Abstracts

Introduction

HIV infection has a pandemic aspect and is extremely severe, making it one of the most important current health problems ¹1 . Rodrigues-Junior AL, Castilho EA. A epidemia da AIDS no Brasil, 1991-2000: descrição espaço-temporal. Rev Soc Bras Med Trop 2004; 37:312-7. ^{, 2}2 . Ministério da Saúde. Guia de vigilância epidemiológica. Brasília: Ministério da Saúde; 2005. (Série A. Normas e Manuais Técnicos). ^{, 3}3 . Ministério da Saúde. Prevalências e frequências relativas de doenças sexualmente transmissíveis (DST) em populações selecionadas de seis capitais brasileiras, 2005. Brasília: Ministério da Saúde; 2008. (Série G. Estatística e Informação em Saúde).. Hepatitis viruses cause liver infections of different types, depending on the etiologic agent, the most common being the type A (HAV), B (HBV), and C (HCV) viruses ²2 . Ministério da Saúde. Guia de vigilância epidemiológica. Brasília: Ministério da Saúde; 2005. (Série A. Normas e Manuais Técnicos). ^{, 4}4 . Braga WSM, Castilho MC, Santos ICV, Moura MAS, Segurado AC. Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin. Rev Soc Bras Med Trop 2006; 39:519-22. ^{, 5}5 . Fonseca JCF. História natural da hepatite crônica B. Rev Soc Bras Med Trop 2007; 40:672-7.. The importance of viral hepatitis in public health is well known due to the large number of infected individuals and the complications caused by the infection ²2 . Ministério da Saúde. Guia de vigilância epidemiológica. Brasília: Ministério da Saúde; 2005. (Série A. Normas e Manuais Técnicos)..

Hepatitis B and C viruses and the HIV virus share the most important forms of transmission, in particular sexual, by blood, and vertical (mother to child) transmission. Infections by these viruses present a dynamic interaction, amplifying each other and leading to greater morbidity and mortality in coinfected patients. HIV-infected individuals who also develop acute hepatitis B are 5 to 6 times more likely to become chronic carriers of HBV and are also at greater risk of developing severe liver diseases that may result in death ⁶6 . Lopes EPA, Silva AE, Sette Junior H, Guimarães RX, Ferraz ML. Autoantibodies before, during and after administration of recombinant interferon-a for chronic viral hepatitis. Rev Inst Med Trop São Paulo 1995; 37:455-60. ^{, 7}7 . Corrêa MCJM, Barone AA, Cavalheiro NP, Tengan FM, Guastini C. Prevalence of hepatitis B and C in the sera of patients with HIV infection in São Paulo, Brasil. Rev Inst Med Trop São Paulo 2000; 42:81-5..

The HIV virus accelerates the evolution of liver diseases caused by hepatitis B and C, especially in patients with greater immune deficiencies. Thus, coinfected patients suffer more severe consequences than mono-infected patients. For example, HIV/HCV coinfected individuals show a faster progression of fibrosis, the risk of vertical transmission increases from 6% to 20%, and the risk of sexual transmission increases by 3%. Among HIV/HBV coinfected individuals, the infection is more severe and causes more aggressive cases of cirrhosis and liver cancer. In this situation, the risk of cirrhosis increases 4.2-fold, mortality also increases, and, in some cases, the hepatitis B virus can be reactivated ⁸8 . Amaral ISA, Almeida ML, Alves FT, Móia LJMP, Conde SRSS. Epidemiologia de pacientes coinfectados HIV/HCV atendidos na Fundação Santa Casa de Misericórdia do Pará. Rev Para Med 2007; 21:15-24. ^{, 9}9 . Soriano V, Puoti M, Bonacini M. Care of patients with chronic hepatitis B and HIV coinfection: recommendations from an HIV-HBV international panel. AIDS 2005; 19:221-40. ^{, 10}10 . Patel P, Davis S, Tolle M, Mabikwa V, Anabwani G. Prevalence of hepatites B and hepatitis C coinfections in an adult HIV centre population in Gaborone, Botswana. Am J Trop Med Hyg 2011; 85:390-4..

