Abstract

The study investigates the survival of patients with co-infection AIDS-TB through a retrospective study of a cohort of individuals aged 13 or more and the diagnosis of AIDS reported in the years 1998-99 and following 10 years. Of the 2,091 AIDS cases, 517 (24.7%) had positive diagnosis for tuberculosis, and 379 (73.3%) were male. The risk among co-infected patients was 1,65 times the not co-infected. Have been compared the exposed and non-exposed through the Kaplan-Meier and Cox method. The variables associated with longer survival were: female gender (HR = 0.63), educational level ≥ eight years (HR = 0.52), CD4 diagnostic criteria (HR = 0.64); and shorter survival: age ≥ 60 years (HR = 2.33), no use of HAART (HR = 8.62), no investigation to Hepatitis B (HR = 2.44) and opportunistic infections ≥ two (HR = 1.97). The average survival rate, related to TB infection was 69 months for the Southeast region and 73 months for the South. AIDS and tuberculosis require monitoring and treatment adherence and they are markers of the quality of care and survival of patients in Brazil.

Key words
AIDS; Survival analysis; Tuberculosis

Introduction

The survival and evolution of AIDS patients’ clinical and laboratorial conditions improved considerably after Brazil's Health Ministry started offering Highly Active Antiretroviral Therapy (HAART) in 1996. In addition, it has been noticed a decrease in internment of people living with HIV/AIDS, as well as fewer opportunistic infections and an increase in chronic diseases, such as hepatic, cardiovascular, renal, among others¹1. Menesia EO, Passos C, Dinis A, Monteiro ME, Dal-Fabbro AL, Laprega MR. Sobrevivência de pacientes com AIDS em uma cidade do Sudeste Brasileiro. Rev Panam Salud Pública 2001; 10(1):29-36.^–55. Lima VD, Hogg RS, Harrigan PR, Moore D, Yip B, Wood E, Montaner JS. Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 2007; 21(6):685-692..

Despite the positive impact in patients’ survival, the lack of access to medication, to health care – mainly specialized assistance – and difficulties referring to treatment adhesion still have a negative impact in case outcomes, influenced by socioeconomic situation¹1. Menesia EO, Passos C, Dinis A, Monteiro ME, Dal-Fabbro AL, Laprega MR. Sobrevivência de pacientes com AIDS em uma cidade do Sudeste Brasileiro. Rev Panam Salud Pública 2001; 10(1):29-36.^,66. Padoin SMM, Zuge SS, Santos ÉEP, Primeira MR, Aldrighi JD, Paula CC. Adesão à terapia antirretroviral para HIV/AIDS. Cogitare Enferm 2013; 18(3):576-581.^,77. Pereira AGL, Matos HJ, Escosteguy CC, Marques MVRE, Medronho RA. Sobrevida de pacientes com Síndrome da Imunodeficiência Adquirida em hospital geral no Rio de Janeiro, a partir de dados da vigilância epidemiológica. Cad Saúde Colet 2013; 21(2):160-167.. Besides social and medical-assistance factors, opportunistic infections also relate to AIDS prognostic, such as tuberculosis and comorbidities.

The study on survival of people with AIDS is a way to evaluate the epidemic situation, particularly the impact of intervention policies and measures. In a cohort of patients, from south and southeast regions, diagnosed in 1998 and 1999, 59,4% of the adults survived 108 months²2. Guibu IA, Barros MBA, Donalísio MR, Tayra A, Alves MCGP. Survival of AIDS patients in the Southeast and South of Brazil: analysis of the 1998-1999 cohort. Cad Saude Publica 2011; 27(Supl. 1):S79-S92.. These estimates were greater than what have been found in a national study of notified patients from 1996, with mean survival of 58 months³3. Marins JRP, Jamal LF, Chen SY, Barros MB, Hudes ES, Barbosa AA, Chequer P, Teixeira PR, Hearst N. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS 2003; 17(11):1675-1682., and even greater if compared to estimated survival of 5,1 months back in the beginning of the epidemic, from 1982 to 1989, before the antiretroviral therapy⁸8. Chequer P, Hearst N, Hudes ES, Castilho E, Rutherford G, Loures L, Rodrigues L. Determinants of survival in adult Brazilian AIDS patients, 1982-1989. The Brazilian State AIDS Program Co-Ordinators. AIDS 1992; 6(5):483-487..

