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

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. HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 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. 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. 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

Adaptive Oblivious Transfer and Generalization

International audienceOblivious Transfer (OT) protocols were introduced in the seminal paper of Rabin, and allow a user to retrieve a given number of lines (usually one) in a database, without revealing which ones to the server. The server is ensured that only this given number of lines can be accessed per interaction, and so the others are protected; while the user is ensured that the server does not learn the numbers of the lines required. This primitive has a huge interest in practice, for example in secure multi-party computation, and directly echoes to Symmetrically Private Information Retrieval (SPIR). Recent Oblivious Transfer instantiations secure in the UC framework suf- fer from a drastic fallback. After the first query, there is no improvement on the global scheme complexity and so subsequent queries each have a global complexity of O(|DB|) meaning that there is no gain compared to running completely independent queries. In this paper, we propose a new protocol solving this issue, and allowing to have subsequent queries with a complexity of O(log(|DB|)), and prove the protocol security in the UC framework with adaptive corruptions and reliable erasures. As a second contribution, we show that the techniques we use for Obliv- ious Transfer can be generalized to a new framework we call Oblivi- ous Language-Based Envelope (OLBE). It is of practical interest since it seems more and more unrealistic to consider a database with uncontrolled access in access control scenarii. Our approach generalizes Oblivious Signature-Based Envelope, to handle more expressive credentials and requests from the user. Naturally, OLBE encompasses both OT and OSBE, but it also allows to achieve Oblivious Transfer with fine grain access over each line. For example, a user can access a line if and only if he possesses a certificate granting him access to such line. We show how to generically and efficiently instantiate such primitive, and prove them secure in the Universal Composability framework, with adaptive corruptions assuming reliable erasures. We provide the new UC ideal functionalities when needed, or we show that the existing ones fit in our new framework. The security of such designs allows to preserve both the secrecy of the database values and the user credentials. This symmetry allows to view our new approach as a generalization of the notion of Symmetrically PIR

Structure-Preserving Smooth Projective Hashing

International audienceSmooth projective hashing has proven to be an extremely useful primitive, in particular when used in conjunction with commitments to provide implicit decommitment. This has lead to applications proven secure in the UC framework, even in presence of an adversary which can do adaptive corruptions, like for example Password Authenticated Key Exchange (PAKE), and 1-out-of-m Oblivious Transfer (OT). However such solutions still lack in efficiency, since they heavily scale on the underlying message length. Structure-preserving cryptography aims at providing elegant and efficient schemes based on classical assumptions and standard group operations on group elements. Recent trend focuses on constructions of structure- preserving signatures, which require message, signature and verification keys to lie in the base group, while the verification equations only consist of pairing-product equations. Classical constructions of Smooth Projective Hash Function suffer from the same limitation as classical signatures: at least one part of the computation (messages for signature, witnesses for SPHF) is a scalar. In this work, we introduce and instantiate the concept of Structure- Preserving Smooth Projective Hash Function, and give as applications more efficient instantiations for one-round PAKE and three-round OT, and information retrieval thanks to Anonymous Credentials, all UC- secure against adaptive adversaries

Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

BACKGROUND: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD-program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS: Demographic, clinical and virological data from 4,140 antiretroviral-naive HIV-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002-2007. Baseline susceptibility to antiretroviral drugs was predicted using Stanford HIVdb v7.0. RESULTS: The overall prevalence of TDR did not change significantly over time and was 8.3% (95%CI 7.2-9.5) in 2008-2010. The most frequent indicators of TDR were NRTI-mutations (4.5%), followed by NNRTI-mutations (2.9%) and PI-mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine respectively, independent of current NRTI backbones. CONCLUSIONS: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affecte

HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings

HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings

The Most Common Comorbidities in Dandy-Walker Syndrome Patients: A Systematic Review of Case Reports.

OBJECTIVE: Dandy-Walker syndrome (DWS) is a rare neurologic multi-entity malformation. This review aimed at reporting its main nonneurologic comorbidities. METHODS: Following PRISMA guidelines, search in Medline was conducted (2000-2014, keyword: dandy-walker). Age, sex, country, DWS type, consanguinity or siblings with DWS, and recorded coexistent conditions (by ICD10 category) were extracted for 187 patients (46.5% male, 43% from Asia) from 168 case reports. RESULTS: Diagnosis was most often set in 12 years old (27.8%). One-third of cases had a chromosomal abnormality or syndrome (n = 8 PHACE), 27% had a cardiovascular condition (n = 7 Patent Ductus Arteriosus), 24% had a disease of eye and ear (n = 9 cataract); most common malignancy was nephroblastoma (n = 8, all Asian). Almost one-fifth had a mental illness diagnosis; only 6.4% had mild or severe intellectual disability. CONCLUSION: The spread of comorbidities calls for early diagnosis and multidisciplinary research and practice, especially as many cases remain clinically asymptomatic for years