Emergence of a New Circulating B/CRF02/G Recombinant Form Spreading in France

International audienc

Full length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays

OBJECTIVE: There is evidence that gag contributes to protease inhibitor susceptibility in treatment-experienced patients. Moreover, protease inhibitor resistance-associated mutations can arise in gag in the absence of protease mutations in vitro. We wished to assess the contribution of full-length Gag to protease inhibitor susceptibility in viruses unexposed to protease inhibitors, in particular from the most common HIV-1 subtypes, namely subtype A and C. DESIGN: We compared the drug resistance profiles of subtype A and C cognate gag-protease (from viruses not previously exposed to protease inhibitor) to protease combined with a generic subtype B gag as in routine phenotypic testing. METHODS: We amplified gag-protease sequences from plasma-derived virus or molecular clones, and used a single cycle transfection-based drug resistance assay to compare the fold changes in the concentration of drug required to inhibit 50% of viral replication of these viruses to a generic subtype B. We made a series of chimeras to explore phenotypes further. RESULTS: In some cases, use of protease sequences without the cognate gag overestimated susceptibility to protease inhibitors, in particular to lopinavir. We provide evidence that gag sequences from wild-type viruses can contribute as much as 14-fold reduction in susceptibility to lopinavir, and that cognate protease can balance this by partially restoring susceptibility. CONCLUSION: Our findings demonstrate the importance of considering protease inhibitor susceptibility in the context of full-length gag, particularly with respect to the range of HIV-1 subtypes circulating worldwide

Evolutionary history of Podarcis tiliguerta on Corsica and Sardinia.

BACKGROUND: Podarcis tiliguerta is a wall lizard endemic to the Mediterranean islands of Corsica and Sardinia. Previous findings of high mtDNA and morphological diversity have led to the suggestion that it may represent a species complex. Here, we analysed mitochondrial and nuclear markers (mtDNA, 3110 bp; 6 nDNA loci, 3961 bp) in P. tiliguerta sampled from thirty-two localities across Corsica and Sardinia. RESULTS: We find much greater intraspecific genetic divergence than between sister species of other Mediterranean island Podarcis, i.e., between P. lilfordi and P. pityusensis. We detected three mtDNA clusters in Corsica (North, South-East and South-West) and either two or three in Sardinia (North vs. South) depending on the clustering method. Only one or two nDNA groups were identified within each main island (again, depending on the method). A Bayesian time-calibrated multispecies coalescent tree was obtained from mtDNA and provided statistical support for a Miocene origin of the species (13.87 Ma, 95% HPD: 18.30-10.77 Ma). The posterior mean divergence time for the Corsican and Sardinian lineages was 12.75 Ma ago (95% HPD: 16.94-9.04 Ma). CONCLUSION: The results support the evolutionary distinctiveness of Corsican and Sardinian populations and also indicate a lack of post-divergence migration despite periods of contact being possible. Further to this, species delimitation analyses of Corsican and Sardinian lineages provided statistical support for their recognition as distinct (sister) taxa. Our results provide new insights into the biogeography of the Mediterranean biodiversity hotspot, and contribute important findings relevant to the systematics and evolution of this speciose lizard genus

Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

<p>Abstract</p> <p>Background</p> <p>Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns.</p> <p>Patients and Methods</p> <p>We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing.</p> <p>Results</p> <p>Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%): drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available) and in newborn lymphocytes (6/8) suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10) and neonatal lymphocytes (2/8) suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped.</p> <p>Conclusion</p> <p>This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%), drug resistance was archived in the cellular reservoir and persisted during infancy, with or without antiretroviral treatment. This finding stresses the need for effective antiretroviral treatment of pregnant women.</p

Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.

In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure

Factors determining Gekkotan (Reptilia, Sauria) distribution in Tunisia (North Africa)

Tunisian geckos count nine species (1 is insular relict, 1 is endemic, 2 are ubiquitous and 5 are enfeoffed). We aim to determine factors influencing their distributions. Surveys were founded on environmental divisions. Presence/absence data for 113 grids were analyzed using multivariate tools. 18 environmental variables were revealed and clustered into five factors to model species distributions. Established models were further projected on non-explored areas within Tunisian territory. The distribution of continental geckos follows an indirect bidirectional gradient; the South-northward one is physiologically stressful and the North-southward one is biologically stressful. Five biogeographic regions were established showing concordance with climatic and vegetation regionalization. The distribution of non-anthropophilic species is positively correlated to thermal amplitudes gradient. The distribution of anthropophilic taxa is positively correlated to agricultural land-use. Oasis, sebkhas and chotts are particular landscapes that disturb both distributions. Predicted areas follow the yielded distribution patterns despite some discrepancy for S. sthenodactylus. The niche characterizing shows that land use and altitude increase the probability of occurrence of H. turcicus and T. mauritanica. Alternatively, they decrease the probability of the presence of T. deserti, T. neglecta, T. tripolitanus and S. petrii. Models could also show that the absence of S. sthenodactylus in northern regions is attributed to high altitudes and cereal land-use. As to T. fascicularis, the displacement of the northern limits of its range is mostly attributed to an improvement of field investigations. Established model of its distribution shows a restricted area of probable occurrence in central Tunisia confirming its endemism

Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children

<p>Abstract</p> <p>Background</p> <p>The impact of HIV drug resistance mutations in salvage therapy has been widely investigated in adults. By contrast, data available of predictive value of resistance mutations in pediatric population is scarce.</p> <p>Methods</p> <p>A multicenter, retrospective, observational study was conducted in children who received rescue salvage antiretroviral therapy after virologic failure. CD4 counts and viral load were determined at baseline and 6 months after rescue intervention. Genotypic HIV-1 resistance test and virtual phenotype were assessed at baseline.</p> <p>Results</p> <p>A total of 33 children met the inclusion criteria and were included in the analysis. The median viral load (VL) and median percentage of CD4+ at baseline was 4.0 HIV-RNA log copies/ml and 23.0% respectively. The median duration that children were taking the new rescue regimen was 24.3 weeks (23.8–30.6). Overall, 47% of the 33 children achieved virological response at 24 weeks. When we compared the group of children who achieved virological response with those who did not, we found out that mean number of PI related mutations among the group of responders was 3.8 <it>vs</it>. 5.4 (p = 0.115). Moreover, the mean number of susceptible drugs according to virtual phenotype clinical cut-off for maximal virologic response was 1.7 <it>vs</it>. 0.8 and mean number of susceptible drugs according to virtual phenotype cut-off for minimal virlologic response was 2.7 <it>vs</it>. 1.3 (p < 0.01 in all cases). Eighteen children were rescued with a regimen containing a boosted-PI and virological response was significantly higher in those subjects compared with the others (61.1% <it>vs</it>. 28.6%, p < 0.01).</p> <p>Conclusion</p> <p>Salvage treatment containing ritonavir boosted-PIs in children with virological failure was very efficient. The use of new tools as virtual phenotype could help to improve virologic success in pediatric population.</p

Discovery of an Italian slow worm (Anguis veronensis Pollini, 1818) population on a Western Mediterranean Island confirmed by genetic analysis

The genus Anguis is known to be mainly continental in the Mediterranean area, and accordingly it has never been recorded in Western Mediterranean islands. Here we report for the first time the presence of the slow worm in a Western Mediterranean island, the Ile Sainte-Marguerite from Lérins archipelago (southeastern France). The molecular analysis of ND2 and PRLR genes assigned the specimens to A. veronensis Pollini, 1818 and showed that they are genetically related to the mainland population from Les Mayons, in mainland France.

Impact of Low-Level-Viremia on HIV-1 Drug-Resistance Evolution among Antiretroviral Treated-Patients

to determine the emergence and evolution of DRAM during LLV in HIV-1-infected patients while receiving antiretroviral therapy (ART).Retrospective analysis of patients presenting a LLV episode defined as pVL between 40 and 500 c/mL on at least 3 occasions during a 6-month period or longer while on the same ART. Resistance genotypic testing was performed at the onset and at the end of LLV period. Emerging DRAM was defined during LLV if never detected on baseline genotype or before.48 patients including 4 naive and 44 pretreated (median 9 years) presented a LLV episode with a median duration of 11 months. Current ART included 2NRTI (94%), ritonavir-boosted PI (94%), NNRTI (23%), and/or raltegravir (19%). Median pVL during LLV was 134 c/mL. Successful resistance testing at both onset and end of the LLV episode were obtained for 37 patients (77%), among who 11 (30%) acquired at least 1 DRAM during the LLV period: for NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV period, number of drugs with genotypic resistance increased from a median of 4.5 to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART, current and nadir CD4 count, number of baseline DRAM and GSS were not identified as predictive factors of resistance acquisition during LLV, probably due to limited number of patients.Persistent LLV episodes below 500 c/ml while receiving ART is associated with emerging DRAM for all drug classes and a decreasing in further therapeutic options, suggesting to earlier consider resistance monitoring and ART optimization in this setting