Comprehensive Characterization of HIV-1 Molecular Epidemiology and Demographic History in the Brazilian Region Most Heavily Affected by AIDS

ABSTRACTThe high incidence of AIDS cases and the dominance of HIV-1 subtype C infections are two features that distinguish the HIV-1 epidemic in the two southernmost Brazilian states (Rio Grande do Sul [RS] and Santa Catarina [SC]) from the epidemic in other parts of the country. Nevertheless, previous studies on HIV molecular epidemiology were conducted mainly in capital cities, and a more comprehensive understanding of factors driving this unique epidemic in Brazil is necessary. Blood samples were collected from individuals in 13 municipalities in the Brazilian southern region. HIV-1envandpolgenes were submitted to phylogenetic analyses for assignment of subtype, and viral population phylodynamics were reconstructed by applying Skygrid and logistic coalescent models in a Bayesian analysis. A high prevalence of subtype C was observed in all sampled locations; however, an increased frequency of recombinant strains was found in RS, with evidence for new circulating forms (CRFs). In the SC state, subtype B and C epidemics were associated with distinct exposure groups. Although logistic models estimated similar growth rates for HIV-1 subtype C (HIV-1C) and HIV-1B, a Skygrid plot reveals that the former epidemic has been expanding for a longer time. Our results highlight a consistent expansion of HIV-1C in south Brazil, and we also discuss how heterosexual and men who have sex with men (MSM) transmission chains might have impacted the current prevalence of HIV-1 subtypes in this region.IMPORTANCEThe AIDS epidemic in south Brazil is expanding rapidly, but the circumstances driving this condition are not well known. A high prevalence of HIV-1 subtype C was reported in the capital cities of this region, in contrast to the subtype B dominance in the rest of the country. This study sought to comparatively investigate the HIV-1 subtype B and C epidemics by sampling individuals from several cities in the two states with the highest AIDS incidences in Brazil. Our analyses showed distinct epidemic growth curves for the two epidemics, and we also found evidence suggesting that separate transmission chains may be impacting the viral phylodynamics and the emergence of new recombinant forms.

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Identification of a New HIV-1 BC Intersubtype Circulating Recombinant Form (CRF108_BC) in Spain

Viruses ◽

10.3390/v13010093 ◽

2021 ◽

Vol 13 (1) ◽

pp. 93

Author(s):

Javier E. Cañada ◽

Elena Delgado ◽

Horacio Gil ◽

Mónica Sánchez ◽

Sonia Benito ◽

...

Keyword(s):

Phylogenetic Analyses ◽

Basque Country ◽

Recent Common Ancestor ◽

Subtype C ◽

Northern Spain ◽

Most Recent Common Ancestor ◽

Phylogenetic Cluster ◽

Subtype B ◽

Definition Of ◽

Hiv 1

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.

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Evolutionary dynamics of HIV-1 subtype C in Brazil

Scientific Reports ◽

10.1038/s41598-021-02428-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bernardino Souto ◽

Vera Triunfante ◽

Ana Santos-Pereira ◽

Joana Martins ◽

Pedro M. M. Araújo ◽

...

Keyword(s):

Evolutionary Dynamics ◽

Lower Probability ◽

American Continent ◽

Subtype C ◽

The South ◽

Subtype B ◽

Treatment Naïve ◽

Viral Sequences ◽

Hiv 1 ◽

South Brazil

AbstractThe extensive genetic diversity of HIV-1 is a major challenge for the prevention and treatment of HIV-1 infections. Subtype C accounts for most of the HIV-1 infections in the world but has been mainly localized in Southern Africa, Ethiopia and India. For elusive reasons, South Brazil harbors the largest HIV-1 subtype C epidemic in the American continent that is elsewhere dominated by subtype B. To investigate this topic, we collected clinical data and viral sequences from 2611 treatment-naïve patients diagnosed with HIV-1 in Brazil. Molecular epidemiology analysis supported 35 well-delimited transmission clusters of subtype C highlighting transmission within South Brazil but also from the South to all other Brazilian regions and internationally. Individuals infected with subtype C had lower probability to be deficient in CD4+ T cells when compared to subtype B. The HIV-1 epidemics in the South was characterized by high female-to-male infection ratios and women-to-child transmission. Our results suggest that HIV-1 subtype C probably takes advantage of longer asymptomatic periods to maximize transmission and is unlikely to outcompete subtype B in settings where the infection of women is relatively less relevant. This study contributes to elucidate factors possibly underlying the geographical distribution and expansion patterns of the most spread HIV-1 subtypes.

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Molecular Epidemiology of HIV-1 in Brazil: High Prevalence of HIV-1 Subtype B and Identification of an HIV-1 Subtype D Infection in the City of Rio de Janeiro, Brazil

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology ◽

10.1097/00042560-199808150-00011 ◽

1998 ◽

Vol 18 (5) ◽

pp. 488-494 ◽

Cited By ~ 50

Author(s):

Mariza G. Morgado ◽

Monick L. Guimarães ◽

Carmen B. G. Gripp ◽

Catia I. Costa ◽

Ivan Neves ◽

...

