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We field-assessed the accuracy, acceptability, and feasibility of the SD BIOLINE HIV/Syphilis Duo rapid diagnostic test in three groups: pregnant women, female sex workers (FSW), and men who have sex with men (MSM). Venous blood samples collected in the field were compared with the respective gold standard methods: SD BIOLINE HIV/Syphilis Duo Treponemal Test versus FTA-abs (Wama brand) treponemal laboratory test for syphilis, and SD BIOLINE HIV/Syphilis Duo Test versus the fourth generation Genscreen Ultra HIV Ag-Ag (Bio-Rad brand) laboratory test for HIV. From a total of 529 participants, 397 (75.1%) were pregnant women, 76 (14.3%) FSW and 56 (10.6%) MSM. Sensitivity and specificity parameters of HIV were 100.0% (95% CI: 82.35-100.0%) and 100.0% (95% CI: 99.28-100.0%), respectively. Sensitivity and specificity parameters found for TP antibody detection were 95.00% (95% CI: 87.69-98.62%) and 100.0% (95% CI: 98.18-100.0%), respectively. The SD BIOLINE HIV/Syphilis Duo Test showed high acceptability among participants (85.87%) and health professionals (85.51%), as well as easy usability by professionals (91.06%). The usability of the SD BIOLINE HIV/Syphilis Duo Test kit would not be a barrier to accessing rapid testing, if the product were incorporated into the list of health service supplies.
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INTRODUCTION: The relative efficacy of different antiretroviral (ART) regimens has been extensively evaluated in the context of clinical trials, using HIV viral load (VL) measurements at pre-specified timepoints after ART onset. However, data from real-life studies using combined longitudinal measurements of cumulative viraemia are scarce. This study aimed to address the independent effect of different ART regimens on HIV cumulative viraemia over the first 12 months after treatment initiation, using programmatic data from the Ministry of Health of Brazil. METHODS: Retrospective cohort study analysing cumulative viraemia under the most frequently used ART regimens in Brazil (tenofovir, lamivudine and dolutegravir (regimen 1); tenofovir, lamivudine and efavirenz (regimen 2); tenofovir, lamivudine and ritonavir-boosted atazanavir (regimen 3)). RESULTS AND DISCUSSION: We included 112,243 patients >12 years old who received their first ART prescription between January 2014 and August 2017. Univariate analysis indicated that cumulative viraemia was significantly lower in patients receiving regimen 1 as compared with those receiving regimens 2 or 3 (p<0.0001 for both pairwise comparisons). In a multivariable analysis adjusted for age, sex, baseline T CD4+ counts and baseline HIV VL, ART regimen persisted with statistically significant effect on 12-month cumulative viraemia. The model predicted a 45-unit increase in log10 copy-days/mL cumulative viraemia for regimen 2 as compared with regimen 1, and a 70-unit increase in log10 copy-days/mL cumulative viraemia for regimen 3 as compared with regimen 1 (95%CI 41 to 49 and 61 to 79 respectively; p<0.001 for both comparisons). In models restricted to youths (13 to 24 years old) and female patients, ART regimen had similar effects. ART regimen with dolutegravir in association with a tenofovir-lamivudine backbone was superior to regimens containing efavirenz or boosted atazanavir in reducing HIV VL, as shown by cumulative viraemia over the first 12 months after treatment initiation. The superiority persisted even after adjusting the analysis for potential confounders. CONCLUSIONS: Our findings could bring direct benefits to patients as suggested by lower viral replication during treatment, lower risk of HIV transmission, and a potential reduction in resistance mutations in the initial 12 months under ART.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Adolescente , Adulto , Antirretrovirais/uso terapêutico , Brasil , Contagem de Linfócito CD4 , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Viremia/tratamento farmacológico , Adulto JovemRESUMO
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. The HIV pol genotypic test was performed by genomic sequencing. RESULTS: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. CONCLUSIONS: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Brasil , Farmacorresistência Viral/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
UNLABELLED: Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy. IMPORTANCE: Cholera, a dehydrating diarrheal disease caused by toxigenic strains of the bacterium Vibrio cholerae, emerged in 2010 in Haiti, a country where there were no available records on cholera over the past 100 years. While devastating in terms of morbidity and mortality, the outbreak provided a unique opportunity to study the evolutionary dynamics of V. cholerae and its environmental presence. The present study expands on previous work and provides an in-depth phylodynamic analysis inferred from genome-wide single nucleotide polymorphisms of clinical and environmental strains from dispersed geographic settings in Haiti over a 2-year period. Our results indicate that even during such a short time scale, V. cholerae in Haiti has undergone evolution and diversification driven by positive selection, which may have implications for understanding the global clinical and epidemiological patterns of the disease. Furthermore, the continued presence of the epidemic strain in Haitian aquatic environments has implications for transmission.
