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 TratamentoRESUMO
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 ViralRESUMO
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 DNARESUMO
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/epidemiologiaRESUMO
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 CaribeRESUMO
The objective of this study was to determine the prevalence and genetic variability of human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted infections (STIs) among 205 patients with clinical diagnosis of tuberculosis (TB) in Buenos Aires in 2001. Infections with hepatitis B virus (HBV), HIV-1, hepatitis C virus (HCV), Treponema pallidum and human T-cell lymphotropic virus types I/II were diagnosed in 37/187 (19.8 %), 35/205 (17.1 %), 22/187 (11.8 %), 13/187 (7.0 %) and 4/181 (2.2 %) patients, respectively. Almost one in three participants (33.1 %) presented at least one infection in addition to TB. Multiresistance to TB drugs (isoniazid plus rifampicin) was detected in the isolates recovered from three patients. Injecting drug use was detected as the main risk factor for HIV, HBV and HCV infections. Of ten patients who died, eight were infected with HIV. HIV genetic characterization showed the presence of two different subtypes. Env subtype F was found in 13/24 samples (54.2 %) and subtype B in 11/24 samples (45.8 %) by heteroduplex mobility assay. Sequencing of the protease/RT region was performed in ten samples: three were characterized as subtype B and seven as B/F recombinants by bootscanning analysis. Phylogenetic analysis of four full-length sequences showed that three were the circulating recombinant form CRF12_BF. The results of this study suggest an urgent need to detect HIV infection in high-risk groups to prevent future HIV transmission as well as morbidity and mortality associated with TB by providing highly active antiretroviral therapy (HAART) and/or TB treatment. Collaboration between TB and HIV programmes seems to be the best approach to decrease the incidence of these diseases, especially in high-prevalence HIV settings.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/epidemiologia , Tuberculose/epidemiologia , Adolescente , Adulto , Argentina/epidemiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/isolamento & purificação , Hepacivirus/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Fatores de Risco , Análise de Sequência de DNA , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/virologia , Siphoviridae , Abuso de Substâncias por Via Intravenosa/complicações , Treponema pallidum/isolamento & purificaçãoRESUMO
BACKGROUND: A cross-sectional study on 625 Female Sex Workers (FSWs) was conducted between 2000 and 2002 in 6 cities in Argentina. This study describes the genetic diversity and the resistance profile of the HIV-infected subjects. RESULTS: Seventeen samples from HIV positive FSWs were genotyped by env HMA, showing the presence of 9 subtype F, 6 subtype B and 2 subtype C. Sequence analysis of the protease/RT region on 16 of these showed that 10 were BF recombinants, three were subtype B, two were subtype C, and one sample presented a dual infection with subtype B and a BF recombinant. Full-length genomes of five of the protease/RT BF recombinants were also sequenced, showing that three of them were CRF12_BF. One FSW had a dual HIV-1 infection with subtype B and a BF recombinant. The B sections of the BF recombinant clustered closely with the pure B sequence isolated from the same patient. Major resistance mutations to antiretroviral drugs were found in 3 of 16 (18.8%) strains. CONCLUSION: The genetic diversity of HIV strains among FSWs in Argentina was extensive; about three-quarters of the samples were infected with diverse BF recombinants, near twenty percent had primary ART resistance and one sample presented a dual infection. Heterosexual transmission of genetically diverse, drug resistant strains among FSWs and their clients represents an important and underestimated threat, in Argentina.