According to Soriano et al. ⁹9 . Soriano V, Puoti M, Bonacini M. Care of patients with chronic hepatitis B and HIV coinfection: recommendations from an HIV-HBV international panel. AIDS 2005; 19:221-40., the prevalence of patients coinfected with HIV/AIDS and hepatitis B and C varies worldwide because of the different forms of transmission. Clinical studies conducted in Brazil show that, among HIV/AIDS-infected individuals, about 6% were positive for HBsAg, while anti-HCV positivity varies from 5 to 18% ⁹9 . Soriano V, Puoti M, Bonacini M. Care of patients with chronic hepatitis B and HIV coinfection: recommendations from an HIV-HBV international panel. AIDS 2005; 19:221-40. ^{, 10}10 . Patel P, Davis S, Tolle M, Mabikwa V, Anabwani G. Prevalence of hepatites B and hepatitis C coinfections in an adult HIV centre population in Gaborone, Botswana. Am J Trop Med Hyg 2011; 85:390-4..

The main purpose of this study is to estimate the prevalence of HIV/HBV and HIV/HCV coinfections among notifiable AIDS cases in Brazil, as well as to describe the epidemiological profile of these cases.

Material and methods

This study examined the data of all HIV-positive patients who were reported as AIDS patients in Brazil and who met the criteria that define an AIDS case. Data was obtained from various sources, including the Notifiable Diseases Information System (SINAN), the Laboratory Tests Control System (SISCEL), and Medication Logistics Control System (SICLOM), which are databases of the Brazilian Ministry of Health.

AIDS cases in children and adults from 1999 to 2010 were obtained from the SINAN database. From the SISCEL and SICLOM databases, the patients’ records during the period of 2000 to 2010 that met the following criteria were selected: (i) TCD4+ cell count less than expected for the age and detectable viral load; (ii) TCD4+ cell count less than expected for the age and use of medication registered in SICLOM; (iii) TCD4+ cell count less than expected for the age, detectable viral load, and use of medication ¹¹11 . Programa Nacional de DST e AIDS, Secretaria de Vigilância em Saúde, Ministério da Saúde. Critérios de definição de casos de AIDS em adultos e crianças. Brasília: Ministério da Saúde; 2005..

Cases of viral hepatitis B and C were obtained from SINAN’s notifications for the period 1999 to 2010. For hepatitis B, cases that presented at least one of the following serum markers were considered: HBsAg, Anti-HBc IgM, or HBeAg; and for hepatitis C, those with the following markers were considered: anti-HCV and HCV-RNA ²2 . Ministério da Saúde. Guia de vigilância epidemiológica. Brasília: Ministério da Saúde; 2005. (Série A. Normas e Manuais Técnicos)..

Linkage between AIDS and hepatitis B and C cases were used to estimate the prevalence of HIV/HBV and HIV/HCV coinfection.

The database initially contained 371,631 AIDS cases between 1999 and 2010. 11 records that did not contain information about the city of residence, 901 records that did not contain the birth date, and 47 with inconsistent birth date were excluded, bringing the final total to 370,672 AIDS cases (99.7%).

The variable “category of exposure” (related to AIDS) used in the analysis was extracted from the SINAN database. The categories “heterosexual”, “homosexual”, and “bisexual” were regrouped under the category “sexual transmission”, while the categories “transfusion” and “hemophiliac” were regrouped under “blood transmission”.

A logistic regression model was used to estimate the chance of patients being coinfected depending on certain socio-demographic variables. The measure of association presented is the odds ratio (OR), with corresponding 95% confidence intervals (95%CI). Separate analyses were conducted for HIV/HBV and HIV/HCV coinfections. Analyses were conducted using Stata v.12 software (Stata Corp., College Station, USA).

Results

In Brazil, 370,672 AIDS cases were reported in the period of 1999 to 2010, 86.3% of which were registered in the SINAN database and 13.7% in the SISCEL and SICLOM databases. Globally, 50.7% of these notifications came from the Southeast region, followed by the South (22.9%), Northeast (14.5%), Central (6.2%), and North (5.7%). AIDS patients are, on average, 43 years old (median = 43 years), and 24.2% of them have 4 to 7 years of schooling. Most of these patients are male (61.0%), white (35.9%), and fall into the category of sexual exposure (64.9%).