AIDS-Tuberculosis co-infection cases are often reported in several places worldwide⁹9. Santos JS, Beck ST. A coinfecção tuberculose e HIV: um importante desafio - Artigo de revisão. Rev Bras Anal Clin 2009; 41(3):209-215., particularly in regions with high prevalence of tuberculosis, reaching mainly marginalized and poor segments from society¹⁰10. Santos Neto M, Silva FL, Sousa KR, Yamamura M, Popolin MP, Arcêncio RA. Clinical and epidemiological profile and prevalence of tuberculosis/HIV co-infection in a regional health district in the state of Maranhão, Brazil. J Bras Pneumol 2012; 38(6):724-732.^,1111. Escombe AR, Moore DA, Gilman RH, Pan W, Navincopa M, Ticona E, Martínez C, Caviedes L, Sheen P, Gonzalez A, Noakes CJ, Friedland JS, Evans CA. The Infectiousness of Tuberculosis Patients Coinfected with HIV. PloS Med 2008; 5(9):e188..

The Brazil presented the highest number of tuberculosis (TB) cases in Latin America in 2013. Although a TB morbidity and mortality decrease tendency has been observed, the country¹²12. Guimarães RM, Lobo AP, Siqueira EA, Borges TFF, Melo SCC. Tuberculosis, HIV, and poverty: temporal trends in Brazil, the Americas, and worldwide. J Bras Pneumol 2012; 38(4):511-517.^–1414. Taarnhøj GA, Engsig FN, Ravn P, Johansen IS, Larsen CS, Røge B, Andersen AB, Obel N. Incidence, risk factors and mortality of tuberculosis in Danish HIV patients 1995-2007. BMC Pulm Med 2011; 11:26 presented an incidence of 46 cases per 100.000 inhabitants in that year¹⁵15. World Health Organization (WHO). WHO global tuberculosis report 2014. The burden of disease caused by TB (Chapter 2). Geneva, Switzerland; 2014. [acessado 2015 Abr 05]. Disponível em: http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf.
http://apps.who.int/iris/bitstream/10665... .

It is possible to consider that AIDS pandemic resulted in a great impact in TB epidemiology. The co-infection is of great concern due to the fact that HIV is the greatest risk factor for TB development¹⁰10. Santos Neto M, Silva FL, Sousa KR, Yamamura M, Popolin MP, Arcêncio RA. Clinical and epidemiological profile and prevalence of tuberculosis/HIV co-infection in a regional health district in the state of Maranhão, Brazil. J Bras Pneumol 2012; 38(6):724-732.^,1616. Mendes AM, Fensterseifer LM. Tuberculose: porque os pacientes abandonam o tratamento? Bol Pneumol Sanit 2004; 12(1):27-38., a disease yet to be controlled in developing countries, even there being means to diagnose and cure.

Among AIDS related diseases, TB is particularly important because it is contagious, treatable, and frequently one of the earliest clinical manifestations of immunologic deficiency. Upholds itself as one of the main AIDS defining diseases, topping pneumonia caused by Pneumocystis jiroveci since 2001 ¹⁷17. Soares ECC, Saraceni V, Lauria LM, Pacheco AG, Durovni B, Cavalcante SC. Tuberculosis as a disease defining acquired immunodeficiency syndrome: ten years of surveillance in Rio de Janeiro, Brazil. J Bras Pneumol 2006; 32(5):444-448..

