Hepatitis C Among People Who Inject Drugs (PWID) in Latin America and the Caribbean: A Meta-Analysis of Prevalence Over Three Decades.

OBJECTIVE: People who inject drugs (PWID) are known to be more susceptible to infections such as hepatitis C virus (HCV). This systematic review and meta-analysis aimed to estimate the prevalence of hepatitis C among PWID in Latin America and the Caribbean (LAC). METHOD: The MEDLINE, Embase, and LILACS databases were searched without language restriction from inception to 2021. Articles were screened based on titles and abstracts. After reading the full texts, the articles were selected based on eligibility criteria. RESULTS: Of the 486 identified publications, 123 full texts were assessed, and 23 studies with a mean quality score of 7.2 were included. A total of 11,419 PWID were included in the meta-analysis, and the estimated overall prevalence of hepatitis C among PWID in LAC was 57.0%, which was higher than the United Nations Office on Drugs and Crime global prevalence of 50.2%. In meta-analyses of subgroups divided according to the risk of exposure to HCV infection (in addition to the imminent risk of injected drugs), the estimated prevalence of hepatitis C in PWID in the lowerrisk population (general) was 57.0%. The prevalence of hepatitis C in PWID who were infected with HIV was 61.0%. The estimated hepatitis C prevalence was also assessed for three periods: in 1991-2000, it was 59.0%; in 2001-2010, it was 63.0%; and in 2011-2020, it was 48.0%. CONCLUSIONS: The high estimated prevalence of hepatitis C in LAC reinforces the need for increased diagnostic efforts, strategies for treating drug addiction and hepatitis C, and harm reduction policies that target PWID.

Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis.

BACKGROUND: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. OBJECTIVE: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. METHODS: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. RESULTS: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. CONCLUSION: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.

Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis

Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.

Study of CXCL9-11 gene polymorphisms in liver fibrosis among patients with chronic hepatitis C.

Several factors are associated with the progression of chronic hepatitis C: comorbidities, lifestyle, and pathogenic factors, including immune response, apoptosis and heredity. Single nucleotide polymorphisms (SNPs) in the PNPLA3 and TM6SF2 genes are more widely studied genetic risk factors, while CXCL9-11 chemokines produced by hepatocytes in the process of infection are less well studied. Our aim was to evaluate the influence of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 in liver fibrosis when analysed together with PNPLA3 rs738409 and TM6SF2 rs58542926. The study included 219 patients with chronic hepatitis C. SNP genotyping was performed by real-time PCR. Univariate and multivariate analyses were used to detect the association between SNPs and advanced fibrosis in a recessive genetic model. All SNPs had a minimum allele frequency >5%, and CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 were in high linkage disequilibrium (D' ≥ 0.84). In the multivariate analysis, we observed that male gender (P = 0.000), older age (P = 0.025), moderate to intense inflammatory activity (P = 0.002), moderate to accentuated hepatic steatosis (P = 0.026) and the CT genotype of the TM6SF2 rs58542926 SNP (P = 0.014) presented significant associations with advanced fibrosis. Overall, the CXCL9 rs10336, CXCL10 rs3921, CXCL11 rs4619915 and PNPLA3 rs738409 SNPs did not influence liver fibrosis among patients with chronic hepatitis C.

The influence of gene-chronic hepatitis C virus infection on hepatic fibrosis and steatosis.

Host single nucleotide polymorphisms (SNPs) in different genes can play a role in chronic hepatitis C virus (HCV) infection and influence the presence of hepatic fibrosis and comorbidities such as hepatic steatosis. We assessed the combined effect of SNPs in the PNPLA3, MTTP, TM6SF2, and IFNL3/IFNL4 genes in 288 Brazilian patients who were chronically infected with HCV. Hepatic fibrosis was observed in 246 (85.4%) patients and hepatic steatosis in 141 (49.0%) patients. PNPLA3 rs738409 (CG/GG) (P = 0.044) and TM6SF2 rs58542926 (CT) (P = 0.004) were alone associated with fibrosis, and PNPLA3 rs738409 (P < 0.05, in distinct genetic models) was associated with steatosis. Multiple logistic regression of each SNP combined with HCV genotype 3 infection showed that MTTP rs1800591 (GT/TT) combined with HCV genotype 3 was associated with a 6.72-fold increased chance of hepatic steatosis (P = 0.013). In the analysis of SNPs combined 2 by 2, no influence on hepatic fibrosis or steatosis was observed.

