Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Killer immunoglobulin-like receptor (KIR) genes are associated with the risk of episodes of high-level and detectable viremia among HIV controllers

Different levels of viremia control are observed among HIV-1-infected individuals. Approximately 1% of the HIV-1-seropositive population suppresses viral replication to extremely low or undetectable levels in the absence of antiretroviral therapy and are termed HIV controllers (HICs) or elite controllers (ECs). In this study, we analyzed the distribution of HLA-B and -C, KIR, CCR5 genes, as well as selected SNPs to investigate their impact on the viral control observed in a cohort of Brazilian HICs

Distribution of CCR5 genotypes and HLA Class I B alleles in HIV-1 infected and uninfected injecting drug users from Rio de Janeiro, Brazil

Submitted by Frederico Azevedo ([email protected]) on 2010-11-04T18:27:54Z No. of bitstreams: 1 distribution_of_ccr5.pdf: 128024 bytes, checksum: 496439e13f1d836aee797a30ceb293f3 (MD5)Made available in DSpace on 2010-11-04T18:27:54Z (GMT). No. of bitstreams: 1 distribution_of_ccr5.pdf: 128024 bytes, checksum: 496439e13f1d836aee797a30ceb293f3 (MD5) Previous issue date: 2009Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation - FIOCRUZDepartment of Health Information, Institute of Scientific and Technologic Information and Communication in Health, Oswaldo Cruz Foundation - FIOCRUZDepartment of Health Information, Institute of Scientific and Technologic Information and Communication in Health, Oswaldo Cruz Foundation - FIOCRUZLaboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation - FIOCRUZHost genetic factors play an important role in the HIV epidemic dynamics, and have been considered in studies assessing susceptibility/resistance to HIV-1 infection as well as clinical evolution. Class I and Class II HLA alleles have been associated with the heterogeneity of HIV-1 infection susceptibility, as protective or risk factors for HIV-1 transmission. Moreover, a 32-base pair deletion in the HIV-1 CCR5 gene-coding region confers resistance to HIV-1 infection in homozygous individuals for the deleted allele. In this study, DNA samples from HIV-1 infected and uninfected injecting drug users (IDUs) from Rio de Janeiro were PCR amplified to determine CCR5 genotypes based on the presence of the CCR5D32 mutation and typed for the HLA-B locus, in an attempt to assess possible associations between these genetic factors and susceptibility/resistance to HIV-1 infection. The distribution of CCR5 genotypes between the two IDU groups did not differ. The homozygous mutant genotype D32/D32 was not found in this study. Except for HLA-B*45 (4.0% vs. 3.0%; p = 0.04) and for B*51 (12.1% vs. 4.4%; p = 0.002), no statistically significant differences were made evident when analyzing the frequencies of each HLA-B allele between Caucasian and non-Caucasian IDUs. The most frequent HLA-B alleles were B*15; B*35; B*44 and B*51. Although some differences in the allele frequencies could be observed between the two IDU groups, none of these was statistically significant. Therefore, no putative association between these geneticmarkers and susceptibility/resistance to HIV-1 infection could be made evident in the present study. So far, the assessment of genetic markers among the IDU population has been restricted to North American, European, and Asian studies and this report represents a pioneer descriptive study of the distribution of CCR5 genotypes and HLA-B alleles in Rio de Janeiro, Brazi

Trends in drug resistance mutations in antiretroviral-naïve intravenous drug users of Rio de Janeiro

