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We evaluated vertical transmission and linkage to care in women with HCV and history of injection drug use employing co-localized testing and treatment. Transmission occurred in 1 of 23 infants, with mother-infant genetic distance of 1.26%. Rates for infant testing, maternal linkage and cure were 77%, 52%, and 100%, respectively.
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BK polyomavirus (BKPyV) infection is common after hematopoietic stem cell transplantation (HSCT) and is associated with the development of hemorrhagic cystitis (HC). The role that BKPyV plays in the pathogenesis of HC is not well characterized. We investigated the impact of BKPyV diversity on the development of HC using a previously established cohort of pediatric HSCT patients. There were 147 urine samples with quantifiable BKPyV at month 1 after HSCT; 137 (93.2%) were amplified using our in-house polymerase chain reaction approach and sent for next-generation sequencing. Subtype Ia was most frequent (61.3%), followed by subtype Ib1 (31.4%). The median viral load of subtype Ia samples was higher than for subtype Ib1 at month 1. Across the protein coding regions, APOBEC-induced mutations and signature patterns associated with HC were identified. This is the largest sequencing study of a single cohort of HSCT patients, providing a vast resource of sequence data for future analyses.
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Vírus BK , Cistite , Transplante de Células-Tronco Hematopoéticas , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Criança , Vírus BK/genética , Hemorragia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
INTRODUCTION: Hepatitis C virus (HCV) genotype 5 was originally identified in South Africa, where it represents 35-60% of all HCV infections. There are limited data on resistance-associated variants (RAVs) in South Africa. Thus, we investigated variability within the NS3/NS4A, NS5A, and NS5B genes of treatment-naïve individuals with HCV genotype 5 infection at the Dr. George Mukhari Academic Hospital (DGMAH) in Pretoria, South Africa. METHODS: Nested PCR was performed to amplify the NS3/4A, NS5A, and NS5B genes. RAVs were evaluated using the Geno2pheno tool. RESULTS: In the NS3/4A gene, F56S and T122A were detected in one sample each. The D168E mutation was detected in 7 samples. Within the NS5A gene, the T62M mutation was detected in 2 individuals. In the NS5B gene, 8 of 12 individuals (67%) had the A421V mutation, while all 12 individuals (100%) had the S486A mutation. DISCUSSION: RAVs were detected frequently among treatment-naïve individuals with HCV genotype 5 infection in South Africa. Thus, resistance testing may be prudent when initiating treatment of patients with genotype 5 infection. Additional population-based studies are needed to understand the prevalence of these RAVs during HCV genotype 5 infection.
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Hepatite C Crônica , Hepatite C , Humanos , Hepacivirus/genética , Antivirais/farmacologia , África do Sul/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C/epidemiologia , Genótipo , Farmacorresistência Viral/genética , Proteínas não Estruturais Virais/genéticaRESUMO
The human pegivirus type 1 (HPgV-1)-as known as hepatitis G virus and GB virus C-is a common single-stranded RNA flavivirus. Because few studies have demonstrated an association between HPgV-1 infection and disease, screening for HPgV-1 is not performed routinely. Nonetheless, a beneficial impact of HPgV-1 infection on HIV disease progression has been reported in multiple studies. Given the burden of HIV in Asia and the complex interactions between viral co-infections and the host, we provide a comprehensive overview of the existing data from Asia on HPgV-1 infection, including the prevalence and circulating genotypes in all Asian countries with data reported. This review highlights the research conducted thus far and emphasizes the need for additional studies on HPgV-1 across the Asian continent.