Meta-Analysis of the Prevalence of HBV Infection Among Alcohol Users Worldwide.

AIMS: To investigate the prevalence of hepatitis B virus (HBV) infection among alcohol users. METHODS: A systematic search of articles in the PubMed, Web of Science and EMBASE databases was conducted. The methodological quality of each study was scored, and a meta-analysis was performed taking into account the heterogeneity expected among the studies. Publication bias was assessed using Begg's and Egger's tests. RESULTS: The search identified 998 reports that yielded 18 eligible studies. The studies comprised 12,204 alcohol users, who were mostly men. The mean score on the quality evaluation was 6.9, and 11 studies were classified as having a low risk of bias. The estimated worldwide prevalence of HBV was 20.0% (95%CI: 19.0-20.0). The heterogeneity among the studies was substantial (I2 = 96.7%). In subgroup analyses, it was observed that among alcohol user dependents with no description of liver damage, alcohol users with different stages of chronic liver disease and alcohol users who all had cirrhosis, the estimated prevalence was 10.0% (95%CI: 8.0-14.0), 14.0% (95%CI: 13.0-15.0) and 32.0% (95%CI: 29.0-35.0), respectively. The meta-regression analysis showed that the study quality score had an influence on the investigated prevalence (P = 0.005). Nevertheless, the funnel plot showed asymmetry, and there was evidence of publication bias according to Egger's test (P = 0.003) but not Begg's test (P = 0.869). CONCLUSIONS: The prevalence of HBV among alcohol users was high. HBV infection and alcohol consumption are factors affecting the development and worsening of liver disease; therefore, we suggest that adult alcohol users should be carefully monitored.

MTTP polymorphisms and hepatic steatosis in individuals chronically infected with hepatitis C virus.

Polymorphisms in the microsomal triglyceride transfer protein (MTTP) gene were genotyped in individuals who were chronically infected with hepatitis C virus (HCV). In the 236 patients, the frequencies of risk alleles of the -164T/C (rs1800804), -400A/T (rs1800803) and H297Q (rs2306985) polymorphisms were 0.30, 0.41 and 0.50, respectively. A significant association between the risk alleles of the -164T/C and -400A/T polymorphisms combined with HCV genotype 3 infection and the occurrence of steatosis was detected (p = 0.004 and p = 0.032), suggesting that a combination of host and viral factors can potentially be used to predict hepatic steatosis.

Genetic variation in the microsomal triglyceride transfer protein (-493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus.

BACKGROUND: In chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV). METHODS: Two hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G/T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses. RESULTS: The most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G/T SNP in patients infected with HCV genotype 3 (P < 0.001). CONCLUSIONS: In chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels.

Seroprevalence of hepatitis C virus among people living with HIV/AIDS in Latin America and the Caribbean: a systematic review.

