Role of Advanced Hemodynamic Ultrasound Evaluation in the Differential Diagnosis of Middle Cerebral Artery Stenosis: Introducing Morphological Criteria.

OBJECTIVE: The aim of the work described here was to determine the possible impact of the new technique advanced hemodynamic ultrasound evaluation (AHUSE) in identification of severe intracranial stenosis. Transcranial Doppler (TCD) and transcranial color-coded Doppler (TCCD) provide reliable velocimetric data, the indirect analysis of which allows us to obtain information on the patency of vessels and assumed stenosis range. However, very tight stenoses (>95%) cannot be detected with velocimetric criteria because of spectrum drops and the absence of high velocities, so that the right curve of the Spencer equation cannot be solved. Likewise, high velocities are not detected when analyzing morphologically long stenosis. Furthermore, the current classifications based on velocimetric criteria do not provide any categorization on stenoses with multiple acceleration points (MAPs). METHODS: With this Technical Note we aim to introduce, in addition to velocimetric criteria, more morphological criteria based on TCCD with the algorithm of AHUSE to optimize the characterization of intracranial stenosis (IS). TCCD-AHUSE relies on intensity-based next-generation techniques and can be used to identify IS with MAPs and simultaneously perform a morphological assessment of the stenosis length. RESULTS: We introduce a new technical ultrasound (U) approach that we tested in a sample of four different types of stenoses combining velocimetric data and AHUSE using Esaote Microvascularization (MicroV) technique to the M1 tract of the middle cerebral artery (MCA). CONCLUSION: The authors believe that a multiparametric evaluation is more sensitive and supports the clinician by introducing the morphological concept, not just the velocimetric concept, to differentiate the IS pattern of MCA. The potential for developing a diagnostic/prognostic algorithm is discussed.

Spontaneous chronic subdural hematoma as the cause of oculomotor cranial nerve palsy: A narrative review.

Acute complete third nerve palsy with pupillary involvement is usually caused by a posterior communicating artery aneurysm (i.e. "the rule of the pupil"). The pupillary fibers run peripherally in the third nerve and are thus susceptible to the external compression. Headache is usually present, and urgent diagnosis and treatment are warranted. Rarely, however, neuroimaging shows other causes of third nerve palsy. In this study, we perform a literature review of spontaneous chronic subdural hematoma that, although rarely, may cause an acute pupil-involving third nerve palsy as a false localizing sign. We review the localizing, nonlocalizing, and false localizing nature of ocular motor cranial nerve palsy in this setting.

"Go", "No Go," or "Where to Go"; does microbiota dictate T cell exhaustion, programming, and HIV persistence?

PURPOSE OF REVIEW: People living with HIV who fail to fully reconstitute CD4+T cells after combination antiretroviral therapy therapy (i.e. immune nonresponders or INRs) have higher frequencies of exhausted T cells are enriched in a small pool of memory T cells where HIV persists and have an abundance of plasma metabolites of bacterial and host origins. Here, we review the current understanding of critical features of T cell exhaustion associated with HIV persistence; we propose to develop novel strategies to reinvigorate the effector function of exhausted T cells with the aim of purging the HIV reservoir. RECENT FINDINGS: We and others have recently reported the role of microbiota and metabolites in regulating T cell homeostasis, effector function, and senescence. We have observed that bacteria of the Firmicute phyla (specifically members of the genus Lactobacilli), associated metabolites (ß-hydroxybutyrate family), and bile acids can promote regulatory T cell differentiation in INRs with a senescent peripheral blood gene expression profile. SUMMARY: The cross-talk between immune cells and gut microbes at the intestinal mucosa (a major effector site of the mucosal immune response), regulates the priming, proliferation, and differentiation of local and distant immune responses. This cross-talk via the production of major metabolite families (like serum amyloid A, polysaccharide A, and aryl hydrocarbon receptor ligands) plays a key role in maintaining immune homeostasis. HIV infection/persistence leads to gut dysbiosis/microbial translocation, resulting in the local and systemic dissemination of microbes. The ensuing increase in immune cell-microbiome (including pathogens) interaction promotes heightened inflammatory responses and is implicated in regulating innate/adaptive immune effector differentiation cascades that drive HIV persistence. The exact role of the microbiota and associated metabolites in regulating T cell- mediated effector functions that can restrict HIV persistence continue to be the subject of on-going studies and are reviewed here.