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Coinfecção , Infecções por Flaviviridae , Vírus GB C , Infecções por HIV , Hepatite Viral Humana , Ásia/epidemiologia , Coinfecção/epidemiologia , Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/epidemiologia , Vírus GB C/genética , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Filogenia , RNA Viral/genéticaRESUMO
The US is experiencing a major public health crisis that is fueled by the illicit use of synthetic opioids including fentanyl. While several drugs of abuse can enhance viral replication and/or antagonize immune responses, the impact of specific synthetic opioids on HIV pathogenesis is poorly understood. Thus, we evaluated the effects of fentanyl on HIV replication in vitro. HIV-susceptible or HIV-expressing cell lines were incubated with fentanyl. HIV p24 synthesis and chemokine receptor levels were quantified by ELISA in culture supernatants and cell lysates, respectively. Addition of fentanyl resulted in a dose-dependent increase in HIV replication. Fentanyl enhanced expression of the HIV chemokine co-receptors CXCR4 and CCR5 and caused a dose-dependent decrease in cell viability. The opioid antagonist naltrexone blocked the effect of fentanyl on HIV replication and CCR5 receptor levels but not CXCR4 receptor levels. TLR9 expression was induced by HIV; however, fentanyl inhibited TLR9 expression in a dose-dependent manner. These data demonstrate that the synthetic opioid fentanyl can promote HIV replication in vitro. As increased HIV levels are associated with accelerated disease progression and higher likelihood of transmission, additional research is required to enhance the understanding of opioid-virus interactions and to develop new and/or optimized treatment strategies for persons with HIV and opioid use disorder.
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Infecções por HIV , HIV-1 , Humanos , Fentanila/farmacologia , Fentanila/metabolismo , Analgésicos Opioides/farmacologia , Analgésicos Opioides/metabolismo , Receptores de Quimiocinas/metabolismo , Receptor Toll-Like 9 , HIV-1/fisiologia , Quimiocinas/metabolismo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Replicação ViralRESUMO
Occult hepatitis B virus (OBI) infection is defined by the presence of viral DNA in the liver and/or serum in absence of hepatitis B surface antigen (HBsAg). While multiple studies have identified mutations that are associated with OBI, only a small portion of these mutations have been functionally characterized in vitro. Using complementary in silico approaches, the effects of OBI-associated amino acid mutations on HBV protein function in HBV/HIV-positive ART-naïve South Africans were evaluated. Two OBI-associated mutations in the PreS1 region, one in the PreS2 region, and seven in the surface region of subgenotype A1 sequences were identified as deleterious. In subgenotype A2 sequences, 11 OBI-associated mutations in the PreS1 region, seven in the PreS2 region, and 31 in the surface region were identified as deleterious. In the polymerase region, 14 OBI-associated mutations in subgenotype A1 and 71 OBI-associated mutations in subgenotype A2 were identified as deleterious. This study utilized in silico approaches to characterize the likely impact of OBI-associated mutations on viral function, thereby identifying and prioritizing candidates and reducing the significant cost associated with functional studies that are essential for mechanistic studies of the OBI phenotype.
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Vírus da Hepatite B/genética , Hepatite B/virologia , Mutação , Simulação por Computador , DNA Viral/sangue , Genótipo , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/química , Vírus da Hepatite B/patogenicidade , Humanos , África do SulRESUMO
BK polyomavirus (BKPyV or BKV) is a non-enveloped, circular double-stranded DNA virus that may exceed 80% seroprevalence in adults. BKV infection typically occurs during childhood, and the majority of adults are latently infected. While BKV infection is rarely associated with clinical disease in most individuals, in immunosuppressed individuals, reactivation may cause kidney (BK-associated nephropathy) or bladder (hemorrhagic cystitis and ureteral stenosis) injury. No antiviral therapies have been approved for the treatment of BKV infection. Reducing immunosuppression is the most effective therapy, although this is not feasible in many patients. Thus, a robust understanding of viral pathogenesis and viral diversity remains important for the development of future therapeutic strategies. Studies of BKV diversity are quite sparse compared to other common viral infections; thus, much of our understanding of BVK variability and evolution relies heavily analogous studies of other viruses such as HIV or viral hepatitis. We provide a comprehensive review of BKV diversity at the population and individual level with careful consideration of how viral variability may impact viral replication, pathogenesis, tropism, and protein function. We also discuss a number of outstanding questions related to BK virus diversity that should be explored rigorously in future studies.