BACKGROUND: Studies have shown that the immunosuppression induced by the human immunodeficiency virus (HIV) accelerates the natural history of liver disease associated with hepatitis C virus (HCV), with 3- to 5-fold higher odds of coinfected individuals developing cirrhosis. However, estimates of the seroprevalence of hepatitis C among people living with HIV/acquired immune deficiency syndrome (AIDS) (PLHA) in Latin America and the Caribbean (LAC) are widely variable. METHODS: We performed a systematic review to estimate the seroprevalence of HCV among PLHA. We searched studies on HIV and HCV infections in LAC included in the PubMed, LILACS and Embase databases in December of 2014 with no time or language restrictions. The following combinations of search terms were used in the PubMed and Embase databases: (HIV OR Acquired Immunodeficiency Syndrome Virus OR AIDS OR HTLV OR Human Immunodeficiency Virus OR Human T Cell) AND (HCV OR HEPATITIS C OR HEPATITIS C VIRUS OR HEPACIVIRUS) AND (name of an individual country or territory in LAC). The following search terms were used in the LILACS database: (HIV OR AIDS OR Virus da Imunodeficiencia Humana) AND (HCV OR Hepatite C OR Hepacivirus). An additional 11 studies were identified through manual searches. A total of 2,380 publications were located, including 617 duplicates; the remaining articles were reviewed to select studies for inclusion in this study. RESULTS: A total of 37 studies were selected for systematic review, including 23 from Brazil, 5 from Argentina, 3 from Cuba, 1 from Puerto Rico, 1 from Chile, 1 from Colombia, 1 from Mexico, 1 from Peru and 1 from Venezuela. The estimated seroprevalence of HCV infection varied from 0.8 to 58.5 % (mean 17.37; median 10.91), with the highest in Argentina and Brazil and the lowest in Venezuela and Colombia. CONCLUSIONS: Investigation of HCV infection among PLHA and of HIV infection among people living with HCV is highly recommended because it allows for better follow up, counseling and treatment of HIV/HCV-coinfected patients. Future studies with larger sample sizes are needed in both South and Central America to understand and address the risk factors associated with the acquisition of infection.

Prevalence of hepatitis C virus in Brazil's inmate population: a systematic review.

OBJECTIVE To estimate the prevalence of hepatitis C virus infection in Brazil's inmate population. METHODS Systematic review on hepatitis C virus infection in the inmate population. Brazilian studies published from January 1, 1989 to February 20, 2014 were evaluated. The methodological quality of the studies was assessed using a scale of 0 to 8 points. RESULTS Eleven eligible studies were analyzed and provided data on hepatitis C virus infection among 4,375 inmates from seven states of Brazil, with a mean quality classification of 7.4. The overall hepatitis C virus prevalence among Brazilian inmates was 13.6% (ranging from 1.0% to 41.0%, depending on the study). The chances of inmates being seropositive for hepatitis C virus in the states of Minas Gerais (MG), Sergipe (SE), Mato Grosso do Sul (MS), Rio Grande do Sul (RS), Goiás (GO) and Espirito Santo (ES) were 84.0% (95%CI 0.06;0.45), 92.0% (95%CI 0.04;0.13), 88.0% (95%CI 0.09;0.18), 74.0% (95%CI 0.16;0.42), 84.0% (95%CI 0.08;0.31) and 89.0% (95%CI 0.01;0.05) respectively, lower than that observed in the Sao Paulo state (seroprevalence of 29.3%). The four studies conducted in the city of Sao Paulo revealed a lower prevalence in more recent studies compared to older ones. CONCLUSIONS The highest prevalence of hepatitis C virus infection in Brazil's inmate population was found in Sao Paulo, which may reflect the urban diversity of the country. Despite Brazilian studies having good methodological quality to evaluate the prevalence of the hepatitis C virus, they are scarce and lack data on risk factors associated with this infection, which could support decisions on prevention and implementation of public health policies for Brazilian prisons.

Short Communication: Current Prevalence and Risk Factors Associated with Human T Lymphotropic Virus Type 1 and Human T Lymphotropic Virus Type 2 Infections Among HIV/AIDS Patients in São Paulo, Brazil.

