Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Objective: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. Methods: HICs were identified in COHERE on the basis of \ue2\u89\ua55 consecutive viral loads (VL) \ue2\u89\ua4500 copies/mL over \ue2\u89\ua51 year whilst ART-naive, with the last VL \ue2\u89\ua4500 copies/mL measured \ue2\u89\ua55 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. Results: We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. Discussion: Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs

Long-term efficacy and safety of atazanavir/ritonavir treatment in a real-life cohort of treatment-experienced patients with HIV type 1 infection

A total of 381 Suffolk, Ile de France, Poll Dorset, Santa Ines and crossbred sheeps was used to investigate variability, genetic relationship, and the efficiency of protein polymorphisms in racial characterization and parentage tests. The genetic characterization was done through electrophoresis and by isoelectric focusing. The investigated loci presented 64.7% of variability. Two new alleles of Hemoglobin, HbA1 and HbB1, were detected in Santa Ines, Suffolk and crossbred animals. The allele M of glucose phosphate isomerase is, probably, a genetic marker for the Suffolk breed. The values of Nei's Diversity for the leucine amino peptidase, nucleoside phosphorilase, hemoglobin and malic enzyme loci were higher than the others, indicating higherspecificity in sheep breed characterization. Fisher's test revealed that allelic frequencies were different among breeds (P < 0.01), with the exceptions of the alleles phosphogluconate dehydrogenase and Catalase loci (P > 0.05). This genic differentiation was confirmed by multivariate analysis, which dendrogram, constructed from the genetic distances, showed two main clusters: one clusters the wool and the other the hairy breeds. In the first cluster, two distinct subgroups are observed: one represented by the specialized breeds Poll Dorset and Ile de France, and the other represented by the Suffolk group, demonstrating the genetic relationships among breeds. The efficiency of these markers to exclud one of two possible sires was 76.7, 68.0, 61.3 and 84.8 % for the Poll Dorset, Ile de France, Suffolk and Santa Ines breeds, respectively. The inclusion of other markers will increase the efficiency to 100% and will allow greater precision in investigation of paternity

Inter-laboratory comparison of HCV-RNA assay results: implications for multi-centre research

To investigate whether it is appropriate to assume comparability of hepatitis virus C (HCV)-RNA results across laboratories in multi-centre studies, nine laboratories of the European Paediatric HCV Network participated in an international proficiency study of HCV-RNA assays. A panel of 12 samples of different dilutions and genotypes was sent to each laboratory and tested with qualitative and/or quantitative HCV-RNA assays according to local procedures. Commercial assays were used in seven laboratories and in-house assays in two. All six laboratories in which a commercial qualitative assay was used were proficient, as were four of six runs (in five laboratories) in which a commercial quantitative assay was used. The proficiency of the laboratories where in-house assays were used could not be assessed according to the VQC definition because of differences in the methods used. Overall, there were several false-negative results, but only one false-positive result with a quantitative assay and none with a qualitative assay. The false-negative results may have implications for the diagnosis of infection, and highlight the need for an antibody test to be performed at 18 months to confirm the absence of infection. The results of qualitative assays were generally consistent across laboratories but it was difficult to evaluate and compare the results of quantitative assays, Multivariate analysis of data collected in multi-centre studies should therefore allow for centre and/or assay used