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BACKGROUND: The World Health Organization (WHO) recommends that HIV treatment scale-up is accompanied by a robust assessment of drug resistance emergence and transmission. The WHO HIV Drug Resistance (HIVDR) monitoring and surveillance strategy includes HIVDR testing in adults both initiating and receiving antiretroviral therapy (ART). Due to limited information about HIVDR in Mozambique, we conducted two nationally representative surveys of adults initiating and receiving first-line ART regimes to better inform the HIV program. METHODS: We carried out a cross-sectional study between March 2017 and December 2019. Adults (older than 15 years) living with HIV (PLHIV) initiating ART or receiving first-line ART for between 9-15 months at 25 health facilities across all eleven provinces in Mozambique were included. Genotypic HIVDR was assessed on dried blood spots (DBS) when viral loads were ≥ 1000 copies/ml. Genotypic resistance for non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was determined using the Stanford HIV database algorithm 9.5 and calibrated population resistance tool 8.1. RESULTS: Of 828 participants -enrolled, viral load (VL) testing was performed on 408 initiators and 409 ART experienced. Unsuppressed VL was found in 68.1% 419 initiators and 18.8% (77/409) of the ART experienced. Of the 278 initiators and 70 ART experienced who underwent sequencing, 51.7% (144/278) and 75.7% (53/70) were sequenced successfully. Among the new initiators, pretreatment drug resistance (PDR) for NNRTI and PI was found in 16.0% (23/144) and 1.4% (2/144) of the participants, respectively. Acquired drug resistance (ADR) was found in 56.5% (30/53) of the ART-experienced participants of whom 24.5% (13/53) were resistant to both NRTI and NNRTI. CONCLUSION: High rates of PDR and ADR for NNRTI and ADR for NRTI were observed in our study. These findings support the replacement of NNRTIs with dolutegravir (DTG) but high levels of NRTI resistance in highly treatment-experienced individuals still require attention when transitioning to new regimens. Moreover, the study underlines the need for routine VL testing and HIVDR surveillance to improve treatment management strategies.
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Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piridonas , Tenofovir , Humanos , Moçambique/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Masculino , Farmacorresistência Viral/genética , Feminino , Adulto , Estudos Transversais , HIV-1/efeitos dos fármacos , HIV-1/genética , Fármacos Anti-HIV/uso terapêutico , Piridonas/uso terapêutico , Pessoa de Meia-Idade , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Oxazinas/uso terapêutico , Adulto Jovem , Piperazinas/uso terapêutico , Adolescente , Carga Viral/efeitos dos fármacos , GenótipoRESUMO
In the original publication [...].
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Understanding spatial configuration of sexual network structure is critical for effective use of HIV preventative interventions in a community. However, this has never been described at the population level for any setting in sub-Saharan Africa. We constructed the comprehensive geospatial sexual network among new heterosexual partnerships in rural KwaZulu-Natal, South Africa. In the Africa Health Research Institute (AHRI)'s population-based surveillance, we identified stable sexual partnerships among individuals (≥15 years) from 2003 to 2016. Sexual partnerships and residency were recorded via household surveys (every 4-6 months). We geolocated residents and migration events and mapped the geospatial linkages of sexual partners at the start of sexual partnerships. In a grid composed by 108 cells (nodes; 3kmx3km per cell) covering the surveillance area (438km2), we calculated the degree of connectivity and centrality of the nodes and examined their association with HIV prevalence and incidence per cell. Of 2401 new sexual partnerships, 21% (n = 495) had both partners living within the surveillance area at the start of sexual partnerships, and 76% (376/495) were linked to the geographic HIV cluster with high HIV prevalence identified in a peri-urban community. Overall, 57 nodes had at least one connection to another node. The nodes in the peri-urban cluster had higher connectivity (mean = 19, range: 9-32), compared to outside the cluster (6, range: 1-16). The node's degree of connectivity was positively associated with HIV prevalence of the cell (Pearson correlation coefficient = 0.67; p <0.005). The peri-urban cluster contained nine of the 10 nodes that composed of a single large central module in the community. About 17% of sexual partnerships (n = 421) were formed between a resident and a non-resident partner who out-migrated. Most of these non-resident partners lived in KwaZulu-Natal (86.7%), followed by Gauteng (9.7%), and the median distance between a resident and a non-resident partner was 50.1km (IQR: 23.2-177.2). We found that the peri-urban HIV cluster served as the highly connected central node of the network for sexual partnership formation. The network was also connected beyond the surveillance area across South Africa. Understanding spatial sexual network can improve the provision of spatially targeted and effective interventions.
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Since introduction into Brazil in 2014, chikungunya virus (CHIKV) has presented sustained transmission, although much is unknown about its circulation in the midwestern states. Here, we analyze 24 novel partial and near complete CHIKV genomes from Cuiaba, an urban metropolis located in the Brazilian midwestern state of Mato Grosso (MT). Nanopore technology was used for sequencing CHIKV complete genomes. Phylogenetic and epidemiological approaches were used to explore the recent spatio-temporal evolution and spread of the CHIKV-ECSA genotype in Midwest Brazil as well as in the Americas. Epidemiological data revealed a reduction in the number of reported cases over 2018-2020, likely as a consequence of a gradual accumulation of herd-immunity. Phylogeographic reconstructions revealed that at least two independent introductions of the ECSA lineage occurred in MT from a dispersion event originating in the northeastern region and suggest that the midwestern Brazilian region appears to have acted as a source of virus transmission towards Paraguay, a bordering South American country. Our results show a complex dynamic of transmission between epidemic seasons and suggest a possible role of Brazil as a source for international dispersion of the CHIKV-ECSA genotype to other countries in the Americas.