During the 1990s, high prevalences of HIV/human T lymphotropic virus type 1 (HTLV-1) and HIV/human T lymphotropic virus type 2 (HTLV-2) coinfections were detected in São Paulo, Brazil in association with intravenous drug use (IDU). The current prevalences and risk factors for HIV/HTLV-1/-2 were evaluated in 1,608 patients attending the AIDS/STD Reference and Training Center in São Paulo. Blood samples were analyzed for HTLV-1/2-specific antibodies using enzyme immunoassays (EIA Murex HTLV-I+II, Diasorin, and Gold ELISA HTLV-I+II, REM) and immunoblotting (HTLV Blot 2.4, MP Biomedicals and INNO-LIA HTLV-I/II, Innogenetics) and for the pol proviral DNA segments of HTLV-1 and HTLV-2 by "in-house" real-time PCR. These analyses revealed that 50 (3.11%) of the samples were HTLV positive, including 25 (1.55%) that were HTLV-1 positive, 21 (1.31%) that were HTLV-2 positive, and 4 (0.25%) that were HTLV positive (untypeable). The median age of the HIV/HTLV-coinfected individuals was 50 years versus 44 years in the overall population (p=0.000). The risk factors associated with HIV/HTLV-1/-2 coinfections were female gender (OR 3.26, 1.78-5.95), black/pardo color (OR 2.21, 1.21-4.03), infection with hepatitis B virus (HBV) (OR 4.27, 2.32-7.87) or hepatitis C virus (HCV) (OR 24.40, 12.51-48.11), and intravenous drug use (IDU) (OR 30.01, 15.21-59.29). The current low prevalence of HTLV-1/2 in HIV-infected patients in São Paulo could be explained in part by programs providing IDUs with sterile needles and syringes and changes in the drug usage patterns of individuals from injecting cocaine to smoking crack cocaine.

Prevalence of hepatitis C virus in Brazil's inmate population: a systematic review / Prevalência do vírus da hepatite C na população carcerária do Brasil: revisão sistemática

OBJECTIVE To estimate the prevalence of hepatitis C virus infection in Brazil's inmate population.METHODS Systematic review on hepatitis C virus infection in the inmate population. Brazilian studies published from January 1, 1989 to February 20, 2014 were evaluated. The methodological quality of the studies was assessed using a scale of 0 to 8 points.RESULTS Eleven eligible studies were analyzed and provided data on hepatitis C virus infection among 4,375 inmates from seven states of Brazil, with a mean quality classification of 7.4. The overall hepatitis C virus prevalence among Brazilian inmates was 13.6% (ranging from 1.0% to 41.0%, depending on the study). The chances of inmates being seropositive for hepatitis C virus in the states of Minas Gerais (MG), Sergipe (SE), Mato Grosso do Sul (MS), Rio Grande do Sul (RS), Goiás (GO) and Espirito Santo (ES) were 84.0% (95%CI 0.06;0.45), 92.0% (95%CI 0.04;0.13), 88.0% (95%CI 0.09;0.18), 74.0% (95%CI 0.16;0.42), 84.0% (95%CI 0.08;0.31) and 89.0% (95%CI 0.01;0.05) respectively, lower than that observed in the Sao Paulo state (seroprevalence of 29.3%). The four studies conducted in the city of Sao Paulo revealed a lower prevalence in more recent studies compared to older ones.CONCLUSIONS The highest prevalence of hepatitis C virus infection in Brazil's inmate population was found in Sao Paulo, which may reflect the urban diversity of the country. Despite Brazilian studies having good methodological quality to evaluate the prevalence of the hepatitis C virus, they are scarce and lack data on risk factors associated with this infection, which could support decisions on prevention and implementation of public health policies for Brazilian prisons.

RESUMOOBJETIVO Estimar prevalência de infecção pelo vírus da hepatite C entre a população carcerária no Brasil.MÉTODOS Revisão sistemática sobre infecção pelo vírus da hepatite C em populações carcerárias. Foram avaliados estudos brasileiros publicados a partir de 1 de janeiro de 1989 até 20 de fevereiro de 2014. A qualidade metodológica dos estudos foi avaliada utilizando-se escala de zero a oito pontos.RESULTADOS Onze estudos elegíveis foram analisados, os quais forneceram dados sobre a infecção pelo vírus da hepatite C de 4.375 detentos de sete estados do Brasil, com classificação em média de qualidade de 7,4. A prevalência de infecção pelo vírus da hepatite C na população carcerária brasileira foi 13,6%, (variando de 1,0% a 41,0%, dependendo do estudo). As chances de os indivíduos serem soropositivos para o vírus da hepatite C nos estados de Minas Gerais, Sergipe, Mato Grosso do Sul, Rio Grande do Sul, Goiás e Espírito Santo foram 84,0% (IC95% 0,06;0,45), 92,0% (IC95% 0,04;0,13), 88,0% (IC95% 0,09;0,18), 74% (IC95% 0,16;0,42), 84,0% (IC95% 0,08;0,31) e 89,0% (IC95% 0,01;0,05), respectivamente, inferiores àquela observada no estado de São Paulo (soroprevalência de 29,3%). Os quatro estudos realizados na cidade de São Paulo mostraram menor prevalência em estudos mais recentes em comparação aos mais antigos.CONCLUSÕES A maior prevalência de infecção pelo vírus da hepatite C em população carcerária do Brasil foi encontrada em São Paulo, o que pode refletir a diversidade urbana do País. Apesar de os estudos brasileiros apresentarem boa qualidade metodológica para avaliação da prevalência do vírus da hepatite C, são escassos e faltam dados sobre fatores de risco associados a esta infecção, dados esses que poderiam auxiliar nas decisões de prevenção e implementação de políticas em saúde pública para as prisões brasileiras.