Utilizing Computational Machine Learning Tools to Understand Immunogenic Breadth in the Context of a CD8 T-Cell Mediated HIV Response.

Predictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals within a population and consideration of sequence diversity in the context of an individual's CD8 T-cell immune repertoire to assess the HIV proteome for defined regions of immunogenicity. Using this approach, analysis of HLA adaptation and functional immunogenicity data enabled the identification of regions within the proteome that offer significant conservation, HLA recognition within a population, low prevalence of HLA adaptation and demonstrated immunogenicity. We believe this unique and novel approach to vaccine design as a supplement to vitro functional assays, offers a bespoke pipeline for expedited and rational CD8 T-cell vaccine design for HIV and potentially other pathogens with the potential for both global and local coverage.

Resistance profile of HIV-1 quasispecies in patients under treatment failure using single molecule, real-time sequencing.

OBJECTIVE: Short-read next-generation sequencing (NGS) has been implemented to study the resistance profile of HIV as it provides a higher sensitivity than Sanger sequencing. However, short-reads only generates a consensus view of the viral population rather than a reconstruction of the viral haplotypes. In this study, we evaluated the resistance profile of HIV quasispecies in patients undergoing treatment failure using SMRT sequencing. DESIGN: Whole-pol RT-PCR was performed on viral RNA extracted from plasma samples of 38 HIV-positive individuals undergoing treatment failure, and sequenced in the RSII instrument. Error correction and viral haplotype phasing was performed with the Multilayer Directed Phasing and Sequencing (MDPSeq) algorithm. Presence of resistance mutations reported by the IAS-USA in 2017 was assessed using an in-house script. RESULTS: The SMRT sequencing-based test detected 131/134 resistance mutations previously detected using a Sanger sequencing-based test. However, the SMRT test also identified seven additional mutations present at an estimated frequency lower than 30%. The intra-host phylogenetic analysis showed that seven samples harbored at least one resistance variant at 20--80% frequency. The haplotype-resolved sequencing revealed viral diversification and selection of new resistance during suboptimal treatment, an overall trend toward selection and accumulation of new resistance mutations, as well as the co-existence of resistant and susceptible variants. CONCLUSION: Our results validate the SMRT sequencing-based test for detection of HIV drug resistance. In addition, this method unraveled the complex dynamic of HIV quasispecies during treatment failure, which might have several implications on clinical management.

Rivaroxaban in cervical and "cervico-cerebral" artery dissections: a new therapeutic option?

Antiplatelet agents and vitamin K antagonists (VKA) are usually used in the treatment of cervical (carotid or vertebral) artery dissections (CADs); however, data about the use of direct oral anticoagulants (DOACs) in these conditions are very limited. DOACs have proven to be effective in stroke reduction in non-valvular atrial fibrillation and, when possible, they are preferred to warfarin because of their better safety profile. We describe four cases of CADs and, firstly in literature, cervico-cerebral (CCADs) in young patients (average age of 42 years) treated with rivaroxaban 20 mg daily. Three of these four dissections had affected the vertebral artery (condition with an unfavorable prognosis and more often complicated by subarachnoid hemorrhages), and the other one was a carotid dissection at the extra-intracranial passage. All patients were followed clinically and with serial neurosonological examinations at 1, 3, and 6 months and with magnetic resonance angiography (MRA) at 6 months. All patients presented a good outcome with vascular recanalization without stroke recurrence or bleedings, even in patients with intracranial vertebral artery involvement. DOACs could be an alternative in young patients with CADs and their use could be considered in intracranial artery dissections too.

