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1.
PLoS One ; 12(12): e0189705, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29244833

RESUMO

Currently, data on HIV-1 circulating strains among men who have sex with men (MSM) in Argentina is scarce. In South America, the distribution and the prevalence of BF recombinants are dissimilar and exhibit an underappreciated heterogeneity of recombinant structures. Here, we studied for the first time the genetic diversity of HIV-1 BF recombinants and their evolution over time through in-depth phylogenetic analysis and multiple recombination detection methods involving 337 HIV-1 nucleotide sequences (25 near full-length (NFL) and 312 partial pol gene) obtained from Argentinean MSM. The recombination profiles were studied using multiple in silico tools to characterize the genetic mosaicism, and phylogenetic approaches to infer their relationships. The evolutionary history of BF recombinants and subtype B sequences was reconstructed by a Bayesian coalescent-based method. By phylogenetic inference, 81/312 pol sequences clustered within BF clade. Of them, 46 sequences showed a genetic mosaic with CRF12_BF-like patterns, including plausible second-generation recombinants. Other CRFs_BF like (CRF17, 28, 29, 39, 42, 44, 47) and probable URFs_BF were less frequently found. Phylogenetic and recombination analyses on NFL sequences allowed a meticulous definition of new BF mosaics of genomic patterns. The Bayesian analyses pointed out quite consistent onset dates for the CRFs_BF clade based on B and F gene datasets (~1986 and ~1991 respectively). These results indicate that the CRFs_BF variants have been circulating among Argentinean MSM for about 30 years. This study reveals, through growing evidence showing the importance of MSM in the dynamics of the HIV-1 epidemic in Argentina, the coexistence of CRF12_BF-like and high diversity of strains exhibiting several BF mosaic patterns, including non-reported URFs that may reflect active clusters as potential intervention targets to hinder HIV-1 transmission.


Assuntos
Variação Genética , Infecções por HIV/genética , HIV-1/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética , Adulto , Argentina , Evolução Molecular , Genoma Viral/genética , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Masculino , Filogenia , Minorias Sexuais e de Gênero
2.
AIDS Res Hum Retroviruses ; 31(9): 932-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26122980

RESUMO

This study reports on the drug resistance profiles for HIV-infected pediatrics in Jamaica who have been exposed to antiretroviral therapy (ART). The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. The protease-reverse transcriptase (Pro-RT) region of the genome was amplified from 40 samples, sequenced, and analyzed for the identification of antiretroviral resistance-associated mutations (RAMs). All isolates belonged to subtype B and 39 possessed multiple RAMs in the reverse transcriptase genes that would compromise the efficacy of drugs being used to treat these patients. Four isolates possessed RAMs in the protease genes. The overall frequency of HIV drug resistance was 95%. The high frequency of drug resistance is supported by epidemiological data that revealed an equally high frequency of treatment failure (98%) among the study participants. The results of this study indicate the urgent need for greater access to drug resistance testing in Jamaica.


Assuntos
Farmacorresistência Viral , Genes pol , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Transcriptase Reversa do HIV/genética , HIV-1/genética , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Variação Genética , HIV-1/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Jamaica , Dados de Sequência Molecular , Mutação , Filogenia , Análise de Sequência de DNA , Falha de Tratamento
3.
J Virol ; 88(6): 3058-66, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24335292

RESUMO

The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.


Assuntos
Variação Genética , Febre Lassa/prevenção & controle , Vírus Lassa/genética , Vírus Lassa/imunologia , Vacinas Virais/genética , Animais , Callithrix , Chlorocebus aethiops , Humanos , Imunidade Celular , Febre Lassa/imunologia , Febre Lassa/virologia , Macaca mulatta , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Células Vero , Vacinas Virais/imunologia
4.
Virology ; 443(2): 306-12, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23791226

