Publications by authors named "Jose C Couto-Fernandez"

The human immunodeficiency virus type 1 (HIV-1) can be transmitted via parenteral, sexual, or vertical exposure routes. The number of HIV-1 cases detected yearly in children and adolescents in Brazil did not decrease over the last decade, representing ~5% of total cases described in the country. In recent years, the HIV-1 diversity and the prevalence of transmitted drug resistance mutations (TDRM) are moving toward a marked increase.

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Article Synopsis
  • Monitoring genetic diversity and drug resistance mutations (DRMs) in HIV-1 is essential for understanding its epidemiology, particularly in a study of 42 HIV-positive pregnant women in Luanda, who had not yet begun antiretroviral therapy (ART).
  • The research revealed a variety of HIV-1 subtypes, with subtype C being the most prevalent at 38%, and identified that 18% of the analyzed sequences contained DRMs, largely affecting non-nucleoside reverse transcriptase inhibitors.
  • The findings highlight the importance of continuing to monitor HIV diversity and resistance to inform and potentially revise existing ART guidelines in Angola based on current data.
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Background: Increasing genetic diversity of HIV-1 and emergence of drug-resistant mutations may reduce the efficacy of antiretroviral therapy and prophylaxis that are used to prevent mother-to-child transmission. The aim of this study was to assess the genetic diversity and prevalence of drug-resistant mutations among HIV-infected pregnant women.

Design And Setting: Cross-sectional study at an outpatient clinic for infectious diseases within gynecology and obstetrics.

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Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015.

Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions.

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The Northeastern Brazilian region has experienced a constant increase in the number of newly reported AIDS cases over the last decade, but the genetic diversity of HIV-1 strains currently disseminated in this region remains poorly explored. HIV-1 pol sequences were obtained from 140 patients followed at outpatient clinics from four Northeastern Brazilian states (Alagoas, Bahia, Ceará, and Piauí) between 2014 and 2015. Subtype B was the most prevalent HIV-1 clade (72%) detected in the Northeastern region, followed by subtypes F1 (6%), C (5%), and D (1%).

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Adverse reactions are the main cause of treatment discontinuation among HIV+ individuals. Genes related to drug absorption, distribution, metabolism and excretion (ADME) influence drug bioavailability and treatment response. We have investigated the association between single nucleotide polymorphisms (SNPs) in 29 ADME genes and intolerance to therapy in a case-control study including 764 individuals.

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Antiretroviral (ARV) resistance mutations in human immunodeficiency virus type 1 (HIV-1) infection may reduce the efficacy of prophylactic therapy to prevent mother-to-child transmission (PMTCT) and future treatment options. This study evaluated the diversity and the prevalence of transmitted drug resistance (TDR) in protease (PR) and reverse transcriptase (RT) regions of HIV-1 pol gene among 87 ARV-naive HIV-1-infected pregnant women from Rio de Janeiro, Brazil, between 2012 and 2015. The viral diversity comprised HIV-1 subtypes B (67.

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The HIV-1 epidemiology has changed over the past decade toward a marked increase in the circulation of strains previously restricted to local epidemics. Recent molecular epidemiological surveys identified some HIV-1 strains of probable African origin circulating in Brazil, including the Circulating Recombinant Form (CRF) 45_cpx, a complex A1/K/U recombinant that circulates in Central Africa. Here, we characterize partial genomic sequences and reconstruct the evolutionary history of HIV-1 CRF45_cpx-related recombinant samples identified in independent studies carried out with HIV+ individuals in Brazil.

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The HIV-1 epidemic in Brazil is driven by subtypes B, F1, and C and recombinants forms among those subtypes. The distribution of HIV-1 subtypes, however, may vary across different Brazilian regions and the molecular epidemiologic profile in Northern Brazil remains poorly explored. HIV-1 pol sequences were obtained from 305 patients failing antiretroviral therapy followed at outpatient clinics from five Northern Brazilian states.

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HIV-1 CRF02_AG is responsible for at least 8% of the HIV-1 infections worldwide and is distributed mainly in West Africa. CRF02_AG has recently been reported in countries where it is not native, including Brazil. In a previous study including 10 CRF02_AG Brazilian samples, we found at least four independent introductions and two autochthonous transmission networks of this clade in Brazil.

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Previous studies indicate that the HIV-1 subtype C epidemic in southern Brazil was initiated by the introduction of a single founder strain probably originating from east Africa. However, the exact country of origin of such a founder strain as well as the origin of the subtype C viruses detected outside the Brazilian southern region remains unknown. HIV-1 subtype C pol sequences isolated in the southern, southeastern and central-western Brazilian regions (n = 209) were compared with a large number (n ~ 2,000) of subtype C pol sequences of African origin.

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The HIV-1 subtype C has spread efficiently in the southern states of Brazil (Rio Grande do Sul, Santa Catarina and Paraná). Phylogeographic studies indicate that the subtype C epidemic in southern Brazil was initiated by the introduction of a single founder virus population at some time point between 1960 and 1980, but little is known about the spatial dynamics of viral spread. A total of 135 Brazilian HIV-1 subtype C pol sequences collected from 1992 to 2009 at the three southern state capitals (Porto Alegre, Florianópolis and Curitiba) were analyzed.