Record linkages of the AIDS and viral hepatitis B and C databases allowed for detection of 3,724 HIV/HBV-coinfected and 5,932 HIV/HCV-coinfected individuals. Thus, we observed that 1% and 1.6%, respectively, of the notifiable AIDS cases presented HBV/HIV and HCV/HIV coinfections during the period 1999 to 2010.

Table 1 shows that HIV/AIDS-infected individuals (coinfected and non-coinfected) are mostly males. It is also notable that 81.0% and 73.7%, respectively, of HBV and HCV-coinfected individuals are male. Thus, women are less likely to become coinfected than men (HBV/HIV: OR =0.39, 95%CI: 0.35-0.42; HCV/HIV: OR = 0.78, 95%CI: 0.73-0.83). The chance of coinfection increases with age; it is three times higher in older individuals coinfected with HBV than patients aged 24 and younger; among those coinfected with HCV, the chance can be up to 12 times higher.

The geographical distribution of individuals coinfected with hepatitis B shows that the Southeast region has 57.1% of all notifiable cases, followed by the South (23.2%), and the Central (7.7%) regions (Figure 1). Among those coinfected with hepatitis C, the Southeast region has 65.9% of all notifiable cases, also followed by the South (28.5%), as showed in Figure 1. According to distribution by race/color, most patients are white: 43.8% and 48.2%, respectively, of HBV and HCV coinfected individuals. With regard to schooling, most individuals coinfected with HBV have had at least 8 years of formal education (32.9%) and, among those coinfected with HCV, 34.6% have had 4-7 years (Table 1).

The logistic regression model shows that, in relation to schooling, patients with at least 8 years of formal education are 26% more likely to have HIV/HBV coinfection when compared to patients with no schooling. Among the HIV/HCV coinfected patients, the chance of coinfection increases with more years of schooling – up to twice as high (Table 1).

Most cases fell into the category of exposure to AIDS through sexual activity (homosexual, bisexual, and heterosexual), followed by injecting drug users (IDU). The percentage of blood exposure is below 1% for all coinfected individuals (Table 1). However, the chance for coinfections increases 2- to 6-fold for HBV and HCV, respectively, when the IDU category is compared with sexual exposure.

Discussion

For this study, we used positive symptomatic cases of hepatitis B and C recorded in the SINAN database. It has been suggested that the number of viral hepatitis cases in the official databases are underestimated ⁶6 . Lopes EPA, Silva AE, Sette Junior H, Guimarães RX, Ferraz ML. Autoantibodies before, during and after administration of recombinant interferon-a for chronic viral hepatitis. Rev Inst Med Trop São Paulo 1995; 37:455-60. ^{, 7}7 . Corrêa MCJM, Barone AA, Cavalheiro NP, Tengan FM, Guastini C. Prevalence of hepatitis B and C in the sera of patients with HIV infection in São Paulo, Brasil. Rev Inst Med Trop São Paulo 2000; 42:81-5. ^{, 12}12 . Camargo Jr. KR, Coeli CM. Reclink: aplicativo para o relacionamento de bases de dados, implementando o método probabilistic record linkage. Cad Saúde Pública 2000; 16:439-47.. Besides that, we understand that the undernotification of viral hepatitis, which can also be related to limited access to serologic diagnosis of HCV and HBV, may fluctuate between regions of Brazil. Therefore, comparisons of stratified data estimated by region might be problematic and biased.

A potential weakness of using information from official databases is related to its accuracy (misclassification) and potential under-notification, which might introduce outcome misclassification (coinfection identification), making estimates of measures of effect (for instance, odds ratios) prone to bias. However, there is no evidence that the linkage procedure or that the case under-notification processes are not equal according to exposure variables, such as gender, age group, race, education and category of transmission, satisfying the criteria for the interpretation of the results presented in Table 1. Nevertheless, this study permitted an important evaluation of HBV/HIV and HCV/HIV coinfections in Brazil using information obtained via merging secondary databases from the Brazilian Ministry of Health, without the need to conduct seroprevalence research. Furthermore, it allowed for a description of the epidemiologic profile of individuals coinfected with HBV/HIV and HVC/HIV in recent years in Brazil, as well as the identification of potential risk factors associated with these coinfections. In our study, coinfection prevalence is estimated considering all notifiable and available HIV cases from the Brazilian Ministry of Health’s official databases. In order to reduce probability of undernotification, we considered information from different sources (SINAN, SISCEL, SICLOM). It is also important to highlight that notifiable HIV/AIDS cases in Brazil receive medicine for treatment free of charge, which may contribute to improved data quality.