There are, in Brazil, great differences in TB incidence and mortality, particularly higher in regions with greater prevalence of HIV infections ¹⁸18. Brasil. Secretaria de Vigilância em Saúde (SVS). Programa Nacional de DST e Aids. Boletim Epidemiológico 2014 - Aids e DST. Brasília: SVS; 2014.^,1919. Batista JAL, Albuquerque MFPM, Maruza M, Ximenes RAA, Santos ML, Montarroyos UR, Miranda-Filho DB, Lacerda HR, Rodrigues LC. Incidence and Risk Factors for Tuberculosis in People Living with HIV: Cohort from HIV Referral Health Centers in Recife, Brazil. PLos ONE 2013; 8:5.. Besides, AIDS-Tuberculosis co-infection is identified as an associated factor in TB internment cases ²⁰20. Perrechi MCT, Ribeiro SA. Outcomes of tuberculosis treatment among inpatients and outpatients in the city of São Paulo, Brazil. J Bras de Pneumol 2011; 37(6):783-790.. Other variables have been considered for co-infection prognostic better understanding, particularly CD4 levels in other regions of the world ¹³13. Whalen CC, Nsubuga P, Okwera A, Johnson JL, Hom DL, Michael NL, Mugerwa RD, Ellner JJ. Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda. AIDS 2000; 14(9):1219-1228.^,1414. Taarnhøj GA, Engsig FN, Ravn P, Johansen IS, Larsen CS, Røge B, Andersen AB, Obel N. Incidence, risk factors and mortality of tuberculosis in Danish HIV patients 1995-2007. BMC Pulm Med 2011; 11:26^,2121. Waitt CJ, Squire SB. A systematic review of risk factors for death in adults during and after tuberculosis treatment. Int J Tuberc Lung Dis 2011; 15(7):871-885.^,2222. Gupta A, Wood R, Kaplan R, Bekker LG, Lawn SD. Prevalent and incident tuberculosis are independent risk factors for mortality among patients accessing antiretroviral therapy in South Africa. PLos ONE 2013; 8(2):e55824..

Tuberculosis is a high prevalence disease in Brazil. However, there are few population based studies about associated factors on patient survival with co-infection and its mortality impact ⁶6. Padoin SMM, Zuge SS, Santos ÉEP, Primeira MR, Aldrighi JD, Paula CC. Adesão à terapia antirretroviral para HIV/AIDS. Cogitare Enferm 2013; 18(3):576-581.^,2323. Golub JE, Durovni B, King BS, Cavalacante SC, Pacheco AG, Moulton LH, Moore RD, Chaisson RE, Saraceni V. Recurrent tuberculosis in HIV-infected patients in Rio de Janeiro, Brazil. AIDS 2008; 22(18):2527-2533.^–2525. Saita NM, Oliveira HB. Tuberculosis, AIDS and tuberculosis-AIDS co-infection in a large city. Rev latino am enferm 2012; 20(4):769-777..

The objective of this study was to analyze patient survival time with AIDS-Tuberculosis co-infection, according to sociodemographic, epidemiologic, clinical, and health care use traits in South and Southeast regions of Brazil.

Method

This is a retrospective cohort study of medical records sample of individuals with an AIDS diagnosis of 13 years or more, reported to Notification Harm Information System (SINAN) in 1998 and 1999, with a 10-year following.

The regions studied were South and Southeast, which have populations of 29.016.114 and 85.115.623 inhabitants, and territorial area of 576.773,368 km² and 924.616,968 km², respectively²⁶26. Instituto Brasileiro de Geografia e Estatística[homepage na internet]. Censos demográficos: 2000 e 2010. Contagem Populacional: 1996. Estimativas preliminares para os anos intercensitários dos totais populacionais, estratificadas por idade e sexo pelo MS/SGEP/Datasus: 1992-1999, 2001-2006. Estimativas elaboradas no âmbito do Projeto UNFPA/IBGE (BRA/4/P31A) - População e Desenvolvimento. Coordenação de População e Indicadores Sociais: 2007-2009. Estimativas populacionais enviadas para o TCU, estratificadas por idade e sexo pelo MS/SGEP/Datasus: 2011-2012. [acessado 2015 Abr 15]. Disponível em: http://www2.datasus.gov.br/DATASUS/index.php?area=0206&id=6942
http://www2.datasus.gov.br/DATASUS/index... . The Studied cohort was assembled through sortition of cities from the regions, where there have been more than 40 cases through the year, totaling 33 and 90 cities, respectively, in the South and Southeast regions ²2. Guibu IA, Barros MBA, Donalísio MR, Tayra A, Alves MCGP. Survival of AIDS patients in the Southeast and South of Brazil: analysis of the 1998-1999 cohort. Cad Saude Publica 2011; 27(Supl. 1):S79-S92..

As a study inclusion criteria, should be pointed out the case confirmation according to current definition stated by Brazil's Health Ministry, by the time of this study conduction, that is, an adapted Center of disease control (CDC), Rio de Janeiro/Caracas, CDC Exceptional Criteria, Death Exceptional Criteria, Antiretroviral Exceptional use Criteria (ARC) + Death and T-CD4 cell count (less than 350/mm³, independent of symptoms)²⁷27. Brasil. Ministério da Saúde (MS). Critérios de definição de casos de aids em adultos e crianças. Brasília: MS; 2004.. These criteria observation was verified during medical records analysis.