The predictive power of transcranial sonography in movement disorders: a longitudinal cohort study.

Transcranial sonography (TCS) is a noninvasive, easily performed, and commonly available neuroimaging technique useful for the study of brain parenchyma in movement disorders. This tool has been increasingly used in the diagnosis of Parkinson's disease and atypical parkinsonism. The aim of the study was to evaluate the applicability of this technique as supportive tool in the early diagnosis of movement disorders. We performed TCS on 315 individuals which were diagnosed as healthy controls or affected by idiopathic Parkinson's disease, monogenetic subtypes of Parkinson's disease, atypical parkinsonism, and Dementia with Lewy bodies. Five TCS diagnostic patterns were defined on the basis of substantia nigra's and lenticular nuclei's echogenicity. TCS evaluations were performed by two blinded neuro-sonographers. Clinical diagnosis on all individuals was performed at baseline and at 4-year follow-up. The concordance rate between TCS patterns and clinical diagnosis and the specificity of TCS pattern to discriminate each group of individuals were compared at baseline and at follow-up. The concordance rate between TCS patterns and clinical diagnosis of all individuals was 84% at baseline and increased at follow-up (91%) significantly (p = 0.01). The specificity of TCS pattern in the comparison between patients diagnosed as affected by idiopathic Parkinson's disease and atypical parkinsonism showed a significant increase at follow-up (p = 0.03). Our study strongly confirms the role of TCS as a noninvasive and cost-effective tool in early diagnosis of movement disorders.

MicroV Technology to Improve Transcranial Color Coded Doppler Examinations.

The purpose of this review is to provide an update on technology related to Transcranial Color Coded Doppler Examinations. Microvascularization (MicroV) is an emerging Power Doppler technology which can allow visualization of low and weak blood flows even at high depths, thus providing a suitable technique for transcranial ultrasound analysis. With MicroV, reconstruction of the vessel shape can be improved, without any overestimation. Furthermore, by analyzing the Doppler signal, MicroV allows a global image of the Circle of Willis. Transcranial Doppler was originally developed for the velocimetric analysis of intracranial vessels, in particular to detect stenoses and the assessment of collateral circulation. Doppler velocimetric analysis was then compared to other neuroimaging techniques, thus providing a cut-off threshold. Transcranial Color Coded Doppler sonography allowed the characterization of vessel morphology. In both Color Doppler and Power Doppler, the signal overestimated the shape of the intracranial vessels, mostly in the presence of thin vessels and high depths of study. In further neurosonology technology development efforts, attempts have been made to address morphology issues and overcome technical limitations. The use of contrast agents has helped in this regard by introducing harmonics and subtraction software, which allowed better morphological studies of vessels, due to their increased signal-to-noise ratio. Having no limitations in the learning curve, in time and contrast agent techniques, and due to its high signal-to-noise ratio, MicroV has shown great potential to obtain the best morphological definition.

HLA Class I Downregulation by HIV-1 Variants from Subtype C Transmission Pairs.