Comparação de testes laboratoriais para o diagnóstico de infecção por vírus linfotrópicos de células T humanas do tipo 1 (HTLV-1)e tipo 2 (HTLV-2) em pacientes infectados por HIV-1 / Comparison of laboratorial tests for the diagnosis of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) in HIV-1 infected patients

O presente estudo pesquisou o melhor algoritmo de testes laboratoriais para efetuar o diagnóstico de infecção por vírus linfotrópicos de células T humanas dos tipos 1 (HTLV-1) e 2 (HTLV-2) em pacientes HIV-1 positivos. Amostras de sangue de 1.608 pacientes do CRT DST/Aids-SP foram analisadas quanto à presença de anticorpos específicos usando-se dois ensaios de triagem (EIA Murex HTLV-I+II e Gold ELISA HTLV-I/II), dois confirmatórios [HTLV Blot 2.4 (Western Blot – WB) e INNO-LIA HTLV I/II (Line ImmunoAssay - LIA)] e um molecular (PCR em tempo real pol). Na triagem foram detectados 51(Murex) e 49 (Gold ELISA) soros reagentes. Pelo WB, 23 soros confirmaram infecção por HTLV-1, 12 HTLV-2, seis HTLV e nove apresentaram perfis indeterminados. O LIA detectou 24 soros HTLV-1 positivos, 20 HTLV-2 e seis HTLV. A PCR evidenciou segmento pol de HTLV-1 em 18 e HTLV-2 em 12 amostras de sangue. Pelos testes confirmatórios, em 50 pacientes foi confirmada a infecção por HTLV: 25 HTLV-1 (1,55 %), 21 HTLV-2 (1,31 %) e quatro HTLV (0,25 %). As sensibilidades do LIA, WB e PCR foram de 96 %, 76 % e 60 %, respectivamente. Considerando-se apenas o custo, o melhor algoritmo diagnóstico para população infectada pelo HIV-1 foi o uso da PCR seguida do LIA...

Inability to detect human T cell lymphotropic virus type 2-specific antibodies in a patient coinfected with HIV-1, human T cell lymphotropic virus type 1, human T cell lymphotropic virus type 2, and hepatitis C virus.

HIV-1, human T cell lymphotropic virus type 1 and type 2 (HTLV-1 and HTLV-2) and hepatitis C virus (HCV) are common among intravenous drug users (IDUs) and can cause chronic infections in the host. Usually, the diagnosis of such viruses employs serological assays; however, some difficulties in confirming HTLV-2 infection have been reported in high-risk populations in Brazil. We present data of an unusual case of coinfection with HIV-1, HTLV-1, HTLV-2, and HCV in a male IDU in which HTLV-2 was detected only by molecular assays. Comparative analysis of retroviruses from 2002 and 2012 showed identical HTLV-1 and HTLV-2 sequences (LTR, env, and tax), and a change in HIV-1 tropism from CXCR4 to CCR5. No mutation was detected in the hot points of the env region of the HTLV-2 isolate that justified the lack of rgp46-II-specific antibodies. These data emphasize the need for molecular assays to diagnose HTLV-2 in high-risk populations in Brazil.