Were excluded from investigation pregnant women with AIDS notifications, cases which defining criteria was death in less than seven days, cases first diagnosed because of death, ARC criteria + death and ignored criteria.

Were identified 29.600 and 8.979 cases, distributed through 90 and 33 cities in Southeast and South regions, respectively. Sample sizes planned for Southeast and South regions were of 1.484 and 898 patients. These numbers would allow to consider statistically significant differences of 5 and 9 months of median survival between groups compared in each region. An uneven sharing of the sample by strata (region) was chosen in order to lower differences between sample fractions²2. Guibu IA, Barros MBA, Donalísio MR, Tayra A, Alves MCGP. Survival of AIDS patients in the Southeast and South of Brazil: analysis of the 1998-1999 cohort. Cad Saude Publica 2011; 27(Supl. 1):S79-S92..

In each region, sampling by gathering was utilized in two stages: cities (or city groups) and patients. The sample primary units sortition was made with proportional probability to notification number. Cities that did not have a minimal notification number were grouped to larger ones.

The sample fractions were of 1/13,369 to Southeast region, and of 1/6,873 to South region, being picked 18 primary sample units in the Southeast and 10 in the South, corresponding to 14 and 9 cities, respectively. To compensate for different selection probabilities in the regions, data collected were pondered, being that the weight for each patient was given by the inverse sample fraction of the region he or she belonged.

The medical reports analysis granted registry of sociodemographic variables, skin color, schooling in years, age group; epidemiological: HIV exposure category, sexual practice, mates number. Clinical variables were also utilized, such as comorbidity presence, antiretroviral regular use, AIDS defining criteria, a cancer diagnose, opportunistic diseases. Some variables related to use and clinical follow up: presence of multiprofessional team, beyond nurses and physicians, Hepatitis B serum markers collection, TB and Pneumonia by Pneumocystis jiroveci prophylaxis, at the health care service where the patient was taken care of.

Cases were classified according to TB diagnose presence in any clinical form. To calculate survival were considered AIDS diagnosis date, death date (fail), follow up drop off (censorship) and end of study (programmed censorship)²⁹29. Kleinbaum DG, Klein M. Survival Analysis. 3th ed. New York: Springer; 2012..

The information was collected by healthcare professionals (nurses and physicians) linked to services where patients were taken care of. The information was checked by research field coordinators and revised by the research team regarding to inclusion criteria, diagnosis criteria, and data consistency concerning the study. After data compilation, data base elaboration and inconsistencies correction, the data was explored regarding patient survival with AIDS-tuberculosis co-infection and co variables of interest possibly associated to mortality.

Initially, were compared cases with or without death outcome, between groups with the co-infection or without it. The lethal coefficient in the studied population was estimated taking as numerator deaths, and as denominator the amount of individuals at the beginning of the co-infected and non co-infected cohorts followed in the study²⁸28. Szklo M, Javier Nieto F. Measuring Disease Occurrence. Epidemiology Beyond the Basics. 3th ed. Burlington: Jones & Bartlett Learning; 2014.. Pearson chi-squared association tests were utilized and Fisher exact test, when necessary, with a 5% significance. For survival analysis, it was considered as response variable time spent from AIDS notification to death or drop off event, or end of the study, the others being predictor variables.

After checking the proportionality of the selected variables by the “Log minus Log” test, the analysis of the survival curves was performed using the Kaplan-Meier method and Log-rank test²⁹29. Kleinbaum DG, Klein M. Survival Analysis. 3th ed. New York: Springer; 2012., with significance level of 5%, with accumulated survival probability in months, according to each variable of interest. To calculate hazard ratio (HR), Mantel Hanzel analysis was utilized. After univariate analysis, Cox multiple regression model was adjusted, with trust interval of 95%. It was assumed that HR for an independent analysis is proportional through time²⁹29. Kleinbaum DG, Klein M. Survival Analysis. 3th ed. New York: Springer; 2012., thus allowing inclusion of several simultaneous co variables in survival time modeling³⁰30. Cox DR. Regression models and life tables. J R Stat Soc Ser B Methodol 1972; 34(2):187-220..