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Vírus BK/classificação , Infecções por Polyomavirus/virologia , Animais , Vírus BK/genética , Biodiversidade , Evolução Molecular , Variação Genética , Genoma Viral , Genômica/métodos , Humanos , FilogeniaRESUMO
BACKGROUND: BK polyomavirus (BKPyV) is associated with symptomatic hemorrhagic cystitis after hematopoietic cell transplantation (HCT). Little is known about the host immune response, effectiveness of antiviral treatment, or impact of asymptomatic replication on long-term kidney function. METHODS: In children and young adults undergoing allogeneic HCT, we quantified BKPyV viruria and viremia (pre-HCT and at Months 1-4, 8, 12, and 24 post-HCT) and tested associations of peak viremia ≥10 000 or viruria ≥109 copies/mL with estimated kidney function (glomerular filtration rate, eGFR) and overall survival at 2 years posttransplant. We examined the factors associated with viral clearance by Month 4, including BKPyV-specific T cells by enzyme-linked immune absorbent spot at Month 3 and cidofovir use. RESULTS: We prospectively enrolled 193 participants (median age 10 years) and found that 18% had viremia ≥10 000 copies/mL and 45% had viruria ≥109 copies/mL in the first 3 months post-HCT. Among the 147 participants without cystitis (asymptomatic), 58 (40%) had any viremia. In the entire cohort and asymptomatic subset, having viremia ≥10 000 copies/mL was associated with a lower creatinine/cystatin C eGFR at 2 years post-HCT. Viremia ≥10 000 copies/mL was associated with a higher risk of death (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1-4.2). Clearing viremia was associated with detectable BKPyV-specific T cells and having viremia <10 000 copies/mL, but not cidofovir exposure. CONCLUSIONS: Screening for BKPyV viremia after HCT identifies asymptomatic patients at risk for kidney disease and reduced survival. These data suggest potential changes to clinical practice, including prospective monitoring for BKPyV viremia to test virus-specific T cells to prevent or treat BKPyV replication.
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Vírus BK , Transplante de Células-Tronco Hematopoéticas , Infecções por Polyomavirus , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunidade , Infecções por Polyomavirus/epidemiologia , Estudos Prospectivos , Transplante de Células-Tronco , Adulto JovemRESUMO
Hepatitis B virus (HBV) infects over 250 million people worldwide. Vaccination is effective at preventing infection, although several mutations within the "a" determinant region of the HBV surface antigen (HBsAg) are associated with vaccine escape. We evaluated the frequency, genotype, and global distribution of polymorphisms at sites associated with vaccine escape in 4244 unique full-length HBV genomes. The "a" determinant within the Surface gene was inspected for polymorphisms at sites identified previously associated with vaccine escape. Nearly, 268 (6.3%) sequences from 36 countries contained a polymorphism at a site associated with vaccine escape including 22 genotype A, 99 genotype B, 93 genotype C, 32 genotype D, 14 genotype E, 3 genotype F, 2 genotype G, and 3 genotype I. In genotype A, the most common polymorphism occurred at M133. In genotype B, Q129 and M133 occurred 45 and 51 times, respectively, accounting for 94% of polymorphisms. Polymorphisms at G145 were most frequent in genotype C, while P120 was most common in genotype D. Among all genotypes, polymorphisms at M133 were the most common and accounted for 30.9% of polymorphisms. Polymorphisms at T116, P120, F134, K141, and P142 occurred in geographically diverse locations, whereas polymorphisms at Q129, M133, D144, and G145 were concentrated in East Asia. While the sample size is large, this approach relied on convenience sampling within each country, and many countries have no data available, thereby highlighting the need for additional routine surveillance of surface antigen mutations associated with vaccine escape.
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BACKGROUND: Occult hepatitis B virus (HBV) - characterized by the absence of detectable HBsAg in the presence of HBV DNA - represents a potential threat for blood safety. OBJECTIVES: This study was conducted with the aim to investigate the serological and molecular characterization of occult HBV infection (OBI) among blood donors in Mozambique. METHODS: 1,502 blood donors were tested for HBsAg. All HBsAg-negative individuals were tested for HBV DNA. Antibodies against HBV core, surface and HBe antigen (anti-HBc, anti-HBs, HBeAg) were measured in HBV DNA positive individuals. FINDINGS: 1435 serum samples were HBsAg negative and 16 positive for HBV DNA, 14 confirmed to have OBI, corresponding to a frequency of 0.98%. Of the 14 OBI infections identified, 13/14 (92.8%) were positive for anti-HBc, 4/14 (28.5%) for anti-HBs, and no samples were reactive for HBeAg. Of the 14 OBI cases, nine samples (64.2%) were sequenced for the S/P region. Eight samples (88.9%) belonged to genotype A1 and one (11.1%) to genotype E. One escape mutation (T123A) associated with OBI and various amino acid substitutions for genotype A1 and E were observed. MAIN CONCLUSIONS: Our results show the importance of using nucleic acid amplification test to detect occult hepatitis B infection in blood donors in Mozambique.