RESUMO

Mutations in the HIV-1 proviral genomes delay the progression of the disease. We compared the mutation status in full-length proviral genomes of 23 HIV-infected patients with undetectable viral loads in the absence of therapy named natural viral suppressors (NVS) or Elite Controllers with 23 HIV-infected controls (10 patients on HAART treatment and 13 untreated patients). Provirus DNA was extracted from PBMC for amplification and sequencing to determine the mutation status. Nine (39 %) of the 23 NVS patients had defective proviral genomes, compared to 4 of the treated controls (40%, p = 0.96) and only one of the untreated controls (8%, p = 0.059). Most of the defective genomes resulted from Gto-A hypermutation. Among patients with hypermutation, the rate ratio for mutation was significantly higher for the NVS compared to treated controls (p = 0.043). Our data suggests that inactivation of the virus through the APOBEC3G system may contribute to the NVS phenotype.


Assuntos
HIV-1/genética , HIV-1/patogenicidade , Mutação , Inativação de Vírus , Terapia Antirretroviral de Alta Atividade , DNA Viral/análise , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Genoma Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Leucócitos Mononucleares/virologia , Masculino , Dados de Sequência Molecular , Filogenia , Provírus/genética , Análise de Sequência de DNA
5.
AIDS ; 27(4): 553-61, 2013 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-23079810

RESUMO

BACKGROUND: In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. METHODS: Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. RESULTS: One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). CONCLUSIONS: At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.


Assuntos
Adenina/análogos & derivados , Farmacorresistência Viral , Soropositividade para HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Organofosfonatos/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Zidovudina/administração & dosagem , Adenina/administração & dosagem , Adulto , Estudos Transversais , Esquema de Medicação , Farmacorresistência Viral/imunologia , Feminino , Genótipo , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/imunologia , HIV-1/genética , Humanos , Masculino , Mutação de Sentido Incorreto , Nigéria/epidemiologia , RNA Viral , Estudos Retrospectivos , Tenofovir , Falha de Tratamento , Carga Viral/efeitos dos fármacos
6.
Ecohealth ; 9(1): 17-23, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22395958

RESUMO

Hunting and butchering of wildlife in Central Africa are known risk factors for a variety of human diseases, including HIV/AIDS. Due to the high incidence of human exposure to body fluids of non-human primates, the significant prevalence of simian immunodeficiency virus (SIV) in non-human primates, and hunting/butchering associated cross-species transmission of other retroviruses in Central Africa, it is possible that SIV is actively transmitted to humans from primate species other than mangabeys, chimpanzees, and/or gorillas. We evaluated SIV transmission to humans by screening 2,436 individuals that hunt and butcher non-human primates, a population in which simian foamy virus and simian T-lymphotropic virus were previously detected. We identified 23 individuals with high seroreactivity to SIV. Nucleic acid sequences of SIV genes could not be detected, suggesting that SIV infection in humans could occur at a lower frequency than infections with other retroviruses, including simian foamy virus and simian T-lymphotropic virus. Additional studies on human populations at risk for non-human primate zoonosis are necessary to determine whether these results are due to viral/host characteristics or are indicative of low SIV prevalence in primate species consumed as bushmeat as compared to other retroviruses in Cameroon.


Assuntos
Transmissão de Doença Infecciosa/veterinária , Carne/virologia , Primatas/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/diagnóstico , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/patogenicidade , Zoonoses/transmissão , Animais , Camarões , Estudos de Coortes , Microbiologia de Alimentos , Humanos
7.
J Infect Dis ; 205(8): 1239-47, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22357663

RESUMO

BACKGROUND: Acute phase of human immunodeficiency virus (HIV) infection (AHI) may account for a significant proportion of HIV-1 transmission. We identified and characterized individuals in Nigeria with AHI. METHODS: Individuals were tested using a combination of rapid HIV testing in mobile units and laboratory-based specimen pooling for nucleic acid amplification testing. Genome sequences were characterized. A linear segmented regression model was fit to serial viral load (VL) measurements to characterize early VL profiles. RESULTS: Sixteen AHIs were identified from 28 655 persons screened. Specimens were genotyped: 7 (43.8%) were CRF02_AG, 6 (37.5%) were subtype G, 1 (6.3%) was CRF06_cpx, and 2 (12.5%) were unique recombinant forms. No antiretroviral resistance mutations were detected. The mean duration of high VL burden from peak to nadir was 76 days (95% confidence interval [CI], 58-93 days), and the mean rate of viremic control was -0.66 log(10) VL per month. The mean VL at set-point was 4.5 log(10) copies/mL (95% CI, 3.9-5.1 log(10) copies/mL). CONCLUSIONS: This study is the first to characterize AHI among Nigerians identified as HIV infected before seroconversion who would be otherwise missed by conventional HIV testing. Infections by HIV subtypes in Nigeria exhibit long periods of high viral burden, which can contribute to increased transmissibility.


Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/epidemiologia , HIV-1 , Doença Aguda , Adolescente , Adulto , Farmacorresistência Viral/genética , Feminino , Genótipo , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Dados de Sequência Molecular , Nigéria/epidemiologia , Filogenia , RNA Viral/sangue , Fatores de Risco , Carga Viral , Adulto Jovem
8.
AIDS Res Hum Retroviruses ; 28(5): 527-30, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21902588

RESUMO

A recent HIV-1 molecular epidemiology survey in Singapore identified a novel CRF01_AE/B recombinant form, which accounted for 13 (11.9%) of 109 patient samples. Peripheral blood mononuclear cell DNA from three of these 13 patients was used to generate near full-length sequences to characterize the novel CRF01_AE/B recombinant form. The three isolates had a recombinant structure composed of CRF01_AE and subtype B, and shared identical breakpoints. As the three patients were not epidemiologically linked, this recombinant form has been designated CRF51_01B. Identification of the novel recombinant forms indicates ongoing active HIV-1 transmission in Singapore.


Assuntos
Soropositividade para HIV/genética , HIV-1/genética , Adulto , Sequência de Bases , Genótipo , Soropositividade para HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Singapura/epidemiologia
9.
AIDS Res Hum Retroviruses ; 28(8): 923-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22049946

RESUMO

This study reports on the drug resistance profiles for HIV-infected adults in Jamaica using genotypic methods. The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. Epidemiological data were documented for each patient, blood was collected by venous puncture, and plasma was separated and stored. Viral RNA was extracted and analyzed for mutations in the viral genome by the amplification of the protease and reverse transcriptase (Pro-RT) regions using a nested PCR method. The rate of drug resistance among treatment-experienced individuals was 35%, while treatment-naive individuals showed a prevalence of 29%. The overall prevalence of drug resistance mutations in Jamaicans was consistent with the increased use of antiretroviral drugs in the region, with many of the mutations detected reducing susceptibility to the drugs commonly used to treat Jamaican patients. These results indicate the need for regular drug resistant surveillance to guide treatment strategies.


Assuntos
Antirretrovirais/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/genética , HIV/genética , Adulto , Antirretrovirais/uso terapêutico , HIV/efeitos dos fármacos , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Jamaica , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Filogenia , RNA Viral
10.
Virol J ; 8: 392, 2011 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-21824422

RESUMO

BACKGROUND: Genetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B. OBJECTIVES: The aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfection STUDY DESIGN: Blood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene pol was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed. RESULTS: Five dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains. CONCLUSIONS: Our results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Argentina , Sangue/virologia , Análise por Conglomerados , Farmacorresistência Viral , HIV-1/genética , Humanos , Masculino , Mutação de Sentido Incorreto , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
11.
PLoS One ; 6(6): e19995, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21698149