HIV-1 downregulates human leukocyte antigen A (HLA-A) and HLA-B from the surface of infected cells primarily to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface and bind inhibitory killer immunoglobulin-like receptors, preventing natural killer (NK) cell-mediated suppression. However, a recent study found HIV-1 primary viruses have the capacity to downregulate HLA-C. The goal of this study was to assess the heterogeneity of HLA-A, HLA-B, and HLA-C downregulation among full-length primary viruses from six chronically infected and six newly infected individuals from transmission pairs and to determine whether transmitted/founder variants exhibit common HLA class I downregulation characteristics. We measured HLA-A, HLA-B, HLA-C, and total HLA class I downregulation by flow cytometry of primary CD4 T cells infected with 40 infectious molecular clones. Primary viruses mediated a range of HLA class I downregulation capacities (1.3- to 6.1-fold) which could differ significantly between transmission pairs. Downregulation of HLA-C surface expression on infected cells correlated with susceptibility to in vitro NK cell suppression of virus release. Despite this, transmitted/founder variants did not share a downregulation signature and instead were more similar to the quasispecies of matched donor partners. These data indicate that a range of viral abilities to downregulate HLA-A, HLA-B, and HLA-C exist within and between individuals that can have functional consequences on immune recognition.IMPORTANCE Subtype C HIV-1 is the predominant subtype involved in heterosexual transmission in sub-Saharan Africa. Authentic subtype C viruses that contain natural sequence variations throughout the genome often are not used in experimental systems due to technical constraints and sample availability. In this study, authentic full-length subtype C viruses, including transmitted/founder viruses, were examined for the ability to disrupt surface expression of HLA class I molecules, which are central to both adaptive and innate immune responses to viral infections. We found that the HLA class I downregulation capacity of primary viruses varied, and HLA-C downregulation capacity impacted viral suppression by natural killer cells. Transmitted viruses were not distinct in the capacity for HLA class I downregulation or natural killer cell evasion. These results enrich our understanding of the phenotypic variation existing among natural HIV-1 viruses and how that might impact the ability of the immune system to recognize infected cells in acute and chronic infection.

Effects of different ozonized slurry-ice treatments and superchilling storage (-1°C) on microbial spoilage of two important pelagic fish species.

Combining different preservative treatments for improving quality and safety of fishery products increasingly receives global research attention. Consistent with this pursuit, the current research was undertaken to determine the effects of different ozonized slurry-ice treatments and superchilling (-1°C) storage on microbial spoilage of European anchovy (Eugraulis encrasicolus) and sardine (Sardina pilchardus), which are two commercially important pelagic fish species. After the catch (within <5 hr) and at defined scheduled storage times, ozone has been discharged once on sardine (herein referred to as "One-T") and repeatedly/sequentially on European anchovy (herein referred to as "Seq-T"). Microbiological analyses enumerated total viable count (TVC), Bacillus spp., Enterobacteriaceae, Lactobacillus spp., Moraxella spp., Shewanella spp., Listeria monocytogenes and Pseudomonas spp. Independent of potential antimicrobial effects of ozone during superchilling storage, no Listeria spp., Shewanella spp., Moraxella spp., and Bacillus spp. were found in all processed samples. While Enterobacteriaceae and Lactobacillus spp. were detected at below 1 log cfu/g, both TVC and Pseudomonas spp. proliferated at different rates throughout superchilling storage. The repeated ozone-treated ("Seq-T") showed lower TVC and Pseudomonas spp. values compared with one-time treated ("One-T") slurry-iced and control samples. Thus, combined slurry-ice and superchilling storage at Seq-T produced improved antimicrobial activity over One-T application. Largely, ozonized slurry-ice outcomes/results appear promising thanks to superchilling storage.

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial).

BACKGROUND AND PURPOSE: Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. METHODS: According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. RESULTS: We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60-1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). CONCLUSIONS: Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.

Virus-Host Gene Interactions Define HIV-1 Disease Progression.

In this chapter, we will review recent research on the virology of HIV-1 transmission and the impact of the transmitted virus genotype on subsequent disease progression. In most instances of HIV-1 sexual transmission, a single genetic variant, or a very limited number of variants from the diverse viral quasi-species present in the transmitting partner establishes systemic infection. Transmission involves both stochastic and selective processes, such that in general a minority variant in the donor is transmitted. While there is clear evidence for selection, the biological properties that mediate transmission remain incompletely defined. Nevertheless, the genotype of the transmitted founder virus, which reflects prior exposure to and escape from host immune responses, clearly influences disease progression. Some escape mutations impact replicative capacity, while others effectively cloak the virus from the newly infected host's immune response by preventing recognition. It is the balance between the impact of escape mutations on viral fitness and susceptibility to the host immunogenetics that defines HIV-1 disease progression.

Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression.