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Doadores de Sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Adulto , Estudos Transversais , DNA Viral , Feminino , Humanos , Masculino , Moçambique , Filogenia , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: The C-C chemokine receptor Type 5 (CCR5) is a key receptor for human immunodeficiency virus type 1 (HIV-1) entry into T-cells and a variant allele, CCR5 delta-32, is associated with decreased viral replication and disease progression. Active HIV-1 replication is highly associated with accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a role in the development of hepatic fibrosis and evaluated the longitudinal effect of natural or drug-induced CCR5 mutation and blockade on biomarkers of liver fibrosis in HIV-1 patients. METHODS: To accomplish this goal, we examined 2 distinct cohorts. First, we evaluated fibrosis markers in the Multicenter Hemophilia Cohort Studies (MHCS), which included subjects with HIV and hepatitis C virus (HCV) coinfection with the CCR5 delta-32 allele. We also evaluated an HIV-1 infected cohort that was treated with a dual CCR5/CCR2 antagonist, cenicriviroc. The enhanced liver fibrosis (ELF) index was validated against liver histology obtained from HCV/HIV and HCV patients and demonstrated strong correlation with fibrosis stage. RESULTS: In both the MHCS patients and patients treated with cenicriviroc, CCR5 mutation or blockade was associated with a significant decrease in the ELF index. Among the patients with the delta-32 allele, the ELF index rate significantly decreased in sequential samples as compared to CCR5 wild-type patients (P = .043). This was not observed in control subjects treated with efavirenz nor with a lower dose of 100 mg cenicriviroc. CONCLUSION: These findings suggest that hepatic fibrosis in HIV-1 infected patients can be modulated by the mutation of CCR5 and/or use of CCR5/CCR2 blockade agents. CLINICAL TRIALS REGISTRATION: NCT01338883.
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Infecções por HIV/complicações , Hepatite C/complicações , Imidazóis/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/imunologia , Receptores CCR5/genética , Adolescente , Adulto , Idoso , Alelos , Biomarcadores/análise , Antagonistas dos Receptores CCR5/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Coinfecção/complicações , Coinfecção/virologia , Método Duplo-Cego , Infecções por HIV/tratamento farmacológico , HIV-1 , Hepacivirus , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Observacionais como Assunto , Sulfóxidos , Adulto JovemRESUMO
Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).
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Hepacivirus , Hepatite C/transmissão , Transplante de Fígado/efeitos adversos , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Seguimentos , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Incidência , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Reação em Cadeia da Polimerase , Estudos Prospectivos , Taxa de Sobrevida , Doadores de Tecidos/estatística & dados numéricos , Adulto JovemRESUMO
Hepatitis B virus (HBV) exhibits a high degree of heterogeneity with at least 10 genotypes (A-J) identified to date. Intergenotypic recombination is relatively common. Previously, we investigated HBV drug resistance in HIV/HBV co-infected individuals in Ghana. After identifying multiple circulating genotypes and a novel D/E recombinant, we sought to determine if additional individuals were also infected with recombinant HBV. Partial genome sequences from three individuals were initially identified as genotype A4. Full-length HBV genomes were obtained using rolling circle amplification followed by PCR and shown to cluster with known A/E recombinant viruses. Similar recombination breakpoints were observed in these three individuals suggesting local spread of this novel recombinant HBV in Ghana.
