Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.

Fluctuations in serological hepatitis C virus levels in HIV patients.

INTRODUCTION: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have identical transmission routes, explaining the high prevalence of coinfections. The main aim of this study was to detect fluctuations in serological HCV levels in HIV patients. METHODS: We analyzed samples of 147 patients who attended an outpatient service that supports HIV/AIDS patients in São Paulo city. We also recruited 22 HCV-monoinfected patients who attended the Instituto Adolfo Lutz Laboratory in São Paulo city, to compare the test results. Serological testing of the blood samples was performed for the detection of HCV antibodies. The samples were then analyzed using real-time PCR for RNA viral quantification and sequencing. RESULTS: We found that 13.6% of the study population was coinfected with HIV and HCV. In 20% of coinfected patients, fluctuations in serology results were detected in samples collected during the follow-up. No changes in anti-HCV serological markers were observed in HCV-monoinfected patients. An HCV viral load was detected in 9,5% of the samples collected from HIV patients. CONCLUSIONS: Our findings provide important clinical data to public health professionals and highlight the importance of periodic monitoring of HCV/HIV coinfected patients.

Fluctuations in serological hepatitis C virus levels in HIV patients

Abstract INTRODUCTION: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have identical transmission routes, explaining the high prevalence of coinfections. The main aim of this study was to detect fluctuations in serological HCV levels in HIV patients. METHODS: We analyzed samples of 147 patients who attended an outpatient service that supports HIV/AIDS patients in São Paulo city. We also recruited 22 HCV-monoinfected patients who attended the Instituto Adolfo Lutz Laboratory in São Paulo city, to compare the test results. Serological testing of the blood samples was performed for the detection of HCV antibodies. The samples were then analyzed using real-time PCR for RNA viral quantification and sequencing. RESULTS We found that 13.6% of the study population was coinfected with HIV and HCV. In 20% of coinfected patients, fluctuations in serology results were detected in samples collected during the follow-up. No changes in anti-HCV serological markers were observed in HCV-monoinfected patients. An HCV viral load was detected in 9,5% of the samples collected from HIV patients. CONCLUSIONS: Our findings provide important clinical data to public health professionals and highlight the importance of periodic monitoring of HCV/HIV coinfected patients.

Prevalence of naturally occurring amino acid substitutions associated with resistance to hepatitis C virus NS3/NS4A protease inhibitors in São Paulo state.

Hepatitis C (HCV)-infected patients are treated with direct-acting antiviral agents (DAAs) in highly effective, well-tolerated, all-oral regimens. However, naturally occurring resistance-associated amino acid substitutions (RASs) may be selected during treatment. This study aimed to screen naturally occurring RASs NS3/NS4A inhibitors (PIs). Samples were obtained from DAA naïve patients, living in São Paulo state, Brazil. Screening for RASs in the HCV NS3 region was conducted in 859 samples from HCV-infected patients, of which 425 and 434 samples were subtype 1a and 1b, respectively. HCV-RNA was extracted, amplified, and sequenced. The overall prevalence of RASs to HCV PIs was 9.4%. The following RASs were observed in HCV-1a subtype infected patients: V36L (2.6%), T54S (1.6%), V55I/A (1.2% / 8.9%, respectively), Q80K (2.1%), R155K (0.5%), and D168E (0.2%); and in HCV-1b infected patients: V36L (0.7%), T54A/S (0.2% and 0.5%, respectively), V55A (0.5%), Q80K (0.2%), D168E (1.6%), and M175L (0.5%). HCV 1a infected subjects had higher serum viral load than that seen in patients infected with HCV 1b. There was no difference between the proportions of NS3 RASs with regards to geographic distribution within the investigated areas. These findings should be supported by additional studies in Brazil to help in the formation of local clinical guidelines for managing hepatitis C.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study.

OBJECTIVE:: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS:: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS:: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION:: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

High incidence of tuberculosis in patients treated for hepatitis C chronic infection.

Brazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis C carriers and some epidemiological risk scenarios are coincident for both diseases. We analyzed tuberculosis cases that occurred during α-interferon-based therapy for hepatitis C in reference centers in Brazil between 2001 and 2012 and reviewed their medical records. Eighteen tuberculosis cases were observed in patients submitted to hepatitis C α-interferon-based therapy. All patients were human immunodeficiency virus-negative. Nine patients (50%) had extra-pulmonary tuberculosis; 15 (83%) showed significant liver fibrosis. Hepatitis C treatment was discontinued in 12 patients (67%) due to tuberculosis reactivation and six (33%) had sustained virological response. The majority of patients had a favorable outcome but one died. Considering the evidences of α-IFN interference over the containment of Mycobacterium tuberculosis, the immune impairment of cirrhotic patients, the increase of tuberculosis case reports during hepatitis C treatment with atypical and severe presentations and the negative impact on sustained virological response, we think these are strong arguments for latent tuberculosis infection screening before starting α-interferon-based therapy for any indication and even to consider IFN-free regimens against hepatitis C when a patient tests positive for latent tuberculosis infection.

High prevalence of hepatitis B virus subgenotypes A1 and D4 in Maranhão state, Northeast Brazil.

In this study, we determined the prevalence of HBV subgenotypes in Maranhão state, located in northeastern Brazil, where the population is heterogeneous, with a high proportion of African descendants. HBV was detected in 119 of 133 (89.5%) chronic hepatitis B patients, including 103 (86.5%) who were HBeAg-negative. Using phylogenetic analysis of the S/Polymerase region of HBV DNA, subgenotype A1 was found to be the most prevalent (67%), followed by genotype D (28%; subgenotype D4 was detected in 24%, D3 in 3%, and D2 in 1%). Genotype F, clustering with subgenotype F2a, was found in six (5%) patients. The topology of the phylogenetic tree showed that HBV/A1 sequences did not cluster together, suggesting that more than one strain was introduced into Maranhão. On the other hand, HBV/D4 sequences formed a monophyletic cluster, suggesting a single entry of this strain in this population. This study showed that HBV/A1 was the only subgenotype of HBV/A present in the population from Maranhão and indicated that in this region HBV/A1 was not restricted to an Afro-descendant community where it was previously reported, but is widely distributed among general population of HBV chronic carriers. Unexpectedly, we found a high frequency of HBV subgenotype D4. Together with previously reported data on the distribution of HBV/D4 in the world, these findings suggest that this subgenotype was more prevalent in the African continent in the past and may have been introduced in Maranhão by means of the slave trade during the late XVIII century, when the largest number of African slaves arrived to this region.

Pegylated interferon/ribavirin-associated sudden hearing loss in a patient with chronic hepatitis C in Brazil.

Sudden hearing loss is defined as a sensorineural hearing loss, equal to or greater than 30 dB, at three or more consecutive frequencies, which takes place within 72 hours. Both peginterferon and ribavirin are well-known to be associated with significant adverse effects, but sudden hearing loss is uncommon. We report a 65-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon-alpha and ribavirin for chronic hepatitis C. Peginterferon and ribavirin may cause sudden hearing loss that may not recover after discontinuation of therapy. Immediate treatment for all possible etiologies is essential, along with targeted investigations and early referral for an ear, nose and throat specialist. Physicians should be aware of the possible ototoxic effects of peginterferon and ribavirin combination therapy requiring appropriate surveillance.

Pegylated interferon/ribavirin-associated sudden hearing loss in a patient with chronic hepatitis C in Brazil

Sudden hearing loss is defined as a sensorineural hearing loss, equal to or greater than 30 dB, at three or more consecutive frequencies, which takes place within 72 hours. Both peginterferon and ribavirin are well-known to be associated with significant adverse effects, but sudden hearing loss is uncommon. We report a 65-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon-alpha and ribavirin for chronic hepatitis C. Peginterferon and ribavirin may cause sudden hearing loss that may not recover after discontinuation of therapy. Immediate treatment for all possible etiologies is essential, along with targeted investigations and early referral for an Ear, Nose and Throat specialist. Physicians should be aware of the possible ototoxic effects of peginterferon and ribavirin combination therapy requiring appropriate surveillance.

Hepatitis B genotype G and high frequency of lamivudine-resistance mutations among human immunodeficiency virus/hepatitis B virus co-infected patients in Brazil.