HIV-1 adapts to a new host through mutations that facilitate immune escape. Here, we evaluate the impact on viral control and disease progression of transmitted polymorphisms that were either preadapted to or nonassociated with the new host's HLA. In a cohort of 169 Zambian heterosexual transmission pairs, we found that almost one-third of possible HLA-linked target sites in the transmitted virus Gag protein are already adapted, and that this transmitted preadaptation significantly reduced early immune recognition of epitopes. Transmitted preadapted and nonassociated polymorphisms showed opposing effects on set-point VL and the balance between the two was significantly associated with higher set-point VLs in a multivariable model including other risk factors. Transmitted preadaptation was also significantly associated with faster CD4 decline (<350 cells/µl) and this association was stronger after accounting for nonassociated polymorphisms, which were linked with slower CD4 decline. Overall, the relative ratio of the two classes of polymorphisms was found to be the major determinant of CD4 decline in a multivariable model including other risk factors. This study reveals that, even before an immune response is mounted in the new host, the balance of these opposing factors can significantly influence the outcome of HIV-1 infection.

Multiplexed highly-accurate DNA sequencing of closely-related HIV-1 variants using continuous long reads from single molecule, real-time sequencing.

Single Molecule, Real-Time (SMRT) Sequencing (Pacific Biosciences, Menlo Park, CA, USA) provides the longest continuous DNA sequencing reads currently available. However, the relatively high error rate in the raw read data requires novel analysis methods to deconvolute sequences derived from complex samples. Here, we present a workflow of novel computer algorithms able to reconstruct viral variant genomes present in mixtures with an accuracy of >QV50. This approach relies exclusively on Continuous Long Reads (CLR), which are the raw reads generated during SMRT Sequencing. We successfully implement this workflow for simultaneous sequencing of mixtures containing up to forty different >9 kb HIV-1 full genomes. This was achieved using a single SMRT Cell for each mixture and desktop computing power. This novel approach opens the possibility of solving complex sequencing tasks that currently lack a solution.

HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck.

Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naïve recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.

Estimation of HIV-testing rates to maximize early diagnosis-derived benefits at the individual and population level.

BACKGROUND: In HIV infection, initiation of treatment is associated with improved clinical outcom and reduced rate of sexual transmission. However, difficulty in detecting infection in early stages impairs those benefits. We determined the minimum testing rate that maximizes benefits derived from early diagnosis. METHODS: We developed a mathematical model of HIV infection, diagnosis and treatment that allows studying both diagnosed and undiagnosed populations, as well as determining the impact of modifying time to diagnosis and testing rates. The model's external consistency was assessed by estimating time to AIDS and death in absence of treatment as well as by estimating age-dependent mortality rates during treatment, and comparing them with data previously reported from CASCADE and DHCS cohorts. RESULTS: In our model, life expectancy of patients diagnosed before 8 years post infection is the same as HIV-negative population. After this time point, age at death is significantly dependent on diagnosis delay but initiation of treatment increases life expectancy to similar levels as HIV-negative population. Early mortality during HAART is dependent on treatment CD4 threshold until 6 years post infection and becomes dependent on diagnosis delay after 6 years post infection. By modifying testing rates, we estimate that an annual testing rate of 20% leads to diagnosis of 90% of infected individuals within the first 8.2 years of infection and that current testing rate in middle-high income settings stands close to 10%. In addition, many differences between low-income and middle-high incomes can be predicted by solely modifying the diagnosis delay. CONCLUSIONS: To increase testing rate of undiagnosed HIV population by two-fold in middle-high income settings will minimize early mortality during initiation of treatment and global mortality rate as well as maximize life expectancy. Our results highlight the impact of achieving early diagnosis and the importance of strongly work on improving HIV testing rates.

Updates on Somatoform Disorders (SFMD) in Parkinson's Disease and Dementia with Lewy Bodies and discussion of phenomenology.