For all tests of survival comparing and analysis, all “no information” categories of all study variables were ignored. For survival calculation according to skin color, whites and blacks/browns were compared, ignoring other referred categories due to reduced number of individuals. Because there were patients with more than one type of TB diagnosed, severe cases were considered of survival curve calculation related with disease clinical form.

Computer programs Microsoft Excel 2013 and Software IBM SPSS Statistics 21 for windows were utilized for statistical analysis.

The study was approved by São Paulo State Secretary`s Reference and Training in STD/AIDS Center Research Ethics Committee and by Unicamp Research Ethics Committee - Campinas Campus.

Results

Of the 2091 studied cases of 13 year old or older individuals, 517 (24.7%) had TB diagnosed with at least one of the infection clinical forms, being 379 (73.3%) males. Men/women ratio was 2,7:1 among co-infected, and 1,6:1 among not co-infected. It was noticed a higher percentage of deaths among patients that showed at least one clinical form of TB (Table 1).

As to age group, even though most cases were between 26 and 39 years old at the moment of diagnosis, no difference between co-infected and not co-infected was noticed. (Table 1).

As to referred skin color, comparing whites to blacks/browns, there was a greater share of whites among not co-infected, 853 (54.2%) (p < 0,01). Significant differences were seen with greater proportion among women, schooling greater than 8 years, sexual transmission and homossexual practice among not co-infected individuals (Table 1).

The Table 2 displays some clinical variables of use by health care services. It was noticed that a large amount of people was in regular use of ART in both groups, higher than 85%. As to diagnostic criteria for AIDS, CD4 counting, percentage among co-infected, 203 (39.3%), was inferior to not co-infected, 931 (59.1%).

Frequency of cancer diagnosis wasn't different between groups (p = 0.18), however, it was observed a greater percentage of opportunistic diseases among patients with TB diagnosis (p = 0.03) (Table 2).

Variables associated to patient follow up and access to other professionals are presented in Table 2. It was noticed that 1.020 (64.8%) of not co-infected patients received care by other professionals, not only physicians and nurses, less frequent that co-infected patients (74.3%). As to hepatitis B, there was no statistical difference in exam request. (Table 2).

Kaplan Meier survival curve analysis (Figure 1-A) suggests that co-infected patients had lower survival up to 60 months after AIDS diagnosis compared with not co-infected ones. Accumulated survival was of 70% for not co-infected and 58% for co-infected. Survival curves comparison using Log-rank (Mantel-Cox) survival distribution equality test showed a difference between groups (p < 0,01).

After adjusting Cox multiple model, accumulated survival was of 71% for co-infected and 81% for not co-infected after 60 months of diagnosis (Figure 1-B). Mean survival related to TB co-infection was of 69 months for Southeast region and 73 months for South region.

The Table 3 presents risk estimator in univariate and multiple analysis using Cox model, via stepwise. Risk among AIDS-tuberculosis co-infected was of 1.65 (IC95%: 1.30-2.08) times the not infected in multiple model.

Variables presented in positive association to greater survival were: female sex (HR = 0,63 and IC95%: 0.50–0.81), schooling greater than five years (HR = 0.68 and IC95%: 0,51–0,91), CD4 diagnosis criteria (HR = 0.64 IC95%: 0.49–0.85). Variables associated negatively with survival were: age group greater than 60 years old (HR = 2.33 IC95%: 1.13–4.84), non regular use of ART (HR = 8.62 IC95%: 6.11–12.17), no hepatitis B investigation (HR = 2.44 IC95%: 1.94–3.06), TB diagnosis (HR = 1.65 IC95%: 1.30–2.08) and two of more opportunistic diseases (HR = 1.97 IC95%: 1.46–2.66) (Table 3).

Lower accumulated survival was noticed in 60 months in patients presenting clinical form of disseminated/extrapulmonary/not cavitary TB infection (55%). Followed by cavitary pulmonary tuberculosis (58%), ganglionar/non specific TB (68%). Comparison between curves using Log-rank test showed no difference among them (p < 0,00) (Figure 2).