RESUMO

BACKGROUND: In Trinidad and the wider Caribbean, subtype B Human Immunodeficiency Virus-type 1 (HIV-1B) overwhelmingly accounts for HIV infection among heterosexuals; this contrasts with the association of HIV-1B with homosexual transmission and injecting drug use globally. The HIV envelope contains genetic determinants of cell tropism and evasion from immune attack. In this study we investigate the genetic properties of the env V1-C4 of HIV-1B soon after transmission to Trinidadian heterosexuals. This will reveal distinctive genetic features of the strains that cause the HIV-1B epidemic in Trinidad and generate insights to better understand their properties. METHODOLOGY/PRINCIPAL FINDINGS: Quasispecies sampling was performed on the env V1-C4 of HIV-1B strains soon after transmission to heterosexual Trinidadians in a cohort of seroconverters. Phylogenetic relationships were determined for these quasispecies and the length and number of asparagine (N) linked glycosylation sites (NLGS) in their variable loops compared to that for HIV-1B globally. Signature amino acids within the constant domains of the env V1-C4 were identified for heterosexually transmitted HIV-1B from Trinidad relative to HIV-1B globally. HIV-1B obtained from Trinidadian heterosexuals soon after seroconversion had significantly longer V2 loops with one more glycosylation site, shorter V3 loops and no significant difference in V1 or V4 when compared to HIV-1B obtained soon after seroconversion from infected individuals in the rest of the world. HIV-1B soon after seroconversion and during chronic infection of Trinidadians was not significantly different, suggesting that distinctly long V2 loops are characteristic of HIV-1B in Trinidad. A threonine deletion at position 319 (T319-) along with the substitutions R315K and S440R were found to be distinctly associated with HIV-1B from Trinidad compared to HIV-1B globally. CONCLUSIONS: This finding of distinctive genetic features that are characteristic of HIV-1B strains from Trinidad is consistent with the Trinidad epidemic being established by a founder strain or closely related founder strains of HIV-1B.


Assuntos
Infecções por HIV/virologia , HIV-1/química , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/virologia , Proteínas do Envelope Viral/química , Sequência de Aminoácidos , Estudos de Coortes , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/classificação , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , Filogenia , Fatores de Risco , Homologia de Sequência de Aminoácidos , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/transmissão , Trinidad e Tobago/epidemiologia
12.
AIDS Res Hum Retroviruses ; 27(1): 91-5, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20929350

RESUMO

This study seeks to analyze nearly full-length viral genomes for distinct genetic characteristics that are unique to local or regional strains and to identify regions that have high variability or are highly conserved. Nearly full length sequences of seven HIV-1 samples were obtained to ascertain the circulating subtype diversity in the HIV-1 epidemic in Jamaica as well as conduct detailed sequence analysis. The phylogenetic analysis of the seven sequences showed all the sequences clustering with HIV-1 pure B subtype references. The predicted amino acid sequenced in the V3 loop for the Jamaican samples showed that six samples contained the characteristic conserved tetrapeptide motif GPGR. One occurrence in isolate 09JM.PF09WX displayed a GQGP tetrameric motif similar to that found in a Korean B strain. All seven isolates (100%) were R5 viruses for preferential cofactor usage. These samples were collected from individuals who had tested positive for 1-5 years and were drug naive. The results suggested that the viruses were isolated from patients in the nonprogressive stage of disease. These are early stages in the assessment and the patient should be monitored to predict the progression of the disease and when HAART should begin.


Assuntos
Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , RNA Viral/genética , Adulto , Análise por Conglomerados , Sequência Conservada , Feminino , Genótipo , Geografia , HIV-1/isolamento & purificação , Humanos , Jamaica , Masculino , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA
13.
AIDS Res Hum Retroviruses ; 26(9): 1033-45, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20812894

RESUMO

Cameroon is a country in West Central Africa in which all four groups of HIV-1 (M, N, O, and P), some circulating recombinant forms (CRFs) and unique recombinant forms (URFs) are prevalent. The CRF22 was initially identified through a novel URF strain, 01CM53122, and later defined from two additional sequences; however, the genomic properties of CRF22 have never been demonstrated in detail. In this study, we describe the characterization of five CRF22_01A1 strains, 02CMLT72, 01CM1867LE, 01CM001BBY, 02CM3097MN, and 02CM1917LE, identified in Cameroon without apparent epidemiological links. A typical CRF22_01A1 strain contains five fragments that can be assigned to the CRF01_AE and subsubtype A1 radiations. Forty-eight percent of the genome is classified as CRF01_AE, spanning the entire region of the gag gene, part of the pol gene, and accessory genes as well as the beginning and the end of the env gene and nef gene. Fifty-two percent of the genome is subsubtype A1 including regions mostly in the pol, vif, and env genes. The five CRF22_01A1 viruses formed a deep branch outside the groups of CRF01_AE and displayed similar mosaic structure but were moderately different from the original strain of CRF22_01A1, 01CM53122. Further analysis of the 01CM53122 genome showed that this virus represents a diverse set of mosaic genomes from CRF22_01A1, including a 446-nt segment of 01CM53122 in the env region, but unlike other CRF22 strains, clustered with CRF01_AE rather than the A1 sequence, suggesting that the 01CM53122 strain is a recombinant of CRF22_01A1 and CRF01_AE.