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Genótipo , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/virologia , Recombinação Genética , Adulto , Análise por Conglomerados , Feminino , Gana , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Sequenciamento Completo do GenomaRESUMO
Hepatitis B virus (HBV) poses a significant threat to blood transfusion safety in sub-Saharan Africa (SSA) where allogeneic blood donations are screened serologically, and more sensitive nucleic acid tests (NATs) are utilized infrequently. HBV strains circulating among blood donors in Botswana are not yet characterized. We designed a cross-sectional study to determine the HBV sub-genotypes and prevalence of hepatitis B surface antigen (HBsAg) among blood donors between November 2014 and October 2015. A total of 12,575 blood donations were screened for HBsAg and 50 consecutive plasma samples were selected for genotyping from confirmed HBsAg+ donations. Overlapping Pol and complete S (Pol/S) open reading frames (ORFs) were sequenced from extracted HBV DNA. To identify any signature amino acids, mutations were compared to sequences from a cohort of chronic HBV patients co-infected with HIV and were treatment naïve. The prevalence of HBsAg+ blood donors was 1.02% (95% CI 0.9-1.2%), and the circulating sub-genotypes were A1 serotype adw2 (36.1%), D2 serotype ayw2 (2.9%), and D3 serotypes ayw 1/2 (58.3%). Prevalence of escape mutations was 14% from HBV isolates of blood donors and 15% from isolates of HBV/HIV co-infected patients (p = 0.6926). The escape mutations sP120L, sG130R, sY134H, and sD144A were identified predominantly among HBV isolates from blood donors. These escape mutations have been associated with accelerated HBV sequelae [e.g., liver cirrhosis (LC) and hepatocellular carcinoma (HCC)], failure to detect HBsAg, inability to respond to immunoglobulin (Ig) therapy, and HBV vaccine escape. Characterizing the HBV burden, circulating sub-genotypes, and clinically relevant mutations among blood donors in Botswana is important to elucidate the efficacy of currently available vaccines, predicting HBV-transmission patterns, understanding the cohort's risk to HBV-related complications, and to developing prevention strategies and effective genotype-based antiretroviral therapies.
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Doadores de Sangue , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite B/virologia , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Botsuana/epidemiologia , Estudos Transversais , DNA Viral/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Reação em Cadeia da Polimerase , Vigilância da População , Prevalência , Sorogrupo , Adulto JovemRESUMO
Hepatitis C virus (HCV) is known to inhibit hepatitis B virus (HBV) replication in patients with HBV/HCV coinfection. Reactivation of HBV in patients treated for HCV with direct-acting agents (DAAs) has emerged recently as an important clinical consideration. A growing number of case reports and case series support the association between new HCV treatments and HBV reactivation. Yet, very little is known about the specific viral characteristics that facilitate reactivation as functional characterization of the reactivated HBV has been conducted only rarely. This review provides the most recent data on HBV reactivation in the context of DAA initiation and highlights the existing viral genomic data from reactivating viruses. Current functional studies of HBV reactivation are largely limited by the retrospective identification of cases, no standardization of genomic regions that are studied with respect to HBV reactivation, and the lack of inclusion of nonreactivating controls to establish specific viral mutations that are associated with HBV reactivation. Importantly, none of these sequencing studies included cases of HBV reactivation after initiation of DAAs. While new HCV treatments have revolutionized care for HCV infected patients, HBV reactivation will likely increase in frequency, as DAAs are more commonly prescribed. Pretreatment determination of HBV status and thoughtful management of HBV coinfections will be necessary and lead to improved patient safety and yield optimal treatment results.
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Coinfecção , Hepacivirus/fisiologia , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Hepatite C/virologia , Interações Microbianas , Ativação Viral , Antivirais/farmacologia , Antivirais/uso terapêutico , Genoma Viral , Genótipo , Hepatite B/tratamento farmacológico , Hepatite C/tratamento farmacológico , HumanosRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin. Several mutations have been reported to confer resistance to interferon-based treatments. Therefore, there is a need to determine HCV genotypes in Botswana, as these data will guide new treatment guidelines and understanding of HCV epidemiology in Botswana. METHODS: This was a retrospective cross-sectional pilot study utilizing plasma obtained from 55 participants from Princess Marina Hospital in Gaborone, Botswana. The partial core region of HCV was amplified, and genotypes were determined using phylogenetic analysis. RESULTS: Four genotype 5a and two genotype 4v sequences were identified. Two significant mutations - K10Q and R70Q - were observed in genotype 5a sequences and have been associated with increased risk of hepatocellular carcinoma (HCC), while R70Q confers resistance to interferon-based treatments. CONCLUSION: Genotypes 5a and 4v are circulating in Botswana. The presence of mutations in genotype 5 suggests that some patients may not respond to IFN-based regimens. The information obtained in this study, in addition to the World health organization (WHO) recommendations, can be utilized by policy makers to implement DAAs as the new SOC for HCV treatment in Botswana.