Even though the estimates of coinfections may be underestimated, our study has corroborated many results from the literature ¹1 . Rodrigues-Junior AL, Castilho EA. A epidemia da AIDS no Brasil, 1991-2000: descrição espaço-temporal. Rev Soc Bras Med Trop 2004; 37:312-7. ^{, 3}3 . Ministério da Saúde. Prevalências e frequências relativas de doenças sexualmente transmissíveis (DST) em populações selecionadas de seis capitais brasileiras, 2005. Brasília: Ministério da Saúde; 2008. (Série G. Estatística e Informação em Saúde). ^{, 4}4 . Braga WSM, Castilho MC, Santos ICV, Moura MAS, Segurado AC. Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin. Rev Soc Bras Med Trop 2006; 39:519-22. ^{, 13}13 . Treitinger A, Spada C, Ferreira LA, Neto MS, Reis M, Verdi JC, et al. Hepatitis B and hepatitis C prevalence among blood donors and HIV-1 infected patients in Florianopolis-Brazil. Braz J Infect Dis 2000; 4:192-6.. We observe that the prevalence of HIV/AIDS in the population is greater among men than women with approximately two infected men for every woman. Similar results were found in this study in relation to hepatitis B and C infections, helping to explain why more than 80% of coinfected individuals are male ¹1 . Rodrigues-Junior AL, Castilho EA. A epidemia da AIDS no Brasil, 1991-2000: descrição espaço-temporal. Rev Soc Bras Med Trop 2004; 37:312-7. ^{, 3}3 . Ministério da Saúde. Prevalências e frequências relativas de doenças sexualmente transmissíveis (DST) em populações selecionadas de seis capitais brasileiras, 2005. Brasília: Ministério da Saúde; 2008. (Série G. Estatística e Informação em Saúde). ^{, 4}4 . Braga WSM, Castilho MC, Santos ICV, Moura MAS, Segurado AC. Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin. Rev Soc Bras Med Trop 2006; 39:519-22. ^{, 13}13 . Treitinger A, Spada C, Ferreira LA, Neto MS, Reis M, Verdi JC, et al. Hepatitis B and hepatitis C prevalence among blood donors and HIV-1 infected patients in Florianopolis-Brazil. Braz J Infect Dis 2000; 4:192-6.. The principal source of infection by hepatitis B and HIV is sexual, which is also observed in coinfected patients, especially men who have sex with men, a category that corresponds to 32% of all coinfections among males. The main form of hepatitis C transmission is contact with contaminated blood, and this mechanism is also one of the main forms of HIV transmission ⁴4 . Braga WSM, Castilho MC, Santos ICV, Moura MAS, Segurado AC. Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin. Rev Soc Bras Med Trop 2006; 39:519-22. ^{, 7}7 . Corrêa MCJM, Barone AA, Cavalheiro NP, Tengan FM, Guastini C. Prevalence of hepatitis B and C in the sera of patients with HIV infection in São Paulo, Brasil. Rev Inst Med Trop São Paulo 2000; 42:81-5. ^{, 8}8 . Amaral ISA, Almeida ML, Alves FT, Móia LJMP, Conde SRSS. Epidemiologia de pacientes coinfectados HIV/HCV atendidos na Fundação Santa Casa de Misericórdia do Pará. Rev Para Med 2007; 21:15-24. ^{, 10}10 . Patel P, Davis S, Tolle M, Mabikwa V, Anabwani G. Prevalence of hepatites B and hepatitis C coinfections in an adult HIV centre population in Gaborone, Botswana. Am J Trop Med Hyg 2011; 85:390-4.. This explains the significant presence of drug users among the coinfected individuals (38.1%).

The findings of this study might be useful for planning activities of the Brazilian epidemiologic surveillance agencies, as well as to guide prevalence and incidence studies to obtain more detailed data to improve understanding of the HBV/HIV and HCV/HIV coinfections.

References

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