Assuntos
Variação Genética , Genoma Viral , HIV-1/genética , Recombinação Genética , Camarões/epidemiologia , Genes Virais , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Dados de Sequência Molecular , Filogenia , RNA Viral/genética , Análise de Sequência de RNA
14.
Emerg Infect Dis ; 16(10): 1605-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20875290

RESUMO

Human parvovirus 4 infections are primarily associated with parenteral exposure in western countries. By ELISA, we demonstrate frequent seropositivity for antibody to parvovirus 4 viral protein 2 among adult populations throughout sub-Saharan Africa (Burkina Faso, 37%; Cameroon, 25%; Democratic Republic of the Congo, 35%; South Africa, 20%), which implies existence of alternative transmission routes.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/virologia , Parvovirus/imunologia , Adolescente , Adulto , África Subsaariana/epidemiologia , Idoso , Burkina Faso/epidemiologia , Camarões/epidemiologia , Proteínas do Capsídeo/imunologia , Criança , República Democrática do Congo/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , África do Sul/epidemiologia , Adulto Jovem
15.
J Acquir Immune Defic Syndr ; 54(3): 297-303, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20505517

RESUMO

BACKGROUND: HIV-1 subtype B virus is the predominant subtype in HIV-infected individuals in the United States. However, increasing evidence suggests that prevalence of non-B subtypes may be on the rise in the West, and this may have implications for HIV-1 disease surveillance and treatment. The state of Maryland currently has the fourth highest AIDS case report rate in the United States. The goal of this study was to evaluate the prevalence of HIV-1 non-B subtypes in Maryland. The study population included individuals diagnosed with HIV in 2007 through the voluntary counseling and testing sites at the Maryland Department of Health and Mental Hygiene and HIV-infected patients who had genotyping performed at the University of Maryland Medical Center. RESULTS: At the Department of Health and Mental Hygiene sites, 47 unique non-B subtype strains were identified representing a non-B prevalence of 12.9%. These non-B subtypes included CRF02_AG (n = 20), C (n = 11), A (n = 7), G (n = 5), D (n = 1), and unique recombinant forms (n = 3). The non-B patients were predominantly non-Hispanic black (95.7%) with 63.8% female. Although the majority of the HIV subtype B cases (65.3%) were identified from the Baltimore metropolitan area, most (80.9%) of the non-B cases were from the Maryland suburbs of Washington, DC. Among University of Maryland Medical Center patients, there were 30 non-B subtypes, representing a non-B prevalence of 1.9%. The non-B subtypes detected were CRF02_AG (n = 14), C (n = 6), A (n = 6), G (n = 2), D (n = 1), and unique recombinant forms (n = 1). Phylogenetic analysis of the non-B subtypes revealed that viral sequences from both sources were intermixed, confirming that both sampling frames were drawing from the same overall population. CONCLUSIONS: Multiple HIV-1 subtypes exist in the Baltimore-Washington metropolitan area with a significant non-B-infected population in the Maryland suburbs of Washington, DC, suggesting 2 independent epidemics of HIV in Maryland. Population-based surveillance inclusive of groups at higher risk of non-B strains is essential to monitor the prevalence and variations of HIV subtypes in Maryland and the United States.