Human T cell lymphotropic virus type 2a strains among HIV type 1-coinfected patients from Brazil have originated mostly from Brazilian Amerindians.

The human T cell lymphotropic virus type 2 (HTLV-2) is found mainly in Amerindians and in intravenous drug users (IDUs) from urban areas of the United States, Europe, and Latin America. Worldwide, HTLV-2a and HTLV-2b subtypes are the most prevalent. Phylogenetic analysis of HTLV-2 isolates from Brazil showed the HTLV-2a subtype, variant -2c, which spread from Indians to the general population and IDUs. The present study searched for the types of HTLV-2 that predominate among HIV-1-coinfected patients from southern and southeastern Brazil. Molecular characterization of the LTR, env, and tax regions of 38 isolates confirmed the HTLV-2c variant in 37 patients, and one HTLV-2b in a patient from Paraguay. Phylogenetic analysis of sequences showed different clades of HTLV-2 associated with risk factors and geographic region. These clades could represent different routes of virus transmission and/or little diverse evolutionary rates of virus. Taking into account the results obtained in the present study and the lack of the prototypic North American HTLV-2a strain and HTLV-2b subtypes commonly detected among HIV-coinfected individuals worldwide, we could speculate on the introduction of Brazilian HTLV-2 strains in such populations before the introduction of HIV.

Vírus linfotrópicos de células T humanas dos tipos 1 e 2 (HTLV-1 e HTLV-2): estudo de segmentos do genoma proviral obtidos de pacientes com HIV/Aids de São Paulo e de Londrina e região / Human T-lymphotropic virus type 1 and 2 (HTLV-1 and HTLV-2): study on proviral genome segments obtained from patients with HIV/Aids from Sao Paulo and Londrina and vicinities

O Brasil é considerado o país com o maior número absoluto de indivíduos infectados pelos vírus linfotrópicos de células T humanas dos tipos 1 e 2 (HTLV-1 e HTLV2), perto de 2,5 milhões; além disso, é também considerado epidêmico para o HIV e, portanto, casos de coinfecção HIV/HTLV são frequentes no país. O presente trabalho efetuou o seqüenciamento das regiões LTR, env e tax do genoma proviral do HTLV-1 e do HTLV-2 isolados das amostras de sangue de pacientes coinfectados pelo HIV-1 de Londrina e região (n=34) e de São Paulo (n=20), para realizar a caracterização molecular e determinar subtipos virais. Foram utilizadas na análise das sequências as ferramentas Sequencher 4.7, BLAST, Genotyping-NCBI, Subtyping-REGA, BioEdit 7.0.5.3, ClustalW, GenBank, PAUP 4.0.b10, Modeltest 3.7, TreeView 1.6.6 e MEGA4. As diversas análises confirmaram como subtipos prevalentes o HTLV-1a, subgrupo Transcontinental A, e o HTLV-2a (variante -2c). Foram detectadas assinaturas moleculares nos isolados do Brasil. Detectou-se o genótipo brasileiro taxA para o HTLV-1 e para o HTLV-2 a Tax longa, a qual é característica da variante HTLV-2c. Houve também a confirmação da troca de aminoácido S1909P no env dos HTLV-2. Especulou-se sobre duas entradas do HTLV-1 no Brasil e sobre a disseminação do HTLV-2c em grupos distintos quanto ao comportamento de risco e região geográfica. O estabelecimento de métodos laboratoriais otimizados para isolados brasileiros de HTLV-1 e HTLV-2 possibilitou melhor compreensão da diversidade genômica e da origem e disseminação dos HTLVs em populações coinfectadas pelo HIV no Brasil