Assuntos
Variação Genética , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/genética , Trabalho Sexual , Fármacos Anti-HIV/farmacologia , Argentina/epidemiologia , Farmacorresistência Viral/genética , Feminino , Genes env/genética , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Análise Heteroduplex , Humanos , Mutação , Filogenia , Prevalência , Recombinação Genética , Análise de Sequência de DNARESUMO
The prevalence, incidence, risk factors, and molecular genotyping of HIV-1 infection among men who have sex with men (MSM) were assessed through a prospective cohort study. The study was conducted in Buenos Aires from February 2003 to December 2004. Sociodemographic, sexual risk behavior data, and blood samples for HIV testing were collected at baseline and at 6 and 12 months. Cox regression analysis was applied to determine risk factors associated with HIV seroconversion. HIV-positive samples were analyzed by partial (pro/RT) and full-length genome sequencing. Of 811 HIV-negative participants evaluated at baseline, 327 volunteers that fulfilled the inclusion criteria were enrolled. Retention rates at 6 and 12 months were 97.2% and 91.5%, respectively. Twelve MSM seroconverted for HIV infection [incidence rate = 3.9 (95% CI = 2.0-6.7) per 100 person-years]. HIV seroconversion was associated with a greater number of different sexual contacts in the preceding 6 months (> or =10, hazard ratio = 3.3, 95% CI: 1.1-10.4). By partial pro/RT genotyping analysis, 83% HIV-positive samples were subtype B and 17% samples were BF recombinants, most of these being unique recombinant forms. This study describes for the first time the recruitment and follow-up of a cohort of MSM in Argentina. Retention rates and HIV incidence rate were high. These data should be considered as a promising potential population for HIV vaccine trials.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Adolescente , Adulto , Argentina/epidemiologia , Estudos de Coortes , Genótipo , HIV-1/isolamento & purificação , Homossexualidade Masculina , Humanos , Incidência , Masculino , Filogenia , Prevalência , Estudos Prospectivos , RNA Viral/genética , Fatores de Risco , Análise de Sequência de DNARESUMO
We describe the genetic diversity of currently transmitted strains of HIV-1 in men who have sex with men (MSM) in Buenos Aires, Argentina between 2000 and 2004. Nearly full-length sequence analysis of 10 samples showed that 6 were subtype B, 3 were BF recombinant and 1 was a triple recombinant of subtypes B, C and F. The 3 BF recombinants were 3 different unique recombinant forms. Full genome analysis of one strain that was subtype F when sequenced in pol was found to be a triple recombinant. Gag and pol were predominantly subtype F, while gp120 was subtype B; there were regions of subtype C interspersed throughout. The young man infected with this strain reported multiple sexual partners and sero-converted between May and November of 2004. This study reported for the first time the full genome analysis of a triple recombinant between subtypes B, C and F, that combines in one virus the three most common subtypes in South America.
Assuntos
HIV-1/classificação , HIV-1/genética , Recombinação Genética , Adulto , Argentina , Variação Genética , Genoma Viral , Infecções por HIV/virologia , Homossexualidade Masculina , Humanos , Masculino , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
To study the molecular epidemiology of human immunodeficiency virus (HIV) strains among men who have sex with men (MSM), the main high-risk group for HIV infection in Colombia, 113 HIV-positive MSM subjects recruited in Bogotá during the year 2002 were genotyped. By heteroduplex mobility assay (env HMA) all samples were classified as subtype B. Partial sequencing of the protease and the reverse transcriptase (Pro/RT) regions performed on a random subset of 10 samples revealed that nine were classified as subtype B, and one sample was subtype F. The specimen that is subtype F in pol and subtype B in env is likely to be is either a recombinant or a dual infection. In this study, we identify the HIV F subtype for the first time in Colombia.
Assuntos
Genes pol/genética , Infecções por HIV/genética , HIV-1/genética , Homossexualidade Masculina , Adolescente , Adulto , Colômbia/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Especificidade da EspécieRESUMO
To study the molecular epidemiology of human immunodeficiency virus type 1 (HIV-1) strains in Medellín, Colombia, 115 HIV-1-positive individuals who were recruited from an HIV outpatient hospital (Universitario San Vicente de Paul) during the period from July 2001 to January 2002 were genotyped. All samples were analyzed by envelope heteroduplex mobility assay and found to be subtype B. Twenty-four samples were randomly selected for sequencing of the protease and the reverse transcriptase regions; all isolates were found to be subtype B. Phylogenetic analysis of seven nearly full-length genomes showed that all samples were subtype B. This study shows that the HIV epidemic in Colombia continues to be dominated by the subtype B virus. The predominance of subtype B genotypes of HIV-1 strains in Medellín resembles what is seen in the nearby countries of Peru, Ecuador, and Venezuela.
Assuntos
Infecções por HIV/epidemiologia , HIV-1/classificação , Adolescente , Adulto , Colômbia/epidemiologia , Primers do DNA , DNA Viral/análise , Feminino , Genótipo , Infecções por HIV/etiologia , HIV-1/genética , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
A cohort study involving 60 human immunodeficiency virus (HIV)-negative male transvestite commercial sex workers (CSWs) was conducted in Montevideo, Uruguay in 1999-2001. Serum samples were tested for HIV by an enzyme-linked immunosorbent assay screening with immunoblot confirmation. Six participants seroconverted for an incidence-density rate of 6.03 (95% confidence interval = 2.21-13.12) per 100 person-years. Inconsistent condom use during client sex (adjusted hazard ratio [AHR] = 6.7), during oral sex (AHR = 5.6), and at the last sexual encounter (AHR = 7.8), and use of marihuana (AHR = 5.4) were marginally associated with HIV seroconversion. Five samples were genotyped in the protease and reverse transcriptase regions; three were subtypes B and two were BF recombinants. Full genome analysis of four samples confirmed all three subtype B samples and one of the two BF recombinants. Male transvestite CSWs sustained a high rate of HIV infection. Larger prospective studies are required to better define subtypes and associated sexual and drug-related risk factors.