Made available in DSpace on 2010-08-23T16:58:31Z (GMT). No. of bitstreams: 3 Bastos_Trends in drug resistance.pdf: 3272974 bytes, checksum: 095f6e6a6933b4895bf4b00a2cdc33e2 (MD5) license.txt: 1842 bytes, checksum: 47f2ac55c8587044ece12a43162ff1ab (MD5) Bastos_Trends in drug resistance.pdf.txt: 6 bytes, checksum: 6d93d3216dc4a7f5df47d4876fbec4d3 (MD5) Previous issue date: 2006Made available in DSpace on 2010-11-04T14:20:00Z (GMT). No. of bitstreams: 3 Bastos_Trends in drug resistance.pdf.txt: 6 bytes, checksum: 6d93d3216dc4a7f5df47d4876fbec4d3 (MD5) license.txt: 1842 bytes, checksum: 47f2ac55c8587044ece12a43162ff1ab (MD5) Bastos_Trends in drug resistance.pdf: 3272974 bytes, checksum: 095f6e6a6933b4895bf4b00a2cdc33e2 (MD5) Previous issue date: 2006Department of Immunology Laboratory of AIDS and Molecular Immunology Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, BrazilDepartment of Health Information, Center for Information on Science and Technology, FIOCRUZ, Rio de Janeiro, BrazilDepartment of Health Information, Center for Information on Science and Technology, FIOCRUZ, Rio de Janeiro, BrazilDepartment of Immunology Laboratory of AIDS and Molecular Immunology Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, BrazilDepartment of Immunology Laboratory of AIDS and Molecular Immunology Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, BrazilDepartment of Immunology Laboratory of AIDS and Molecular Immunology Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, BrazilDNA sequencing of a pol gene fragment from drug-naive injecting drug users samples obtained at two time points of the Brazilian AIDS epidemic(Pre-HAARTera: 1994 to early 1997, n = 27; post-HAARTera: 1999-2001, n = 38) was undertaken to assess HIV-1 antiretroviral drug resistance mutations and subtyping profiles. Genotypic analysis revealed the presence of PR primary L90M, D30N, M461, and V82A mutations in 7.9% of the post- HAARTgroup, and a high frequency of secondary mutations (84.2%). Nucleoside RT-associated mutations were observed in 13.2%. In the pre- HAARTgroup, a higher frequency of RT mutations was observed (22.2%) and no PR primary mutations were found, in agreement with the introduction of protease inhibitors (Pis) in therapy du ring the same period. The identification of7 .9% of drug-naive injecting drug users already bearing RT/PR primary resistance mutations in the post- HAARTera group constitutes a major concern in terms of dissemination of drug resistant viruses. The resistance mutations profile ofthe individuals may reflect the context of antiretroviral treatment in Brazil at the sample collection periods (1994- 1997 and 1999-2001). In spite of the differences observed in the drug resistance profiles, similar frequencies of subtype B (63.0 vs. 73.7%), F (22.2 vs. 10.5%), and recombinant B/F (14.8 vs. 15.8%) viruses were found, respectively, in the pre- and post-HAART groups

Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control

Abstract Background Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n = 5) and (2) elite controllers (ECs; n = 6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and flanking CTL epitopes. Results Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were < 1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (< 1%); all VCs showed a high number of mutations, with significant frequency changes between VE and VL visits. A higher frequency of internal mutations was observed for gag epitopes, with significant changes across visits compared to Nef epitopes, indicating a pattern associated with differential genetic pressure. Conclusions The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants

<i>Env</i> ML tree (6922–7277 relative to HXB2) from Brazilian RDS drug users clusters and reference sequences with highest similarity score to each group selected by HIV BLAST, as well as, Brazilian sequences with assigned transmission category [heterosexual (HET), homosexual (HSH), blood donor (BD) or vertical transmission (VT)] belonging to subtypes B, C and F1.

<p>The <i>aLRT</i> support values superior to 0.90 are indicated. Horizontal branch lengths are drawn to scale with the bar at the bottom indicating nucleotide substitutions per site.</p

Schematic representation of responded driven sampling (RDS) recruitment network from Itajaí (SC), Recife (PE), Salvador (BA) e Rio de Janeiro (RJ), places were the phylogenetic cluster were detected.

<p>Large circles represent the first recruited individual in each network, designated as seeds and small circles represent the consecutive waves of recruitment. HIV-1 positive individuals were colored in red, HIV-1 negative individuals in blue and individuals not tested for HIV in gray. The numbers were depicted only in HIV-1 positive individuals and were related to the sequence numbers (e.g. individual marked as number 1 in Itajai RDS representation corresponds to the RDSSC001 sequence).</p

Map of Brazil showing the frequency of HIV-1 genetic variants across the nine studied cities/State [Recife (PE), Salvador (BA)—Northeast region], [Rio de Janeiro (RJ), Belo Horizonte (MG)—Southeast region], [Itajaí (SC), Curitiba (PR)—South Region], [Campo Grande (MS), Brasilia (DF)—Center West region].

<p>The number of <i>env</i> and <i>pol</i> analyzed samples was depicted in each graphic.</p

List and frequency of drug resistance mutations detected in each studied city stratified by drug class.