Assuntos
Surtos de Doenças , Infecções por HIV/epidemiologia , HIV-1 , Adulto , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Humanos , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Prevalência , Adulto Jovem
16.
Retrovirology ; 7: 39, 2010 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-20426823

RESUMO

BACKGROUND: The HIV pandemic disseminated globally from Central West Africa, beginning in the second half of the twentieth century. To elucidate the virologic origins of the pandemic, a cross-sectional study was conducted of the genetic diversity of HIV-1 strains in villagers in 14 remote locations in Cameroon and in hospitalized and STI patients. DNA extracted from PBMC was PCR amplified from HIV(+) subjects. Partial pol amplicons (N = 164) and nearly full virus genomes (N = 78) were sequenced. Among the 3956 rural villagers studied, the prevalence of HIV infection was 4.9%; among the hospitalized and clinic patients, it was 8.6%. RESULTS: Virus genotypes fell into two distinctive groups. A majority of the genotyped strains (109/164) were the circulating recombinant form (CRF) known to be endemic in West Africa and Central West Africa, CRF02_AG. The second most common genetic form (9/164) was the recently described CRF22_01A1, and the rest were a collection of 4 different subtypes (A2, D, F2, G) and 6 different CRFs (-01, -11, -13, -18, -25, -37). Remarkably, 10.4% of HIV-1 genomes detected (17/164) were heretofore undescribed unique recombinant forms (URF) present in only a single person. Nearly full genome sequencing was completed for 78 of the viruses of interest. HIV genetic diversity was commonplace in rural villages: 12 villages each had at least one newly detected URF, and 9 villages had two or more. CONCLUSIONS: These results show that while CRF02_AG dominated the HIV strains in the rural villages, the remainder of the viruses had tremendous genetic diversity. Between the trans-species transmission of SIVcpz and the dispersal of pandemic HIV-1, there was a time when we hypothesize that nascent HIV-1 was spreading, but only to a limited extent, recombining with other local HIV-1, creating a large variety of recombinants. When one of those recombinants began to spread widely (i.e. became epidemic), it was recognized as a subtype. We hypothesize that the viruses in these remote Cameroon villages may represent that pre-epidemic stage of viral evolution.


Assuntos
Variação Genética , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Recombinação Genética , Adulto , Camarões , Análise por Conglomerados , Estudos Transversais , DNA Viral/genética , DNA Viral/isolamento & purificação , Evolução Molecular , Genoma Viral , Genótipo , HIV-1/isolamento & purificação , Hospitais , Humanos , Leucócitos Mononucleares/virologia , Dados de Sequência Molecular , População Rural , Análise de Sequência de DNA , Homologia de Sequência , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
17.
AIDS Res Hum Retroviruses ; 25(9): 853-60, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19689193

RESUMO

This study aimed to determine HIV, HCV, and syphilis prevalence and correlates, and to characterize the molecular epidemiology of HIV-1 among injecting drug users (IDUs) in Dushanbe, Tajikistan. A cross-sectional study assessing risk factors for HIV and HCV through an interview administered survey was conducted. A total of 491 active adult IDUs were recruited from May to November 2004 in Dushanbe, Tajikistan. HIV-1 antibody status was determined with rapid testing and confirmed with ELISA. HCV antibody testing was conducted using a BIOELISA HCV kit. HIV-1 subtyping was done on a subset with full-length sequencing. Correlates of HIV and HCV infection were assessed using logistic regression. Overall prevalence of HIV was 12.1%, HCV was 61.3%, and syphilis was 15.7%. In a multivariate logistic regression model controlling for gender and ethnicity, daily injection of narcotics [odds ratio (OR) OR 3.22] and Tajik nationality (OR 7.06) were significantly associated with HIV status. Tajik nationality (OR 1.91), history of arrest (OR 2.37), living/working outside Tajikistan in the past 10 years (OR 2.43), and daily injection of narcotics (OR 3.26) were significantly associated with HCV infection whereas being female (OR 0.53) and always using a sterile needle (OR 0.47) were inversely associated with HCV infection. Among 20 HIV-1-positive IDU with specimens available for typing, 10 were subtype A, 9 were CRF02_AG, and one was an A-CRF02_AG recombinant. Epidemics of HIV-1, HCV, and drug use are underway in Dushanbe. The molecular epidemiology is distinctive, with West African variants accounting for roughly 50% of prevalent infections. Targeted prevention programs offering both needle exchange programs and opiate substitution therapies are urgently called for to prevent the further spread of HIV and HCV in Tajikistan.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite C/epidemiologia , Hepatite C/virologia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Comorbidade , Estudos Transversais , Feminino , Genótipo , Anticorpos Anti-HIV/sangue , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Epidemiologia Molecular , RNA Viral/genética , Fatores de Risco , Estudos Soroepidemiológicos , Sífilis/epidemiologia , Tadjiquistão/epidemiologia , Adulto Jovem
18.
Virology ; 391(1): 140-7, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19577266

