate of virologic suppression similar to that expected in treatment-naive patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]