Brazil is considered the country with the major absolute number of individuals infected with human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2), close to 2,500,000; moreover, it is also considered epidemic for HIV/Aids =and therefore HIV/HTLV coinfection is frequent in the country. This study aimed at sequencing the LTR, env and tax regions of the proviral genome of HTLV-1 and HTLV-2 isolated from blood samples obtained from patients coinfected with HIV-1 from Londrina and vicinities (n=34) and São Paulo (n=20), in order to perform the molecular characterization and viral subtyping. For sequences analysis, several bioinformatics tools were employed: Sequencher 4.7, BLAST, Genotyping-NCBI, Subtyping-REGA, BioEdit 7.0.5.3, ClustalW, GenBank, PAUP 4.0.b10, Modeltest 3.7, TreeView 1.6.6 and MEGA4. The results confirmed as prevalent the HTLV-1a subtype, the Transcontinental subgroup A, and the HTLV-2a (variant-2c). Molecular signatures characteristic of Brazilian isolates were detected: taxA Brazilian genotype in HTLV-1, and the long Tax which is characteristic of the HTLV-2c in HTLV-2. Also, it was confirmed the S1909P amino acid change in the env region of HTLV-2c. It was speculated on two entrances of HTLV-1 in Brazil, and on the spread of HTLV-2c in distinct groups related to risk factors and geographic region. The establishment and optimization of laboratory methods performed in this study allowed to get a better understanding on HTLVs genomic diversity, and to give insights on the origin and spread of HTLVs in populations coinfected with HIV in Brazil

LTR point mutations in the Tax-responsive elements of HTLV-1 isolates from HIV/HTLV-1-coinfected patients.

BACKGROUND: In Virology Journal 2011, 8:535, Neto et al. described point mutations into Tax-responsive elements (TRE) of the LTR region of HTLV-1 isolates from asymptomatic carriers from Sao Paulo, Brazil, and hypothesized that the presence of the G232A mutation in the TRE-1 increase viral proliferation and consequently the proviral load (PvL), while the A184G mutation in the TRE-2 do not have such effect. FINDINGS: We performed the real-time PCR assay (pol) and sequenced LTR region of HTLV-1 isolates from 24 HIV/HTLV-1-coinfected patients without HTLV-1-associated diseases from the same geographic area. These sequences were classified as belonging to the transcontinental subgroup A of the Cosmopolitan subtype a. The frequency of G232A mutation (16/24, 66.7%) was high as much as 61.8% reported by Neto's in HTLV-1 asymptomatic carriers with high PvL. High frequency (13/24, 54.2%) of double mutations G232A and A184G was also detected in HIV/HTLV-1-coinfected patients. We did not quantify PvL, but comparative analyses of the cycle threshold (Ct) median values of the group of isolates presenting the mutated-types sequences (Ct 33.5, n = 16) versus the group of isolates with the wild-type sequences (Ct 32, n = 8) showed no statistical difference (p = 0.4220). CONCLUSION: The frequencies of mutated-type sequences in the TRE-1 and TRE-2 motifs were high in HIV/HTLV-1-coinfected patients from Sao Paulo, Brazil. If these LTR point mutations have predictive value for the development of HTLV-1-associated diseases or they correspond to the subtype of virus that circulate in this geographic area has to be determined.

Tax gene characterization of human T-lymphotropic virus type 1 strains from Brazilian HIV-coinfected patients.

The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil.

Phylogenetic and similarity analysis of HTLV-1 isolates from HIV-coinfected patients from the south and southeast regions of Brazil.

HTLV-1 is endemic in Brazil and HIV/HTLV-1 coinfection has been detected, mostly in the northeast region. Cosmopolitan HTLV-1a is the main subtype that circulates in Brazil. This study characterized 17 HTLV-1 isolates from HIV coinfected patients of southern (n=7) and southeastern (n=10) Brazil. HTLV-1 provirus DNA was amplified by nested PCR (env and LTR) and sequenced. Env sequences (705 bp) from 15 isolates and LTR sequences (731 bp) from 17 isolates showed 99.5% and 98.8% similarity among sequences, respectively. Comparing these sequences with ATK (HTLV-1a) and Mel5 (HTLV-1c) prototypes, similarities of 99% and 97.4%, respectively, for env and LTR with ATK, and 91.6% and 90.3% with Mel5, were detected. Phylogenetic analysis showed that all sequences belonged to the transcontinental subgroup A of the Cosmopolitan subtype, clustering in two Latin American clusters.