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Febre de Chikungunya/epidemiologia , Febre de Chikungunya/transmissão , Vírus Chikungunya/genética , Genoma Viral/genética , Adolescente , Adulto , Teorema de Bayes , Brasil/epidemiologia , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/isolamento & purificação , Monitoramento Epidemiológico , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Análise Espaço-Temporal , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
Genetic analysis of HIV-1 is essential to improve treatment strategies and select epitopes for vaccine programs. The objective of this study was to determine whether known CD4+ and CD8+ epitopes were present in Brazilian HIV-1 strains. We used previously described CD8+ and CD4+ epitopes from the Los Alamos laboratory to search for these epitopes in the Brazilian sequences using the HIVbase program and we compared the frequency results with the analyses using physical-chemical profile tools from Network Protein Sequence Analysis (NPSA), and the SYFPEITHI program. Furthermore, this analysis was carried out with the Prosite tool using the GeneDoc program and ds/dn analyses using the Synonymous Nonsynonymous Analysis Program (SNAP). The HIVbase epitope mapping demonstrated that 30 CD8+ and 6 CD4+ epitopes were present in the Brazilian sequences at a high frequency. Only two of these epitopes were heavily glycosylated. Interestingly, ds/dn analyses showed evidence of purifying selective pressure. These types of analyses could be useful for the assessment of possible vaccine efficiency in populations.
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Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos/genética , Produtos do Gene env/genética , Infecções por HIV/virologia , HIV-1/genética , Brasil , HIV-1/classificação , HIV-1/imunologia , HumanosRESUMO
Approximately 35 million people worldwide are infected with human immunodeficiency virus (HIV) around 3.2 million of whom are children under 15 years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all infections in children. Despite great advances in the prevention of MTCT in Brazil, children are still becoming infected. Samples from 19 HIV-1-infected families were collected. DNA was extracted and fragments from gag, pol, and env were amplified and sequenced directly. Phylogenetic reconstruction was performed. Drug resistance analyses were performed in pol and env sequences. We found 82.1% of subtype B and 17.9% of BF recombinants. A prevalence of 43.9% drug resistance-associated mutations in pol sequences was identified. Of the drug-naive children 33.3% presented at least one mutation related to protease inhibitor/nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor (PI/NRTI/NNRTI) resistance. The prevalence of transmitted drug resistance mutations was 4.9%. On env we found a low prevalence of HR1 (4.9%) and HR2 (14.6%) mutations.
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Variação Genética , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas , Adolescente , Adulto , Brasil , Criança , Pré-Escolar , Análise por Conglomerados , Estudos Transversais , Farmacorresistência Viral , Feminino , Genótipo , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Recombinação Genética , Análise de Sequência de DNA , Homologia de Sequência , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
The analysis of genetic data for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type 1 (HTLV-1) is essential to improve treatment and public health strategies as well as to select strains for vaccine programs. However, the analysis of large quantities of genetic data requires collaborative efforts in bioinformatics, computer biology, molecular biology, evolution, and medical science. The objective of this study was to review and improve the molecular epidemiology of HIV-1 and HTLV-1 viruses isolated in Brazil using bioinformatic tools available in the Laboratório Avançado de Sáude Pública (Lasp) bioinformatics unit. The analysis of HIV-1 isolates confirmed a heterogeneous distribution of the viral genotypes circulating in the country. The Brazilian HIV-1 epidemic is characterized by the presence of multiple subtypes (B, F1, C) and B/F1 recombinant virus while, on the other hand, most of the HTLV-1 sequences were classified as Transcontinental subgroup of the Cosmopolitan subtype. Despite the high variation among HIV-1 subtypes, protein glycosylation and phosphorylation domains were conserved in the pol, gag, and env genes of the Brazilian HIV-1 strains suggesting constraints in the HIV-1 evolution process. As expected, the functional protein sites were highly conservative in the HTLV-1 env gene sequences. Furthermore, the presence of these functional sites in HIV-1 and HTLV-1 strains could help in the development of vaccines that pre-empt the viral escape process.
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Humanos , Biologia Computacional , HIV-1 , Vírus Linfotrópico T Tipo 1 Humano/genética , Sequência de Aminoácidos , Sequência de Bases , Brasil , Genótipo , Glicosilação , HIV-1 , Vírus Linfotrópico T Tipo 1 Humano/classificação , Epidemiologia Molecular , Dados de Sequência Molecular , FosforilaçãoRESUMO
Genetic analysis of HIV-1 is essential to improve treatment strategies and select epitopes for vaccine programs. The objective of this study was to determine whether known CD4+ and CD8+ epitopes were present in Brazilian HIV-1 strains. We used previously described CD8+ and CD4+ epitopes from the Los Alamos laboratory to search for these epitopes in the Brazilian sequences using the HIVbase program and we compared the frequency results with the analyses using physical-chemical profile tools from Network Protein Sequence Analysis (NPSA), and the SYFPEITHI program. Furthermore, this analysis was carried out with the Prosite tool using the GeneDoc program and ds/dn analyses using the Synonymous Nonsynonymous Analysis Program (SNAP). The HIVbase epitope mapping demonstrated that 30 CD8+ and 6 CD4+ epitopes were present in the Brazilian sequences at a high frequency. Only two of these epitopes were heavily glycosylated. Interestingly, ds/dn analyses showed evidence of purifying selective pressure. These types of analyses could be useful for the assessment of possible vaccine efficiency in populations.