ABSTRACT Among individuals coinfected with HCV and HIV, studies of mortality from non-hepatic causes have shown inconsistent results. The aim of this study was to investigate the contribution of HCV and HIV co-infection to mortality from hepatic and non-hepatic causes in Brazil. This retrospective cohort study included blood donors from Fundação Pró-Sangue de São Paulo (FPS) who were followed from 1994 to 2016 to compare mortality and its causes between HIV-HCV coinfected individuals versus those seronegative for all tested infections. Records from the FPS database and the Mortality Information System were linked through a probabilistic record Relationship (RL). The Hazard Ratio (HR) was estimated using Cox multiple regression models. HCV-HIV coinfected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 14.54), non-liver neoplasms (HR = 2.55), infections (HR = 10.37) and liver disease (HR = 7.0). In addition, HCV mono-infected individuals compared to seronegative individuals had a higher risk of death from all causes (HR = 2.23), liver cancer (HR = 32.21), liver disease (HR = 14.92), infection (HR = 3.22), and trauma (HR = 1.68). Individuals coinfected with HCV and HIV have increased overall mortality and death due to infections, liver diseases and non-liver neoplasms as compared to those uninfected with HCV and HIV.

ABSTRACT Introduction Hepatitis C virus (HCV) can be vertically transmitted from mother to fetus. We evaluated knowledge about HCV vertical transmission in female blood donors who became pregnant following detection of HCV in their donated blood. Methods This was a retrospective descriptive study of females seen at a single blood bank in Sao Paulo, Brazil who were diagnosed with HCV infection in their donated blood. HCV-infected donors who subsequently became pregnant were invited to participate through letters or phone calls. Individuals who agreed to participate were interviewed by questionnaire to evaluate their knowledge on HCV vertical transmission. Results Among 282 HCV-positive female blood donors, 69 reported becoming pregnant after their HCV diagnosis in donated blood. While 24 of these women were successful treated for their infection prior to becoming pregnant, 45 (65.2%) were at risk for vertical HCV transmission either because they had never been treated for HCV, were pregnant before treatment or became pregnant after unsuccessful treatment. Of the 59 women who responded to the question of whether they were informed about the risk of HCV vertical transmission, 58 (98.3%) reported never receiving this information either after obtaining their blood donation results or during their pregnancy. Conclusion The lack of knowledge of HCV-infected women on the possibility for mother-to-child transmission of this virus highlights the critical need to improve communication about pregnancy-related risks between health professionals and HCV-infected women of childbearing age.

ABSTRACT The Hepatitis C virus (HCV) infection is a public health problem. The high level of HCV replication and its lack of post-transcriptional correction mechanisms results in the emergence of viral variants and the difficulty in determining polymorphisms and variants that contain the substitutions associated with resistance towards new antivirals. The main focus of this study was to map the NS5A and NS5B polymorphisms and resistance mutations to new antiviral drugs in HCV strains genotype 1 from patients with chronic hepatitis C infection. Serum samples were collected from patients who underwent routine viral load tests at the Instituto Adolfo Lutz, Sao Paulo city, Brazil. A total of 698 and 853 samples were used for the characterization of NS5A and NS5B regions, respectively, which comprise the HCV genotypes 1a and 1b. The prevalence of resistance mutations found in the NS5A region was 6.4%, with Y93H, L31M, Q30R, and Y93N as the main resistance-associated substitutions (RAS). No NS5B-associated RAS was observed for any of the analyzed drugs. These findings support that the RAS test should be offered to individuals with poor response to double combination regimens prior to treatment initiation, thereby assisting strain vigilance and selection of effective treatment or retreatment options using DAA regimens.

ABSTRACT Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10; p<0.001) and occurrence of liver cirrhosis (PR 2.06; 95% CI 1.11-3.83; p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.

OBJECTIVE: To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.

Objectives:A cross-sectional study on prevalence of HBV and HDV infection, risk factors and genotype distribution of HBV infection was conducted among 848 HIV-infected patients in Mato Grosso do Sul, Central Brazil.Methods:Serum samples of 848 participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis surface antibody (anti-HBs). HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV, and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction. Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi-square test and Fisher's exact test were used to compare variables and to evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg positivity) and risk factors.Results:Among the 848 HIV infected patients investigated 222 had serological markers of HBV infection. The prevalence rate of HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4–3.5%); 484 (57.1%) patients were susceptible for HBV infection. There were no cases of anti-HDV positive and only one (0.1%) anti-HCV-positive case among the HIV-HBV coinfected patients. Male gender, increasing age, family history of hepatitis, use of illicit drug, and homosexual activity were independent factors associated with HBV exposure. The phylogenetic analysis based on the S gene region revealed the presence of genotypes D (76.9%), F (15.4%) and A (7.7%) in the study sample.Conclusion:This study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals.

The objective of this study was to assess the prevalence of barriers to interferon treatment in a population of HIV/HCV coinfected patients. A cross-sectional study was conducted at two AIDS Outpatient Clinics in Brazil. The study included all HIV infected patients followed at these institutions from January 2005 to November 2007. Medical records of 2,024 HIV-infected patients were evaluated. The prevalence of anti-HCV positive patients among them was 16.7%. Medical records of HCV/HIV coinfected patients were analyzed. 189 patients with the following characteristics were included in our study: mean age 43 years; male gender 65%; former IDUs (52%); HCV genotype 1 (66.4%); HCV genotype 3 (30.5%); median CD4+ T cell count was 340 cells/mm³. Among 189 patients included in the analyses, only 75 (39.6%) were considered eligible for HCV treatment. The most frequent reasons for non-treatment were: non-compliance during clinical follow-up (31.4%), advanced HIV disease (21.9%), excessive alcohol consumption or active drug use (18.7%), and psychiatric disorders (10.1%). CONCLUSIONS: In Brazil, as in elsewhere, more than half of HIV/HCV coinfected patients (60.4%) have been considered not candidates to received anti-HCV treatment. The main reasons may be deemed questionable: non-adherence, drug abuse, and psychiatric disease. Our results highlight the importance of multidisciplinary teams to optimize the access of coinfected patients to HCV treatment.