Discussion

This study has shown that survival of diagnosed patients in 1998 and 1999, in 10 years, was superior to patients diagnosed before this period of time⁶6. Padoin SMM, Zuge SS, Santos ÉEP, Primeira MR, Aldrighi JD, Paula CC. Adesão à terapia antirretroviral para HIV/AIDS. Cogitare Enferm 2013; 18(3):576-581.^,88. Chequer P, Hearst N, Hudes ES, Castilho E, Rutherford G, Loures L, Rodrigues L. Determinants of survival in adult Brazilian AIDS patients, 1982-1989. The Brazilian State AIDS Program Co-Ordinators. AIDS 1992; 6(5):483-487.. It was registered lethality of 46.8% and 32.5% in patients with and without co-infection, respectively (p < 0,01). In both regions, mortality among co-infected topped that of not co-infected. Groups also presented distribution differences in sociodemographic, epidemiological, clinical and health care use variables.

After 60 months of AIDS diagnosis, no difference was observed in accumulated survival between South and Southeast regions. Mortality among AIDS-tuberculosis co-infected patients was greater in both regions, 39.5% in South region and 42% in southeast region. The association between these diseases justify the statement that, in all patients with TB, HIV must be tested for. On the other hand, for every patient with HIV infection, TB must be tested⁹9. Santos JS, Beck ST. A coinfecção tuberculose e HIV: um importante desafio - Artigo de revisão. Rev Bras Anal Clin 2009; 41(3):209-215..

The amount of patients with AIDS-Tuberculosis infection was about 1/4 the population studied, 517 (24.7%). A similar co-infection percentage has been seen in a Rio de Janeiro hospital cohort⁷7. Pereira AGL, Matos HJ, Escosteguy CC, Marques MVRE, Medronho RA. Sobrevida de pacientes com Síndrome da Imunodeficiência Adquirida em hospital geral no Rio de Janeiro, a partir de dados da vigilância epidemiológica. Cad Saúde Colet 2013; 21(2):160-167.. Studies in Southeast region point to a 34.5% AIDS-tuberculosis co-infection prevalence in Belo Horizonte, MG, 52.5% in São José do Rio Preto, SP, 17.5% in Campinas, SP, and 14.5% in Vitória, ES²⁵25. Saita NM, Oliveira HB. Tuberculosis, AIDS and tuberculosis-AIDS co-infection in a large city. Rev latino am enferm 2012; 20(4):769-777.^,3131. Pedro HSP, Pereira MIF, Goloni MRA, Pires FC, Oliveira RS, da Rocha MAB, Conceição LM, Fraga VD, Fenley JC, Cordeschi T, Machado RL, Franco C, Rossit AR. Mycobacterium tuberculosis in a HIV-1-infected population from Southeastern Brazil in the HAART era. Trop Med Int Health 2011; 16(1):67-73.^–3333. Pinto Neto LFS, Vieira NFR, Cott FS, Oliveira FMA. Prevalência da tuberculose em pacientes infectados pelo vírus da imunodeficiência humana. Rev Soc Bras Clin Méd 2013; 11(2):118-122..

The infection reactivation by Mycobacterium tuberculosis due to immunity drop, as well as new infections can occur in individuals with AIDS.

Unequal distribution of deaths between co-infected and not co-infected was seen at the period, with lethality of 46.8% and 32.5%, respectively (p < 0,01). Groups also displayed distribution differences in sociodemographic, epidemiological, clinical and health care use variables.

Survival at 60 months was similar between both South (78%) and Southeast (79%) regions, given that for those with TB diagnosis, in both regions, the survival dropped at the period, even in the presence of co variables. Particularly among patients with disseminated/extrapulmonary/not cavitary TB co-infection, survival at 60 months was significantly lower, agreeing with severity and disease spread on an immunosuppressive state.

Kaplan-Meier curves, as well as multiple model, showed significant differences in patient survival with and without co-infection. TB aside, the presence of opportunistic diseases also abbreviated the studied population survival⁵5. Lima VD, Hogg RS, Harrigan PR, Moore D, Yip B, Wood E, Montaner JS. Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 2007; 21(6):685-692.^,66. Padoin SMM, Zuge SS, Santos ÉEP, Primeira MR, Aldrighi JD, Paula CC. Adesão à terapia antirretroviral para HIV/AIDS. Cogitare Enferm 2013; 18(3):576-581..