Somatoform Disorders (SFMD) were recently described in Parkinson Disease (PD) and Dementia with Lewy Bodies (DLB). The present paper updates the observations in our cohort of patients and further details clinical phenomenology. Of 3178 patients consecutively referred to our Institutions from 1999, 1572 subjects had neurodegenerative diseases and 1718 psychiatric disorders. After 2-9 years of follow up, 488 patients were labelled as PD, 415 as Alzheimer Disease, 162 as DLB, 48 as Progressive Supranuclear Palsy, 48 as Multiple System Atrophy and 49 as Fronto-Temporal Dementia. The frequency of SFMD (DSM-IV-TR criteria) was determined in each diagnostic category by direct observation of SFMD symptoms, psychiatric interviews, SCL 90Rss, collection of previous general practitioners and hospital charts. The frequency of SFMD was considerably higher in DLB (29 patients, 18%) and PD (37 patients, 7.5%) than in any other group (0-2%). The frequency of SFMD in psychiatric patients was 2%. SFMD in PD and DLB were characterised by motor and non-motor patterns and were often accompanied by catatonic signs consisting of posturing stereotypies and negativism (55%). SFMD symptoms preceded PD motor signs by 6 months-5 years in 92% of the 29 DLB and 37 PD patients and in 70% SFMD were recurrent at follow-up. In 93% of these patients, hypochondria was a preceding or concomitant background.

T-cell immune responses against Env from CRF12_BF and subtype B HIV-1 show high clade-specificity that can be overridden by multiclade immunizations.

BACKGROUND: The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections caused by subtype B and BF variants. The aim of this study was to characterize in mice the immunogenic and antigenic properties of the Env protein from CRF12_BF in comparison with clade B, employing prime-boost schemes with the combination of recombinant DNA and vaccinia virus (VV) vectors. METHODOLOGY/PRINCIPAL FINDINGS: As determined by ELISPOT from splenocytes of animals immunized with either EnvBF or EnvB antigens, the majority of the cellular responses to Env were found to be clade-specific. A detailed peptide mapping of the responses reveal that when there is cross-reactivity, there are no amino acid changes in the peptide sequence or were minimal and located at the peptide ends. In those cases, analysis of T cell polifunctionality and affinity indicated no differences with respect to the cellular responses found against the original homologous sequence. Significantly, application of a mixed immunization combining both clades (B and BF) induced a broader cellular response, in which the majority of the peptides targeted after the single clade vaccinations generated a positive response. In this group we could also find significant cellular and humoral responses against the whole gp120 protein from subtype B. CONCLUSIONS/SIGNIFICANCE: This work has characterized for the first time the immunogenic peptides of certain EnvBF regions, involved in T cell responses. It provides evidence that to improve immune responses to HIV there is a need to combine Env antigens from different clades, highlighting the convenience of the inclusion of BF antigens in future vaccines for geographic regions where these HIV variants circulate.

[The importance of early diagnosis for the survival of HIV positive patients]. / La importancia del diagnóstico temprano en la supervivencia de los pacientes HIV positivos.

In Argentina, HIV diagnosis is reached by voluntary testing or symptom-based case findings. However, because of the high proportion of infected individuals unaware of their serologic status new strategies are required. In this article we show how a mathematic model predicts the impact of expanding HIV testing in Argentina. The model is based on time-dependent Markov matrixes and applies parameters-dependent transition-probabilities obtained from both national and international cohort studies. Outputs include time on clinical stages and therapy regime, CD4-count, viral-load, infection-state and age; mortality rates and proportion of unidentified infection at a population-level. Simulations were performed for current testing strategy and for a theoretical scenario with earlier diagnosis. We show how our prediction suggests that diagnosis before onset of symptoms would increase life expectancy by 10.7 years. Also, we show how a reduction of time to diagnosis to 5 or less years from infection would reduce mortality rates in the first year of HAART from 7.6% to 2.1%, the proportion of unrecognized infection from 43.2% to 23.8% and the proportion of individuals with unaware infection needing treatment from 12% to 0.2%. Based on this prediction we stress the importance of implementing health policies aimed at detecting HIV infection in early stages in Argentina.