In this study, we evaluated the hepatitis B virus (HBV) genotype distribution and HBV genomic mutations among a group of human immunodeficiency virus-HBV co-infected patients from an AIDS outpatient clinic in São Paulo. HBV serological markers were detected by commercially available enzyme immunoassay kits. HBV DNA was detected using in-house nested polymerase chain reaction and quantified by Cobas Amplicor. HBV genotypes and mutations in the basal core promoter (BCP)/pre-core/core regions and surface/polymerase genes were determined by sequencing. Among the 59 patients included in this study, 55 reported prior use of lamivudine (LAM) or tenofovir. HBV DNA was detected in 16/22 patients, with a genotype distribution of A (n = 12,75%), G (n = 2,13%), D (n = 1,6%) and F (n = 1,6%). The sequence data of the two patients infected with genotype G strongly suggested co-infection with genotype A. In 10 patients with viremia, LAM-resistance mutations in the polymerase gene (rtL180M + rtM204V and rtV173L + rtL180M + rtM204V) were found, accompanied by changes in the envelope gene (sI195M, sW196L and sI195M/sE164D). Mutations in the BCP and pre-core regions were identified in four patients. In conclusion, genotype G, which is rarely seen in Brazil, was observed in the group of patients included in our study. A high prevalence of mutations associated with LAM-resistance and mutations associated with anti-HBs resistance were also found among these patients.

Hepatitis B genotype G and high frequency of lamivudine-resistance mutations among human immunodeficiencyvirus/hepatitis B virus co-infected patients in Brazil

In this study, we evaluated the hepatitis B virus (HBV) genotype distribution and HBV genomic mutations among a group of human immunodeficiency virus-HBV co-infected patients from an AIDS outpatient clinic in São Paulo. HBV serological markers were detected by commercially available enzyme immunoassay kits. HBV DNA was detected using in-house nested polymerase chain reaction and quantified by Cobas Amplicor. HBV genotypes and mutations in the basal core promoter (BCP)/pre-core/core regions and surface/polymerase genes were determined by sequencing. Among the 59 patients included in this study, 55 reported prior use of lamivudine (LAM) or tenofovir. HBV DNA was detected in 16/22 patients, with a genotype distribution of A (n = 12,75 percent), G (n = 2,13 percent), D (n = 1,6 percent) and F (n = 1,6 percent). The sequence data of the two patients infected with genotype G strongly suggested co-infection with genotype A. In 10 patients with viremia, LAM-resistance mutations in the polymerase gene (rtL180M + rtM204V and rtV173L + rtL180M + rtM204V) were found, accompanied by changes in the envelope gene (sI195M, sW196L and sI195M/sE164D). Mutations in the BCP and pre-core regions were identified in four patients. In conclusion, genotype G, which is rarely seen in Brazil, was observed in the group of patients included in our study. A high prevalence of mutations associated with LAM-resistance and mutations associated with anti-HBs resistance were also found among these patients.

Risk factors associated with hepatitis C among patients co-infected with human immunodeficiency virus: a case-control study.

A case-control study was carried out to assess the risk factors associated with hepatitis C in patients infected with human immunodeficiency virus. One hundred eighteen patients tested positive for hepatitis C virus (HCV) and were included as cases, and 117 tested negative for HCV and were included as controls. Information was collected through a questionnaire. The risk factors that showed a significant association with co-infection by multivariate analysis were an age of 30-39 years (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.31-16.43), an age of 40-49 years (OR = 6.48, 95% CI = 1.70-24.78), an age > 50 years (OR = 7.50, 95% CI = 1.54-36.68), use of intravenous drugs (OR = 25.46, 95% CI = 4.91-131.88), use of inhaled illicit drugs (OR = 3.56, 95% CI = 1.22-10.44), anal intercourse (OR = 3.93, 95% CI = 1.27-12.13), a sexual partner with a history of liver disease (OR = 5.45, 95% CI = 1.33-22.32), a sexual partner with a history of blood transfusions (OR = 4.79, 95% CI = 0.95-24.19), and sexual partner with a history of intravenous drug use (OR = 3.46, 95% CI = 1.24-9.65).

Hepatitis C in patients co-infected with human immunodeficiency virus. A review and experience of a Brazilian ambulatory.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same transmission mechanisms. The prevalence of HCV in the HIV-infected population varies from region to region, throughout the world, depending on different exposure factors to both viruses. Co-infection with HIV accelerates the progression of the disease caused by HCV, appears to worsen the progression of the HIV infection and increases HCV transmission. Therefore, clinical management and treatment of HCV is a priority in medical facilities that receive HIV-infected patients. Clinical management of these patients involves specific diagnostic procedures and appropriately trained medical staff. The indication of treatment should meet specific clinical and laboratory criteria. There are a number of drugs currently available to treat hepatitis C in co-infected patients.

