Increased IL-8 levels in HIV-infected individuals who initiated ART with CD4 T cell counts <350 cells/mm - A potential hallmark of chronic inflammation.

The identification of inflammatory markers in HIV+ individuals on ART is fundamental since chronic ART-controlled HIV infection is linked to an increased inflammatory state. In this context, we assessed plasma levels of pro-inflammatory cytokines (IL-1β, IL-8, and IL-12p70) of HIV+ individuals who initiated ART after immunosuppression (CD4 T cell counts <350 cells/mm). HIV+ individuals were stratified according to two extreme phenotypes: Slow Progressors (SPs; individuals with at least 8 years of infection before ART initiation) and Rapid Progressors (RPs; individuals who needed to initiate ART within 1-4 years after infection).

High CXCL10/IP-10 levels are a hallmark in the clinical evolution of the HIV infection.

The aim of this study was to investigate the modulation of plasma CXCL10, CCL20, CCL22, CCL2, CCL17 and CCL24 levels in HIV-positive patients grouped according to extreme phenotypes of progression to AIDS, and at different stages of HIV infection. HIV-positive individuals with extreme phenotypes of AIDS progression (n=58) at different clinical stages (chronic individuals, both pre-HAART and under-HAART) and HIV-negative controls (n=20) were evaluated. Additionally, HIV-positive individuals that initiated HAART with >350CD4T-cells/mm were compared with those who initiated treatment with <350CD4T-cells/mm.

Novel genetic associations and gene-gene interactions of chemokine receptor and chemokine genetic polymorphisms in HIV/AIDS.

Objective: To investigate the influence of candidate polymorphisms on chemokine receptor/ligand genes on HIV infection and AIDS progression (HIV/AIDS).

Design: Fifteen polymorphisms of the CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCR6, CCL20, CCL22 and CXCL10 genes were analysed in 206 HIV-positive patients classified as rapid progressors (n = 40), or nonrapid progressors (n = 166), and in 294 HIV-seronegative patients.

Methods: The polymorphisms were genotyped using minisequencing.

Endosomal toll-like receptor gene polymorphisms and susceptibility to HIV and HCV co-infection - Differential influence in individuals with distinct ethnic background.

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV-), taking into account their ethnic background.

Short-Term Dynamic and Local Epidemiological Trends in the South American HIV-1B Epidemic.

The human displacement and sexual behavior are the main factors driving the HIV-1 pandemic to the current profile. The intrinsic structure of the HIV transmission among different individuals has valuable importance for the understanding of the epidemic and for the public health response. The aim of this study was to characterize the HIV-1 subtype B (HIV-1B) epidemic in South America through the identification of transmission links and infer trends about geographical patterns and median time of transmission between individuals.

Role of SEP15 Gene Polymorphisms in the Time of Progression to AIDS.

Aims: HIV infection is a chronic disease that requires intensive treatment in its later phases, including dietary supplementation. Several studies have suggested clinical improvements in patients with high levels of selenium, linking these levels with a longer progression to AIDS. The objective of this study was to verify the association of two polymorphisms in the SEP15 gene, which encodes a selenoprotein that is responsible for the transport of selenium in cells, with the time of progression to AIDS in HIV-1-infected patients.

Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection.

Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93-136.5 months for SPs and 7.

New Insights about Treg and Th17 Cells in HIV Infection and Disease Progression.

Treg and Th17 cell subsets are characterized by the expression of specific transcriptional factors and chemokine receptor as well as by secretion of specific cytokine and chemokines. These subsets are important to the differentiation, expansion, homing capacity, and recruitment of several different immune cell populations to the site of infection. Whereas Treg cells maintain self-tolerance and control the activation and expansion of autoreactive CD4(+) T effector cells through an anti-inflammatory response, Th17 cells, in an exacerbated unregulated proinflammatory response, can promote autoimmunity.

Contribution of Epidemiological Predictors in Unraveling the Phylogeographic History of HIV-1 Subtype C in Brazil.

Unlabelled: The phylogeographic history of the Brazilian HIV-1 subtype C (HIV-1C) epidemic is still unclear. Previous studies have mainly focused on the capital cities of Brazilian federal states, and the fact that HIV-1C infections increase at a higher rate than subtype B infections in Brazil calls for a better understanding of the process of spatial spread. A comprehensive sequence data set sampled across 22 Brazilian locations was assembled and analyzed.

Analysis of single-nucleotide polymorphisms in the APOBEC3H gene of domestic cats (Felis catus) and their association with the susceptibility to feline immunodeficiency virus and feline leukemia virus infections.

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are widely distributed retroviruses that infect domestic cats (Felis catus). Restriction factors are proteins that have the ability to hamper retroviruses' replication and are part of the conserved mechanisms of anti-viral immunity of mammals. The APOBEC3 protein family is the most studied class of restriction factors; they are cytidine deaminases that generate hypermutations in provirus DNA during reverse transcription, thus causing hypermutations in the viral genome, hindering virus replication.

New insights into the in silico prediction of HIV protease resistance to nelfinavir.

The Human Immunodeficiency Virus type 1 protease enzyme (HIV-1 PR) is one of the most important targets of antiretroviral therapy used in the treatment of AIDS patients. The success of protease-inhibitors (PIs), however, is often limited by the emergence of protease mutations that can confer resistance to a specific drug, or even to multiple PIs. In the present study, we used bioinformatics tools to evaluate the impact of the unusual mutations D30V and V32E over the dynamics of the PR-Nelfinavir complex, considering that codons involved in these mutations were previously related to major drug resistance to Nelfinavir.

Temporal dynamics of HIV-1 circulating subtypes in distinct exposure categories in southern Brazil.

Background: The HIV-1 epidemic in Brazil is predominantly driven by subtype B. However, in Brazilian Southern region subtype C prevails and a relatively high AIDS incidence rate is observed. The aim of the present study was to assess the temporal dynamics of HIV-1 subtypes circulating in patients from distinct exposure categories in Southern Brazil.

Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC.

Background: Entry inhibitors are a class of antiretroviral (ARV) drugs that prevent HIV replication by blocking viral entry into the host cell. The investigation of naturally occurring mutations associated with entry inhibitors across subtypes is required because genetic differences between HIV-1 variants may influence the emergence of drug resistance. Despite the importance of subtype C, which predominates globally, the majority of studies include only subtype B strains.

Reviewing the history of HIV-1: spread of subtype B in the Americas.

The dispersal of HIV-1 subtype B (HIV-1B) is a reflection of the movement of human populations in response to social, political, and geographical issues. The initial dissemination of HIV-1B outside Africa seems to have included the passive involvement of human populations from the Caribbean in spreading the virus to the United States. However, the exact pathways taken during the establishment of the pandemic in the Americas remain unclear.

Co-circulation HIV-1 subtypes B, C, and CRF31_BC in a drug-naïve population from Southernmost Brazil: analysis of primary resistance mutations.

In Southernmost Brazil HIV-1 subtypes B, C, and CRF31_BC co-circulates and, since 1996 with the implementation of free access to highly active antiretroviral treatment (HAART), this epidemic is under a quite characteristic selective pressure. The profile of mutations and polymorphisms in the protease (PR) and reverse transcriptase (RT) genes of HIV-1 from untreated patients living in Porto Alegre, Southernmost Brazil were evaluated in order to identify the subtypes and circulating drug resistant genotypes. Blood samples from 99 HIV-1 positive drugs-naïve patients were collected from 2006 to 2007 in Porto Alegre, Brazil.