RESUMO

The global acquired immunodeficiency syndrome (AIDS) pandemic is thought to have arisen by the transmission of human immunodeficiency virus (HIV-1)-like viruses from chimpanzees in southeastern Cameroon to humans. TRIM5alpha is a restriction factor that can decrease the susceptibility of cells of particular mammalian species to retrovirus infection. A survey of TRIM5 genes in 127 indigenous individuals from southeastern Cameroon revealed that approximately 4% of the Baka pygmies studied were heterozygous for a rare variant with a stop codon in exon 8. The predicted product of this allele, TRIM5 R332X, is truncated in the functionally important B30.2(SPRY) domain, does not restrict retrovirus infection, and acts as a dominant-negative inhibitor of wild-type human TRIM5alpha. Thus, some indigenous African forest dwellers potentially exhibit diminished TRIM5alpha function; such genetic factors, along with the high frequency of exposure to chimpanzee body fluids, may have predisposed to the initial cross-species transmission of HIV-1-like viruses.


Assuntos
População Negra/genética , Proteínas de Transporte/genética , Alelos , Fatores de Restrição Antivirais , Camarões , Linhagem Celular , Éxons , Genótipo , Infecções por HIV/genética , Humanos , Análise de Sequência de DNA , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases
19.
PLoS One ; 4(3): e4814, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19279683

RESUMO

BACKGROUND: The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted. METHODOLOGY/PRINCIPAL FINDINGS: Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic. CONCLUSIONS: The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.


Assuntos
Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Sequência de Bases , Primers do DNA , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Humanos , Filogenia , Reação em Cadeia da Polimerase , RNA Viral/isolamento & purificação , Índias Ocidentais/epidemiologia
20.
PLos One ; 4(3): [1-5], mar. 2009. tabilus
Artigo em Inglês | MedCarib | ID: med-17878

RESUMO

BACKGROUND: The molecular epidemiology of HIV-1 in the Caribbean has been described using partial genome sequencing; subtype B is the most common subtype in multiple countries. To expand our knowledge of this, nearly full genome amplification, sequencing and analysis was conducted. METHODOLOGY/PRINCIPAL FINDINGS: Virion RNA from sera collected in Haiti, Dominican Republic, Jamaica and Trinidad and Tobago were reverse transcribed, PCR amplified, sequenced and phylogenetically analyzed. Nearly full genomes were completed for 15 strains; partial pol was done for 67 strains. All but one of the 67 strains analyzed in pol were subtype B; the exception was a unique recombinant of subtypes B and C collected in the Dominican Republic. Of the nearly full genomes of 14 strains that were subtype B in pol, all were subtype B from one end of the genome to the other and not inter-subtype recombinants. Surprisingly, the Caribbean subtype B strains clustered significantly with each other and separate from subtype B from other parts of the pandemic. CONCLUSIONS: The more complete analysis of HIV-1 from 4 Caribbean countries confirms previous research using partial genome analysis that the predominant subtype in circulation was subtype B. The Caribbean strains are phylogenetically distinct from other subtype B strains although the biological meaning of this finding is unclear.


Assuntos
Humanos , HIV-1 , Genoma Humano , Trinidad e Tobago , Haiti , República Dominicana , Jamaica , Região do Caribe
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