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.

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.

O objetivo do presente estudo foi avaliar a prevalência e os fatores de risco associados à infecção pelo vírus da hepatite C (VHC) em um grupo de pacientes soropositivos para o HIV. Analisamos os prontuários médicos de 1.457 pacientes. O diagnóstico laboratorial de infecção pelo VHC foi feito utilizando-se ELISA de terceira geração. Uma parte dos pacientes soropositivos para VHC foram também submetidos à realização de PCR. Os pacientes soropositivos para VHC foram analisados em relação aos fatores de risco para ambas as infecções. A prevalência de pacientes soropositivos para VHC foi de 17,7% (258 pacientes). 82 desses pacientes foram testados para VHC por PCR e 81 (98%) apresentaram-se com resultado positivo. 151 (58,5%) referiram uso de drogas endovenosas (UDE), 42 (16,3%) eram parceiros sexuais de pacientes infectados pelo HIV, 23 (8,9%) eram homossexuais masculinos, 12 (4,7%) tinham recebido transfusão sanguínea, 61 (17,5%) referiram promiscuidade sexual, 14 (5,4%) negaram qualquer fator de risco, 12 (4,7%) eram parceiros sexuais de UDE. 204 pacientes referiram apenas um fator de risco, 51 referiram dois diferentes fatores de risco e três referiram três diferentes fatores de risco. Entre os pacientes que referiram apenas um fator de risco, 28 em 204 (10,9%) eram parceiros sexuais de pacientes infectados pelo HIV. Embora o uso de drogas endovenosas tenha sido o fator de risco mais importante na determinação da co-infecção, a transmissão sexual parece ter contribuído para a alta soroprevalência do VHC nesse grupo de pacientes.

The objective of this study was to evaluate the prevalence and risk factors associated with HCV infection in a group of HIV seropositive patients. We analyzed the medical records of 1,457 patients. All patients were tested for HCV infection by third generation ELISA. Whenever possible, a sample of the positive patients was also tested for HCV by PCR. HCV positive patients were analyzed according to their risk factors for both infections. The prevalence of anti-HCV positive patients was 17.7% (258 patients). Eighty-two (82) of these patients were also tested by PCR and 81 were positive for HCV virus (98%). One hundred fifty-one (58.5%) were intravenous drug users (IDU); 42 (16.3%) were sexual partners of HIV patients; 23 (8.9%) were homosexual males; 12 (4.7%) had received blood transfusion; 61 (17.5%) had promiscuous sexual habits; 14 (5.4%) denied any risk factor; 12 (4.7%) were sexual partners of IDU. Two hundred four patients mentioned only one risk factor. Among them, 28 (10.9%) were sexual partners of HIV-positive patients. Although intravenous drug use was the most important risk factor for co-infection, sexual transmission seemed to contribute to the high HCV seroprevalence in this group of patients.

O objetivo do presente trabalho é avaliar a prevalência da infecção causada pelos vírus da hepatite B (HBV) e da hepatite C (HCV) em um grupo de pacientes infectados pelo HIV e acompanhados em uma única instituição desde 1996. 1.693 pacientes infectados pelo HIV (1.162 do sexo masculino e 531 do sexo feminino) foram testados para o HBV. Os marcadores virológicos utilizados para o HBV foram o HBsAg e o anti-HBc total por ELISA. 1.457 pacientes (1009 do sexo masculino e 448 do sexo feminino) foram testados para o HCV. Realizou-se a detecção dos anticorpos para o HCV através da reação de ELISA. Um grupo de pacientes anti-HCV positivos realizou PCR (polimerase chain reaction) para pesquisa do HCV, para confirmação da infecção. Dos 1.693 pacientes testados para HBV, 654 (38,6%) e 96 (5,7%) eram anti-HBc total e HBsAg positivos, respectivamente. Dos 1.457 pacientes testados para HCV, 258 (17,7%) eram anti-HCV positivos. 82 desses pacientes realizaram PCR para HCV e 81 foram positivos (98%). Dos 1.411 pacientes testados para ambos os vírus HBV e HCV 26 (1,8%) foram positivos para ambos os vírus.

The objective of this study was to evaluate the prevalence of hepatitis B and C viruses in a group of HIV infected patients, followed at a single institution since 1996. 1,693 HIV positive patients (1,162 male, 531 female) were tested for HBV infection. Virological markers for HBV included HBsAg and total anti-HBc by ELISA. 1,457 patients (1,009 male, 448 female) were tested for HCV infection. Detection of HCV antibodies was carried out by ELISA. A sample of HCV antibody positive patients was tested for HCV by PCR to confirm infection. Of 1,693 patients tested for HBV, 654 (38.6%) and 96 (5.7%) were anti-HBc and HBsAg positive, respectively. Of 1,457 patients tested for HCV, 258 (17.7%) were anti-HCV positive. 82 of these patients were also tested by PCR and 81 were positive (98%). Of 1,411 patients tested for HBV and HCV 26 (1.8%) were positive for both viruses.