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Cólera/epidemiologia , Cólera/microbiologia , Microbiologia Ambiental , Variação Genética , Seleção Genética , Vibrio cholerae O139/classificação , Vibrio cholerae O1/classificação , DNA Bacteriano/química , DNA Bacteriano/genética , Evolução Molecular , Haiti/epidemiologia , Mutação de Sentido Incorreto , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Vibrio cholerae O1/genética , Vibrio cholerae O1/isolamento & purificação , Vibrio cholerae O139/genética , Vibrio cholerae O139/isolamento & purificaçãoRESUMO
Human immunodeficiency virus type 1 (HIV-1) variants show considerable geographical separation across the world, but there is limited information from Central America. We provide the first detailed investigation of the genetic diversity and molecular epidemiology of HIV-1 in six Central American countries. Phylogenetic analysis was performed on 625 HIV-1 pol gene sequences collected between 2002 and 2010 in Honduras, El Salvador, Nicaragua, Costa Rica, Panama, and Belize. Published sequences from neighboring countries (n = 57) and the rest of the world (n = 740) were included as controls. Maximum likelihood methods were used to explore phylogenetic relationships. Bayesian coalescence-based methods were used to time HIV-1 introductions. Nearly all (98.9%) Central American sequences were of subtype B. Phylogenetic analysis revealed that 437 (70%) sequences clustered within five significantly supported monophyletic clades formed essentially by Central American sequences. One clade contained 386 (62%) sequences from all six countries; the other four clades were smaller and more country specific, suggesting discrete subepidemics. The existence of one large well-supported Central American clade provides evidence that a single introduction of HIV-1 subtype B in Central America accounts for most current cases. An introduction during the early phase of the HIV-1 pandemic may explain its epidemiological success. Moreover, the smaller clades suggest a subsequent regional spread related to specific transmission networks within each country.
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Evolução Molecular , Variação Genética , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , Filogenia , Sequência de Bases , Teorema de Bayes , América Central/epidemiologia , Infecções por HIV/transmissão , HIV-1/classificação , Humanos , Funções Verossimilhança , Modelos Genéticos , Epidemiologia Molecular , Dados de Sequência Molecular , Prevalência , Alinhamento de Sequência , Análise de Sequência de DNA , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
Human immunodeficiency virus type 1 subtype C (HIV-1C) represents 30-65% of HIV infections in southern Brazil, and isolated cases of HIV-1C infection have also been reported in Argentina, Uruguay, Paraguay and Venezuela. Phylogenetic studies have suggested that the Brazilian subtype C epidemic was initiated by the introduction of closely related strains. Nevertheless, because of sampling limitations, the point of entry and the timing of subtype C introduction into Brazil, as well as the origin of the founder lineage, remain controversial. The present study investigated the origin, spread and phylogeography of HIV-1C in South America. Phylogenetic analysis showed a well-supported monophyletic clade including all available strains from Brazil, Uruguay and Argentina. Only one lineage from Venezuela was unrelated to the epidemic involving the other three countries. Molecular clock and likelihood mapping analysis showed that HIV-1C introduction in Brazil dated back to the period 1960-1970, much earlier than previously thought, and was followed by a nearly simultaneous star-like outburst of viral lineages, indicating a subsequent rapid spread. Phylogeographic patterns suggested Paraná or Rio Grande do Sul as the possible entrance points of subtype C and an asymmetrical gene flow from Paraná to Sao Paulo, Santa Catarina and Rio Grande do Sul, as well as from Rio Grande do Sul to Sao Paulo fostered by the strong inter-connectivity between population centres in southern Brazil. The study illustrates how coupling phylogeography inference with geographical information system data is critical to understand the origin and dissemination of viral pathogens and potentially predict their future spread.
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Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , Filogeografia/métodos , Epidemias , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , América do Sul/epidemiologiaRESUMO
The biogeographical history of rabies can be reconstructed using molecular data. This work describes the genetic characterization of the Rabies virus variant that circulates in the Desmodus rotundus (vampire bat) population in an epizootic area and is transmitted to herbivorous livestock. The N and G genes of this virus were sequenced, and the phylogenetic trees generated were topologically concordant. Three genetic clusters were identified in the epizootic area and were designated RD1, RD2 and RD3. The results show that the origins of the epizootics in areas RD1 and RD2 were different and that the epizootic in area RD3 was the result of expansion of that in area RD2. The two genes analyzed are conserved, and their identities, which are greater than 98%, were maintained over time and space. The genetic sequences in this study were compared with others retrieved from GenBank, and the high identity of the N and G genes was also shown to be maintained over time and space. The results suggest that the D. rotundus lineages of the Rabies virus from the Atlantic coast of South America are highly conserved.