<p>DRM: Drug resistance mutations; NRTI: Nucleoside/Nucleotide Reverse Transcriptase Inhibitors; NNRTI: Non-nucleoside reverse-transcriptase inhibitors; PI: Protease inhibitors</p><p>List and frequency of drug resistance mutations detected in each studied city stratified by drug class.</p

The role of ‘‘long-term’’ and ‘‘new’’ injectors in a declining HIV/AIDS epidemic in Rio de Janeiro, Brazil

MARIANA A. HACKER,1 SAMUEL R. FRIEDMAN,2 PAULO ROBERTO TELLES,3 SYLVIA LOPES TEIXEIRA,4 VERA BONGERTZ,4 MARIZA G. MORGADO,4 AND FRANCISCO INÁCIO BASTOS1 - 1Department of Health Information, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil - 2National Development Research Institutes, Inc., New York City, New York, USA - 3Rio de Janeiro Harm Reduction Project, State University of Rio de Janeiro, Rio de Janeiro, Brazil - 4Department of Immunology, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilMade available in DSpace on 2010-08-23T16:58:32Z (GMT). No. of bitstreams: 3 license.txt: 1842 bytes, checksum: e9b25f9982fe169d83a2786470bbe0ba (MD5) Bastos_The role_2005.pdf: 290103 bytes, checksum: 41a70ae3327517ebfee5917d9b96b702 (MD5) Bastos_The role_2005.pdf.txt: 70236 bytes, checksum: d1554f4bde58f72c3cad1c1065d1ed4d (MD5) Previous issue date: 2005Made available in DSpace on 2010-11-04T14:20:05Z (GMT). No. of bitstreams: 3 Bastos_The role_2005.pdf.txt: 70236 bytes, checksum: d1554f4bde58f72c3cad1c1065d1ed4d (MD5) Bastos_The role_2005.pdf: 290103 bytes, checksum: 41a70ae3327517ebfee5917d9b96b702 (MD5) license.txt: 1842 bytes, checksum: e9b25f9982fe169d83a2786470bbe0ba (MD5) Previous issue date: 2005The project in its different phases and components was funded by the Oswaldo Cruz Foundation/Brazilian Ministry of Health, the Rio de Janeiro State Research Council (FAPERJ) and the National Research Council (CNPq), and the World Health Organization (WHO). SRF was supported by the US National Institute on Drug Abuse grants R01 DA03574 (Risk Factors for AIDS Among Intravenous Drug Users) and R01 DA13128 (Networks, Norms and HIV Risk Among Youth).Oswaldo Cruz Foundation. Department of Health Information. Rio de Janeiro, RJ, Brazil.National Development Research Institutes, Inc., New York City, New York, USAState University of Rio de Janeiro. Rio de Janeiro Harm Reduction Project. Rio de Janeiro, RJ, Brazil.Department of Immunology, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilDepartment of Immunology, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilDepartment of Immunology, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilOswaldo Cruz Foundation. Department of Health Information. Rio de Janeiro, RJ, Brazil.Background. A substantial decline of HIV prevalence has been observed in injection drug users (IDUs) from Rio de Janeiro, in recent years. Differential characteristics and behaviors of new (injecting for ¼6 y) injectors may help to understand recent changes and to implement appropriate prevention strategies. recruited from different communities, interviewed, and tested for HIV. Contingency table analysis and t-tests were used to assess differences between new and long-term injectors. Multiple logistic regression was used to identify independent predictors of HIV serostatus for long-term and new injectors. Results. HIV prevalence was 11.7% for 309 long-term injectors (95% CI 8.1– 15.3) and 4.3% for 300 new injectors (95% CI 2.0–6.6). New injectors reported having engaged in treatment and having received syringes from needle exchange programs (NEPs) more frequently than long-term injectors in the last 6 months, but sharing behaviors remained frequent and even increased vis-a`-vis long-term injectors. For male new injectors, ‘‘sexual intercourse with another man’’ was found to be the sole significant risk factor for HIV infection (Adj OR¼8.03; 95% CI 1.52–42.48). Among male long-term injectors, ‘‘to have ever injected with anyone infected with HIV’’ (Adj OR¼3.91; 95% CI 1.09–14.06) and to have ‘‘ever been in prison’’ (Adj OR¼2.56; 95% CI 1.05–6.24) were found to be significantly associated with HIV infection. Discussion. New injectors are seeking help in drug treatment centers or needle exchange programs. They differ from long-term injectors in terms of their risk factors for HIV infection and have lower prevalence levels for HIV. Such differences may help to understand the recent dynamics of HIV/AIDS in this population and highlight the need to reinforce new injectors’ help-seeking behavior and to reduce current unacceptably high levels of unprotected sex and syringe sharing in new injectors despite attendance of prevention/treatment programs