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HIV-1 CRF02_AG is the most prevalent intersubtype recombinant form worldwide. Six HIV-1 samples from patients living in Rio de Janeiro, Brazil, were subtyped as CRF02_AG at the pol gene between 2004 and 2011. To trace the origin of these viruses, they were compared with 793 CRF02_AG pol sequences of African origin and another four Brazilian CRF02_AG pol sequences previously described.

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Objective: To evaluate the polymorphisms and resistance mutations in gp41 HR1 region of HIV-1.

Methods: The study included 28 HIV-positive patients undergoing enfuvirtide (ENF) treatment or not from Porto Alegre, Rio Grande do Sul state, and Rio de Janeiro, Rio de Janeiro state, between 2006 and 2009. Resistance mutations and polymorphisms of the gp41 HR1 region were detected using the genomic DNA of 12 ENF-untreated patients and 16 patients in ENF treatment, encompassing subtypes B, C, and F1.

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Due to the co-circulation of HIV-1 subtypes B and F1 in Brazil, a large variety of unique BF1 recombinant forms (URFs_BF1) and four circulating BF1 recombinant forms (CRF28, CRF29, CRF39 and CRF40) have been described. The aim of this study was to investigate mosaic structure and phylogenetic relationship among several BF1 (protease-reverse transcriptase, pr/rt) recombinant sequences obtained from a group of patients from Rio de Janeiro, Brazil, from 1994 to 2005. Phylogenetic relationships were estimated by Bayesian and SplitsTree methods.

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Concerns have been raised that universal availability of antiretroviral agents in resource-limited settings might lead to the emergence and spread of resistant strains. We present the largest survey on human immunodeficiency virus type 1 (HIV-1) resistance among treatment-naïve and experienced patients followed in small, relatively underprivileged cities in Brazil with universal availability to standard of care antiretroviral combinations. Samples were collected between 2004 and 2006 from 95 patients followed in the cities of Saquarema and Santo Antonio de Pádua, state of Rio de Janeiro.

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Highly active antiretroviral treatment (HAART) of human immunodeficiency type 1 (HIV-1) infection is very effective in controlling infection, but elimination of viral infection has not been achieved as yet, and upon treatment interruption an immediate rebound of viremia is observed. A combination of HAART with an immune stimulation might allow treatment interruption without this rebounding viremia, as the very low viremias observed with successful HAART may be insufficient to permit maintenance of a specific anti-HIV-1 immune response. The objective of this study was to compare the humoral immune response of individuals undergoing successful HAART (NF=no failure) with that of individuals with evidence of failure of therapy (FT) and to verify if the viremia peaks observed in individuals with therapy failure would act as a specific stimulus for the humoral anti-HIV-1 immune response.

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It has been postulated that the non-synonymous divergence (distance to the subtype consensus sequence) observed in several HIV-1 subtype populations during 1990s attained the maximum limit that is compatible with viral fitness or survival, at least in the V3 env gene domain. To test this hypothesis, 145 subtype B and 64 subtype F env V3 sequences isolated from Brazilian HIV-1 positive patients between 1989 and 2004 were analyzed. HIV-1 env V3 sequences were grouped by year of collection and the mean intra-subtype diversity and divergence were examined at synonymous, non-synonymous, and amino acid level.

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In the State of Rio de Janeiro, Brazil, HIV-1 diversity surveys have been performed mainly in the capital, and little is known about HIV-1 molecular epidemiology in small, inner cities. We studied 87 polymerase sequences recovered from 2 different studies conducted in inner cities of Rio de Janeiro State: a cross-sectional survey of patients receiving care in the small city of Santo Antonio de Pádua, and a case series of patients who were failing HAART in 26 additional inner cities throughout the State. Subtypes B (83.

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Genetic variability of human immunodeficiency virus type-1(HIV-1) is a potential threat for both diagnosis and treatment of HIV/AIDS, as well as the development of effective vaccines. Up to now, HIV subtypes circulating among HIV-positive patients in the state of Espírito Santo were not known. In the present study, blood samples from 100 therapy-naïve HIV-1 infected patients were collected and the HIV subtype was determined through the Heteroduplex Mobility Assay (HMA).

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The reconstruction of the epidemic history of several HIV populations, by using methods that infer the population history from sampled gene sequence data, has revealed important subtype-specific and regional-specific differences in patterns of epidemic growth. Here, we employ Bayesian coalescent-based methods to compare the population history of the HIV-1 subtype B and F1 epidemics in Brazil from non-contemporary env and pol gene sequences. Our results suggest that after the introduction of the subtypes B and F1 into Brazilian population, around mid to late 1960s and late 1970s, respectively, these subtypes experienced an initial period of exponential growth with similar epidemic growth rates ( approximately 0.

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HIV-1 Subtype D occurs mainly in East and Central African countries, especially Uganda, where the prevalence of HIV-1 infection is among the highest in the world. We present the phylogenetic analysis of one nonautochthonous and four autochthonous (including a near full-length genome) Brazilian HIV-1 subtype D strains identified in Rio de Janeiro State, where subtypes B, F1, and BF1 recombinants predominate. Phylogenetic inferences using maximum likelihood were applied on a near-full length genome and on concatenated gag, protease, reverse transcriptase, integrase, C2V3/env, gp41, and nef segments.

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