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Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/virologia , Surtos de Doenças , Vírus da Raiva/classificação , Vírus da Raiva/genética , Raiva/veterinária , Animais , Antígenos Virais/genética , Brasil/epidemiologia , Bovinos , Quirópteros/virologia , Análise por Conglomerados , Sequência Conservada , Glicoproteínas/genética , Dados de Sequência Molecular , Proteínas do Nucleocapsídeo/genética , Filogenia , Polimorfismo Genético , Raiva/epidemiologia , Vírus da Raiva/isolamento & purificação , Análise de Sequência de DNA , Proteínas do Envelope Viral/genéticaRESUMO
Thirty-eight samples of Rabies Virus isolated from dogs and crab-eating foxes (Cerdocyon thous) in Northeastern Brazil were characterized genetically by analyzing the G gene and the psi region. The results show that there are two groups of Rabies Virus lineages circulating among domestic and wild animals in the region. The topologies of the phylogenetic trees of the G gene and psi region are similar and reveal the existence of geographic groups. The genetic diversity of the lineages isolated from wild animals (wild group) was approximately twice that of the lineages isolated from domestic animals (domestic group), and the genetic distance between the two groups was 9.93%. Polymorphism analysis revealed specific intra- and inter-group molecular signatures for both the G gene and psi region. Together with the analysis of the N gene undertaken previously, the results of this study confirm the existence of a Rabies Virus phylogroup in Northeastern Brazil (NB) circulating in the C. thous population, making this species a rabies biotype in the region.
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Doenças do Cão/virologia , Raposas/virologia , Vírus da Raiva/genética , Vírus da Raiva/isolamento & purificação , Raiva/veterinária , Animais , Antígenos Virais/genética , Encéfalo/patologia , Encéfalo/virologia , Brasil/epidemiologia , Reservatórios de Doenças/virologia , Doenças do Cão/epidemiologia , Cães , Glicoproteínas/genética , Dados de Sequência Molecular , Proteínas do Nucleocapsídeo/genética , Filogenia , Raiva/epidemiologia , Raiva/virologia , Vírus da Raiva/classificação , Proteínas do Envelope Viral/genéticaRESUMO
HPV-18 is the second most prevalent human papillomavirus genotype found in cervical cancer. Nucleotide variations in HPV-18 sequence can interfere with the viral oncogenic potential. However, the knowledge about HPV-18 variants in Brazil is still limited. The present study aims to determine the LCR, E6, and L1 genetic variability of HPV-18 variants found in women co-infected with HIV-1 in Central Brazil. Four HPV-18 samples were identified and had the LCR, E6, and L1 genomic regions sequenced. It was possible to characterize three European variants and one African variant of HPV-18. All of them are new variants, showing nucleotide substitutions not previously reported. Nucleotide variations in binding sites for transcriptional factors were observed. Phylogenetic analysis was also performed, evidencing the three clusters related to the Asian-American, African, and European variants. The characterization of HPV genetic variability is of pivotal importance to the understanding of the viral pathogenicity.
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Variação Genética , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/isolamento & purificação , Neoplasias do Colo do Útero/virologia , Sequência de Bases , Brasil , Feminino , Papillomavirus Humano 18/classificação , Humanos , Dados de Sequência Molecular , Filogenia , Proteínas Virais/genéticaRESUMO
This study analyzed the genes pol and env to determine the genetic variability of HIV-1 in Central Brazil. Forty-one isolates of HIV-1-infected individuals had protease, reverse transcriptase, and C2C3/ env amplified by nested PCR and sequenced. The subtype was determined by the program REGA and phylogenetic analyses. The samples identified as putative recombinant forms were analyzed by SimPlot. A high prevalence of subtype B (95.1%) was observed, followed by mosaic viruses B/F (4.9%). The amino acid sequences from 30 HIV-1 isolates were analyzed for the antigenic intrasubtype diversity. The most prevalent gp120 V3 loop motif was the GPGR (United States/Europe) (43.3%), described in B and F subtypes, followed by the GPGK tetrapeptide (10%). The Brazilian variant B" (GWGR), GFGR, and GLGR tetrapeptides were found in 6.7%. Other V3 variants were found in eight isolates (26.7%). Phylogenetic tree analysis was also performed in order to verify the relationship of the HIV-1 samples from Central Brazil with other HIV-1 sequences that circulate in Brazil. The subtype B sequences from Central Brazil formed a polyphyletic cluster in the tree, indicating that these strains are similar to those from other geographic regions. These results contribute to the understanding of HIV in Brazil, and may prove useful for the development of vaccine candidates.