An hypothesis to explain lower survival among AIDS-Tuberculosis co-infected is TB treatment drop off due to adverse events: drug interaction from combined therapies, as well ass alcohol, smoking, opportunistic diseases, T-CD4 count lower than 200/mm³ as TB treatment drop off predictors, dealing prognostic impact to the patient¹³13. Whalen CC, Nsubuga P, Okwera A, Johnson JL, Hom DL, Michael NL, Mugerwa RD, Ellner JJ. Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda. AIDS 2000; 14(9):1219-1228.^,2424. Maruza M, Albuquerque MFPM, Coimbra I, Moura LV, Montarroyos UR, Miranda Filho DB, Lacerda HR, Rodrigues LC, Ximenes RA. Risk factors for default from tuberculosis treatment in HIV-infected individuals in the state of Pernambuco, Brazil: a prospective cohort study. BMC Infect Dis 2011; 11:351..

Cases of AIDS with or without TB diagnosis are more prevalent among males, as seen in other studies¹1. Menesia EO, Passos C, Dinis A, Monteiro ME, Dal-Fabbro AL, Laprega MR. Sobrevivência de pacientes com AIDS em uma cidade do Sudeste Brasileiro. Rev Panam Salud Pública 2001; 10(1):29-36.^–33. Marins JRP, Jamal LF, Chen SY, Barros MB, Hudes ES, Barbosa AA, Chequer P, Teixeira PR, Hearst N. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS 2003; 17(11):1675-1682.^,1919. Batista JAL, Albuquerque MFPM, Maruza M, Ximenes RAA, Santos ML, Montarroyos UR, Miranda-Filho DB, Lacerda HR, Rodrigues LC. Incidence and Risk Factors for Tuberculosis in People Living with HIV: Cohort from HIV Referral Health Centers in Recife, Brazil. PLos ONE 2013; 8:5.. The strong relation with poverty, low schooling and TB may explain the greater risk of dying among individuals up to four years of study⁶6. Padoin SMM, Zuge SS, Santos ÉEP, Primeira MR, Aldrighi JD, Paula CC. Adesão à terapia antirretroviral para HIV/AIDS. Cogitare Enferm 2013; 18(3):576-581.^,1212. Guimarães RM, Lobo AP, Siqueira EA, Borges TFF, Melo SCC. Tuberculosis, HIV, and poverty: temporal trends in Brazil, the Americas, and worldwide. J Bras Pneumol 2012; 38(4):511-517.. This variable is a socioeconomic marker of the population, even though quite frequently not available in medical records and notification files⁷7. Pereira AGL, Matos HJ, Escosteguy CC, Marques MVRE, Medronho RA. Sobrevida de pacientes com Síndrome da Imunodeficiência Adquirida em hospital geral no Rio de Janeiro, a partir de dados da vigilância epidemiológica. Cad Saúde Colet 2013; 21(2):160-167.^,99. Santos JS, Beck ST. A coinfecção tuberculose e HIV: um importante desafio - Artigo de revisão. Rev Bras Anal Clin 2009; 41(3):209-215.^,1212. Guimarães RM, Lobo AP, Siqueira EA, Borges TFF, Melo SCC. Tuberculosis, HIV, and poverty: temporal trends in Brazil, the Americas, and worldwide. J Bras Pneumol 2012; 38(4):511-517.^,3434. Villarinho MV, Padilha MI, Berardinelli LMM, Borenstein MS, Meirelles BHS, Andrade SR. Public health policies facing the epidemic of AIDS and the assistance for people with the disease. Rev Bras Enferm 2013; 66(2):271-217..

It is worth mentioning the differences found in referred skin color in AIDS-tuberculosis co-infected patients, being blacks/browns more prevalent. The use of race/referred skin color as an analytical variables has contributed to a better understanding of disadvantages and inequalities black people face when accessing proper health care resources. The study on women tested positive for HIV in São Paulo registered a vulnerability situation and little access to health care services, as well as greater schooling and comprehension difficulties about the disease and exams requested³⁵35. Lopes F, Buchalla CM, Ayres JRCM. Mulheres negras e não-negras e vulnerabilidade ao HIV/Aids no estado de São Paulo, Brasil. Rev Saude Publica 2007; 41(Supl. 2):39-46.. Although significant in univariable model and greater prevalence of black/brown patients among co-infected, this variable did not remain linked to death risk in the final multiple model after adjusting with “schooling years” variable, suggesting a greater socioeconomical condition relevance in survival, independently from referred skin color. It is worth mentioning the interpretation limitations and reliability of this information, particularly in medical records.

