Maria de Fátima Gonçalves

HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing Regimen

To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.

Mutations selected in HIV-2-infected patients failing a regimen including atazanavir

OBJECTIVES To investigate mutations selected in viruses from HIV-2-infected patients failing a highly active antiretroviral treatment (HAART) regimen including atazanavir/ritonavir. METHODS Twenty-eight HIV-2-infected patients previously exposed to atazanavir/ritonavir and failing therapy were studied. The protease (PR) gene was amplified and sequenced, and mutations emerging under atazanavir/ritonavir selective pressure were reported. RESULTS The I50L mutation emerged in 4 out of 28 HIV-2-infected patients failing a HAART regimen including atazanavir/ritonavir. Besides I50L, four PR mutations previously associated with protease inhibitor resistance (I54L, I64V, V71I and I82F) and six PR mutations of unknown impact (V10I, E37D, S43T, K45R, I75V and F85L) in HIV-2 were also identified in this small group of patients. CONCLUSIONS Several mutations were associated with virological failure of a regimen including atazanavir/ritonavir in HIV-2-infected patients, including I50L for the first time. It should be included in HIV-2 algorithms for interpretation of genotypic resistance data, and taken into account when making therapeutic decisions for HIV-2-infected patients.

Assessment of the Cavidi ExaVir Load Assay for Monitoring Plasma Viral Load in HIV-2-Infected Patients

ABSTRACT HIV plasma viral load is an established marker of disease progression and of response to antiretroviral therapy, but currently there is no commercial assay validated for the quantification of viral load in HIV-2-infected individuals. We sought to make the first clinical evaluation of Cavidi ExaVir Load (version 3) in HIV-2-infected patients. Samples were collected from a total of 102 individuals living in Cape Verde, and the HIV-2 viral load was quantified by both ExaVir Load and a reference in-house real-time quantitative PCR (qPCR) used in Portugal in 91 samples. The associations between viral load and clinical prognostic variables (CD4+ T cell counts and antiretroviral therapy status) were similar for measurements obtained using ExaVir Load and qPCR. There was no difference between the two methods in the capacity to discriminate between nonquantifiable and quantifiable HIV-2 in the plasma. In samples with an HIV-2 viral load quantifiable by both methods (n = 27), the measurements were highly correlated (Pearson r = 0.908), but the ExaVir Load values were systematically higher relative to those determined by qPCR (median difference, 0.942 log10 copies/ml). A regression model was derived that enables the conversion of ExaVir Load results to those that would have been obtained by the reference qPCR. In conclusion, ExaVir Load version 3 is a reliable commercial assay to measure viral load in HIV-2-infected patients and therefore a valuable alternative to the in-house assays in current use.