Characterization of clinical predictors of naturally occurring NS3/NS4A protease polymorphism in genotype 1 hepatitis C virus mono and HIV co-infected patients.

Spontaneously occurring resistance may impair the success of protease inhibitors based regimens in HCV treatment. This study aimed to evaluate associations between amino acid substitutions in NS3/NS4A domain and clinical features of 247 HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at least one resistance-associated substitution (RAS). The following RASs were detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A amino acid substitutions.

Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil.

BACKGROUND: HBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort. METHODS: A retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression. RESULTS: A total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48.9%) patients were HBeAg positive and 44 (51.1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (p = 0.047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0.001) and ALT levels above normality (p = 0.038). CONCLUSION: Prolonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.

Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype-1 patients with or without HIV coinfection.

BACKGROUND: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. METHODS: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. RESULTS: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. CONCLUSIONS: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample.

[Interviews with family members: a fundamental tool for planning the disclosure of a diagnosis of HIV/aids for children and adolescents]. / Entrevista com os familiares: um instrumento fundamental no planejamento da revelação diagnóstica do HIV/Aids para crianças e adolescentes.

The scope of this study was to present the participation of caregivers in creating strategies for disclosure of their condition to HIV-positive children, as well as discussing the interventions that might contribute to overcoming the difficulties that commonly prevent family members from accepting this process. The participants included 23 caregivers of 18 patients referred for diagnosis disclosure, monitored at two pediatric AIDS units in the municipality of São Paulo, Brazil. This is a qualitative study and data were collected through semi-structured interviews. The results showed that legitimating reasons why caregivers are reluctant to disclose the diagnosis to the children, as well as their motivations, are interventions that contribute to reduce resistance, facilitating the acceptance of disclosure. The collaboration of caregivers has provided valuable insights for conducting the work, and has enabled the establishment of a receptive and supportive relationship minimizing inhibitions that could be harmful to the continuity of the process.

Hepatitis delta in HIV/HBV co-infected patients in Brazil: is it important?

OBJECTIVES: This study was carried out to evaluate the prevalence of hepatitis delta virus (HDV) among human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infected patients from São Paulo, in the Southeast Region of Brazil. METHODS: A total of 3259 HIV patients with serological markers for HBV were initially enrolled in the study. Among these patients, 154 (4.7%) were hepatitis B surface antigen (HBsAg)-reactive. Serum samples were obtained from 86 HBsAg-positive patients and were submitted to anti-HDV serological assay. RESULTS: One (1.2%) HIV/HBV patient was found to be anti-HDV-positive, and the HDV infection was confirmed by PCR. Phylogenetic analysis showed that this HDV sequence grouped with other HDV genotype 1 sequences from Mediterranean European countries, suggesting that this virus has a common ancestor with HDV from that region. This patient was probably infected by sexual transmission, as he reported unprotected sexual intercourse with multiple partners over the course of many years but denied intravenous drug use or any travel to the Brazilian Amazon, an area known to have a high HDV prevalence. CONCLUSIONS: HDV infection is infrequent in the Southeast Region of Brazil, however there have been a few cases in this region. HIV/HBV patients are at potential risk for HDV infection, therefore investigations for the presence of HDV infection must be carried out in these patients.

Entrevista com os familiares: um instrumento fundamental no planejamento da revelação diagnóstica do HIV/Aids para crianças e adolescentes / Interviews with family members: a fundamental tool for planning the disclosure of a diagnosis of HIV/aids for children and adolescents

O estudo teve como objetivo apresentar a participação dos cuidadores na construção de estratégias para a comunicação do HIV às crianças soropositivas, assim como, discutir as intervenções que contribuiriam para a superação das dificuldades que comumente impedem os familiares a aceitarem esse processo. Participaram 23 cuidadores de 18 pacientes com indicação para revelação diagnóstica, acompanhados em dois serviços de Aids pediátrica no município de São Paulo, Brasil. Trata-se de pesquisa qualitativa e os dados foram coletados através de entrevistas semidirigidas. Os resultados demonstraram que legitimar os motivos pelos quais os cuidadores relutam em divulgar o diagnóstico às suas crianças, assim como suas motivações, são intervenções que contribuem para diluir resistências, facilitando a aceitação da revelação. A colaboração dos responsáveis forneceu subsídios valiosos para o direcionamento do processo de revelação diagnóstica, além de ter possibilitado o estabelecimento de um vínculo receptivo e favorável, capaz de minimizar inibições que poderiam ser prejudiciais à continuidade do processo.

The scope of this study was to present the participation of caregivers in creating strategies for disclosure of their condition to HIV-positive children, as well as discussing the interventions that might contribute to overcoming the difficulties that commonly prevent family members from accepting this process. The participants included 23 caregivers of 18 patients referred for diagnosis disclosure, monitored at two pediatric AIDS units in the municipality of São Paulo, Brazil. This is a qualitative study and data were collected through semi-structured interviews. The results showed that legitimating reasons why caregivers are reluctant to disclose the diagnosis to the children, as well as their motivations, are interventions that contribute to reduce resistance, facilitating the acceptance of disclosure. The collaboration of caregivers has provided valuable insights for conducting the work, and has enabled the establishment of a receptive and supportive relationship minimizing inhibitions that could be harmful to the continuity of the process.