Hepatitis C in patients co-infected with human immunodeficiency virus. A review and experience of a Brazilian ambulatory

O virus da hepatite C e o HIV compartilham os mesmos mecanismos de transmissão. A prevalência da infecção pelo vírus da hepatite C em pacientes co-infectados pelo HIV varia em diferentes regiões do mundo, a depender dos diferentes fatores de exposição para ambos os vírus. A co-infecção com o HIV acelera a progressão da doença causada pelo vírus da hepatite C, agrava a progressão da infecção causada pelo HIV e aumenta o risco de transmissão do vírus da hepatite C. Portanto, a atenção clínica e o tratamento da infecção pelo vírus da hepatite C deveriam ser prioridade nas unidades de atendimento a pacientes infectados pelo HIV. O manejo clínico desses pacientes envolve procedimentos diagnósticos específicos e equipe médica treinada para esse fim. O tratamento dessa condição deve seguir critérios clínicos e laboratoriais específicos. Atualmente já são disponíveis medicamentos para o tratamento da hepatite C em pacientes co-infectados pelo HIV.

Clinical laboratory assessment of hepatitis C and HIV coinfected patients according to the antiretroviral therapy received.

During the year of 2001, a retrospective, descriptive study in order to determine the influence of the antiretroviral therapy received by 111 HIV-HCV coinfected patients who had undergone at least one liver biopsy was conducted, 74 of them were treated with a protease inhibitor regimen (WPI), and 37 with a non-protease inhibitor regimen (NPI). The main characteristics found were: a young patient population (mean age 41 years old in both groups), composed in most part of male individuals (74.3% WPI and 51.4% NPI) with previous risk factors for both infections (WPI 93.2% and NPI 89.2%). The most significant findings included AIDS-defining disease (WPI 18.9% and NPI 13.5% of the cases), elevated hepatic enzyme levels (WPI: SGOT 52.1 and NPI 53.2), absence of liver disease-related symptoms (16.2% for both groups), average CD4 count > 350 for both groups (WPI 362.2 and NPI 378.1), predominantly low-grade fibrosis in both populations (0-2 in 63.6% of WPI patients and in 80% of NPI patients), with necro-inflammatory activity ranging from 5-7 in 51.3% and 42.9% of WPI patients and NPI patients, respectively. It is suggested a sequential biopsy to better evaluate the evolution of the hepatic disease, according to the HAART regimen received.

Clinical laboratory assessment of hepatitis C and HIV coinfected patients according to the antiretroviral therapy received

Durante o ano de 2001, um estudo retrospectivo e descritivo foi efetuado a fim de determinar a influência da terapia antirretroviral recebida por 111 pacientes co-infectados HIV-HCV que tinham se submetido ao menos a uma biopsia hepática. Destes, 74 foram tratados com um regime contendo inibidor da protease (WPI) e 37 com um regime do não contendo inibidor da protease (NPI). As características principais encontradas eram: uma população de pacientes jovem (idade média 41 anos em ambos os grupos), composta na maior parte por indivíduos masculinos (74,3% WPI e 51,4% NPI) com fatores de risco precedentes para ambas as infecções (WPI 93,2% e NPI 89,2%). Os achados mais significativos incluíram doença definidora de AIDS (WPI 18,9% e NPI 13,5% dos casos), nível elevado de enzimas hepáticas (WPI: SGOT 52.1 e NPI 53.2), ausência de sintomas relacionáveis à doença hepática (16.2% para ambos os grupos), CD4 contagem média 350 para ambos os grupos (WPI 362.2 e NPI 378.1), fibrose predominantemente de baixo grau em ambas as populações (0-2 em 63,6% de pacientes de WPI e em 80% de pacientes de NPI), com atividade necro-inflamatória que varia de 5-7 em 51.3% e em 42,9% de pacientes de WPI e de pacientes de NPI, respectivamente. Foi concluído que uma nova biópsia hepática deveria ser executada em todos os pacientes para determinar melhor qual a diferença no avanço da doença em ambos os grupos.