Worse life conditions make health care access, correct medication use comprehension, proper nutrition care and other general orientations more difficult³⁶36. Rodrigues ILA, Monteiro LL, Pacheco RHB, Silva SÉD. Abandonment of tuberculosis treatment among patinets co-infected with TB/HIV. Rev Esc Enferm USP 2010; 44(2):383-387..

A study performed in Rio de Janeiro showed that survival is strongly influenced by CD4 count above 100 cells/mm³, lowering opportunistic diseases incidence³⁷37. Gadelha AJ, Accacio N, Costa RLB, Galhardo MC, Cotrim MR, Souza RV, Morgado M, Marzochi K, Lourenço MC, Rolla VC. Morbidity and survival in advanced AIDS in Rio de Janeiro, Brazil. Rev Inst Med Trop São Paulo 2002; 44(4):179-186.. Regular use of antiretroviral medication improved considerably, 8.62 times the life expectancy in this cohort and changed the immunologic profile of patients with TB co-infection due to immunity recovery. Similar results were registered in several regions worldwide, emphasizing the greater impact of combined antiretroviral therapies (three antiretroviral usage) since year 2000 and consequent CD4 cells recovery⁵5. Lima VD, Hogg RS, Harrigan PR, Moore D, Yip B, Wood E, Montaner JS. Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 2007; 21(6):685-692.^,66. Padoin SMM, Zuge SS, Santos ÉEP, Primeira MR, Aldrighi JD, Paula CC. Adesão à terapia antirretroviral para HIV/AIDS. Cogitare Enferm 2013; 18(3):576-581.^,3838. Tancredi MV. Sobrevida de pacientes com HIV e AIDS nas eras pré e pós terapia antirretroviral de alta potência [tese]. São Paulo: Universidade de São Paulo; 2010.^–4343. Lai D, Hardy RJ. An update on the impact of HIV/AIDS on life expectancy in the United States. AIDS 2004; 18(12):1732-1734..

Some variables were included in this study with the objective of analyzing survival with patient care association, such as prophylaxis usage, hepatitis B serology request and multiprofessional care, which would indirectly indicate service adhesion, clinical follow up and integral patient management.

Among health care related variables, although associated to univariable analysis, only hepatitis B serology request remained as a greater survival predictor of patients with AIDS managed in the cities. The request of these exams denotes a treatment comprising other chronic diseases investigation, one of them being preventable and both being of clinic and therapeutic follow up.

A study evaluated the care of patients with AIDS in Brazil, emphasizing the heterogeneity of health care assistance and infrastructure, even though there are medication availability, clinical follow up exams, as well as infectology specialized physician in most services⁴⁴44. Melchior R, Nemes MI, Basso CR, Castanheira ER, Alves MT, Buchalla CM, Donini AA. Evaluation of the organizational structure of HIV/AIDS outpatient care in Brazil. Rev Saude Publica 2006; 40(1):143-151..

Although prophylaxis with isoniazida has reduced TB active infection in individuals with AIDS, treatment adhesion, drug resistance and toxicity have limited this high risk measure. Integrated care and decentralization of preventive actions, screening and TB treatment for people living with HIV can reduce co-infection and limit drug resistance.

A few limitations in this study can be evidenced, such as the quality of registered information in medical records, which are not always reliable and may vary in different regions of the country. The 10 year analysis from past decade (1998-2008) may not reflect the epidemic dynamic nowadays, considering changes in patient profiles like age group, decrease in injecting drug users, availability of new antiretroviral drugs and more powerful and easier to use associations. However, it is a population based study with survival estimates which contribute to registration of parameters and post-HAART epidemic indicators, relevant to monitoring the disease in Brazil.

Conclusions

Patient survival post-HAART has increased among patients studied. These results show the investments made by STD/AIDS national, state and municipal programs, aiming universal access to treatment and clinical follow up of patients with AIDS. Despite advancements in policies and health care service to affected individuals, some challenges remain, such as overcoming inequalities related to early diagnosis and availability and adhesion to treatment for both AIDS and TB. AIDS and TB are two chronic diseases that demand clinical follow up and adhesion to treatment and can be analyzed as marker of difficulties to overcoming limitations still existing in patient survival in Brazil.

Acknowledgment

The research was funded by the Foundation for Research Support of the State of São Paulo (FAPESP) and the National STD-AIDS Program with resources of the United Nations Educational, Scientific and Cultural Organization (UNESCO).

References

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