Keyword(s):

Molecular Epidemiology ◽

Rio De Janeiro ◽

Subtype B ◽

High Prevalence ◽

The City ◽

Hiv 1

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Molecular Epidemiology of HIV-1 in Venezuela: High Prevalence of HIV-1 Subtype B and Identification of a B/F Recombinant Infection

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/00126334-200303010-00015 ◽

2003 ◽

Vol 32 (3) ◽

pp. 338-344 ◽

Cited By ~ 15

Author(s):

Erika Castro ◽

Gloria Echeverría ◽

Leopoldo Deibis ◽

Beatríz González de Salmen ◽

Aline Dos Santos Moreira ◽

...

Keyword(s):

Molecular Epidemiology ◽

Subtype B ◽

High Prevalence ◽

Hiv 1

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Genetic Diversity and Drug Resistance of HIV-1 CRF55_01B in Guangdong, China

Current HIV Research ◽

10.2174/1570162x18666200415140652 ◽

2020 ◽

Vol 18 (3) ◽

pp. 210-218

Author(s):

Guolong Yu ◽

Yan Li ◽

Xuhe Huang ◽

Pingping Zhou ◽

Jin Yan ◽

...

Keyword(s):

Genetic Diversity ◽

Drug Resistance ◽

Reverse Transcriptase ◽

Phylogenetic Analyses ◽

Resistance Mutations ◽

Protease Inhibition ◽

Subtype B ◽

Primary Drug Resistance ◽

Hiv 1 ◽

Primary Drug

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

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022 A heterosexual outbreak in Doncaster involving subtype B of HIV-1: molecular epidemiology as a supplement to contact tracing

HIV Medicine ◽

10.1046/j.1468-1293.2000.00024-43.x ◽

2000 ◽

Vol 1 (3) ◽

pp. 172-172

Author(s):

A Hayman ◽

T Moss ◽

C Arnold ◽

l Naylor-Adamson ◽

J Hawkswell ◽

...

Keyword(s):

Molecular Epidemiology ◽

Contact Tracing ◽

Subtype B ◽

Hiv 1

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An Integrated Framework for the Inference of Viral Population History From Reconstructed Genealogies

Genetics ◽

10.1093/genetics/155.3.1429 ◽

2000 ◽

Vol 155 (3) ◽

pp. 1429-1437

Author(s):

Oliver G Pybus ◽

Andrew Rambaut ◽

Paul H Harvey

Keyword(s):

Maximum Likelihood ◽

Sequence Data ◽

Demographic History ◽

Population History ◽

Maximum Likelihood Estimates ◽

Viral Population ◽

True Parameter ◽

Subtype B ◽

Exponential Growth Model ◽

Parameter Values

Abstract We describe a unified set of methods for the inference of demographic history using genealogies reconstructed from gene sequence data. We introduce the skyline plot, a graphical, nonparametric estimate of demographic history. We discuss both maximum-likelihood parameter estimation and demographic hypothesis testing. Simulations are carried out to investigate the statistical properties of maximum-likelihood estimates of demographic parameters. The simulations reveal that (i) the performance of exponential growth model estimates is determined by a simple function of the true parameter values and (ii) under some conditions, estimates from reconstructed trees perform as well as estimates from perfect trees. We apply our methods to HIV-1 sequence data and find strong evidence that subtypes A and B have different demographic histories. We also provide the first (albeit tentative) genetic evidence for a recent decrease in the growth rate of subtype B.

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Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

International Journal of Molecular Sciences ◽

10.3390/ijms22105304 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5304

Author(s):

Ana Santos-Pereira ◽

Vera Triunfante ◽

Pedro M. M. Araújo ◽

Joana Martins ◽

Helena Soares ◽

...

Keyword(s):

Drug Resistance ◽

People Living With Hiv ◽

Resistance Mutations ◽

Subtype C ◽

Viral Loads ◽

Drug Resistance Mutations ◽

Subtype B ◽

Low Prevalence ◽

Living With Hiv ◽

Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

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Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa042 ◽

2020 ◽

Vol 75 (6) ◽

pp. 1567-1574

Author(s):

Daniela Sánchez ◽

Solange Arazi Caillaud ◽

Ines Zapiola ◽

Silvina Fernandez Giuliano ◽

Rosa Bologna ◽

...

Keyword(s):

Drug Resistance ◽

Current Knowledge ◽

Phylogenetic Analyses ◽

Genotypic Diversity ◽

Resistance Testing ◽

Cross Resistance ◽

Resistance Mutations ◽

Middle Income ◽

Subtype B ◽

Hiv 1

Abstract Background Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate. Materials and methods HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses. Results Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%), 7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping. INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs. Conclusions Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the use of INIs.

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