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Hepacivirus/genética , Hepatite C/virologia , Mutação , Filogenia , Adulto , Antivirais/uso terapêutico , Botsuana , Carcinoma Hepatocelular/virologia , Estudos Transversais , Farmacorresistência Viral , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Ribavirina/uso terapêuticoRESUMO
Human pegivirus (HPgV) is a positive single-stranded RNA virus in the Flaviviridae family. Phylogenetic analysis reveals the presence of multiple HPgV genotypes with distinct geographic locations. HPgV is of interest because of its potential beneficial impact on HIV disease progression. Despite this, the effects of HPgV in the context of other viral infections, such as hepatitis B virus (HBV), are poorly understood, and data from resource-limited settings are scarce. Therefore, we conducted a cross-sectional analysis of HPgV in HIV/HBV co-infected patients in Ghana. Sera from 100 HIV/HBV co-infected individuals were evaluated for HPgV RNA, and the genotype determined by sequencing the 5' untranslated region. HPgV RNA was detected in 27 samples (27%). Of these, 26 were genotyped successfully with 23 belonging to HPgV genotype 1 and 3 belonging to HPgV genotype 2. The presence of HPgV RNA had no statistically significant impact on CD4 cell count or HBV DNA titers in the HIV/HBV co-infected patients. However, there was a trend towards decreased HBV DNA levels in HPgV RNA-positive patients with CD4 cell count < 200 (p = 0.0626). HPgV co-infection is common in Ghana. The effect of HPgV on HIV or HBV disease among HIV/HBV co-infected patients was minimal. However, decreased HBV DNA levels in HPgV RNA-positive patients with low CD4 cell counts highlight the need for prospective studies of HPgV in HIV and hepatitis co-infected patients, especially in those with advanced HIV disease, to study further the effects of HPgV on liver disease.
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Coinfecção/epidemiologia , Infecções por Flaviviridae/complicações , Vírus GB C , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite Viral Humana/complicações , Adulto , Coinfecção/virologia , Feminino , Infecções por Flaviviridae/epidemiologia , Gana/epidemiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatitis B virus (HBV) infection is a major public health problem worldwide and the major cause of hepatocellular carcinoma (HCC) in South Africa. The role of HBV in HCC is not well understood, although the HBV X gene has been implicated as a critical factor. Data on the HBV X gene in HIV-positive South Africans are limited; thus, we investigated X gene variability in 24 HIV-infected treatment-naïve patients at Dr George Mukhari Academic Hospital. Quantitative and qualitative HBV DNA tests were conducted using real-time and in-house polymerase chain reaction (PCR) assays, respectively, targeting the complete HBV X gene. In-house PCR-positive samples were cloned using the P-Gem T-easy vector System II and sequenced. By phylogenetic analysis, X gene sequences were classified as subgenotype A1 (n = 15), A2 (n = 4), and D1 (n = 4), and one dual infection with subgenotypes as A1 and C. The basal core promoter mutations T1753C, A1762T, and G1764A were identified in the majority of sequences. Genotype D sequences had a 6-nucleotide insertion. In conclusion, subgenotype A1 was predominant, and a rare dual infection of HBV genotype A and C was detected. The 6-nucleotide insertion could represent a unique variant in the region and highlights the need for functional studies of HBV X gene variants, particularly from resource-limited settings.
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Variação Genética , Infecções por HIV/complicações , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Transativadores/genética , Análise por Conglomerados , Genótipo , Vírus da Hepatite B/isolamento & purificação , Hospitais , Humanos , Mutação , Filogenia , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Homologia de Sequência , África do Sul , Proteínas Virais Reguladoras e AcessóriasRESUMO
The human pegivirus (HPgV)-formerly GB virus C-has a beneficial impact on HIV disease progression that has been described in multiple studies. Given the high prevalence of HIV in sub-Saharan Africa and the continuing need to suppress HIV replication, this review provides a comprehensive overview of the existing data on HPgV infection in sub-Saharan Africa, with a particular focus on studies of prevalence and the circulating HPgV genotypes. This review also highlights the need for additional studies of HPgV conducted on the African continent and proposes a research agenda for evaluation of HPgV.