Mortality profiles among people living with HIV/AIDS: comparison between Rio de Janeiro and other federative units between 1999 and 2015

Adelzon Assis de Paula Denise Franqueira Pires Pedro Alves Filho Katia Regina Valente de Lemos Valdiléa Gonçalves Veloso Beatriz Grinsztejn Antonio Guilherme Pacheco About the authors

ABSTRACT:

Introduction:

The trend toward stabilization regarding the AIDS epidemic in Brazil over the past decade hides a very complex scenario, where two-thirds of the Brazilian federative units exhibit AIDS standardized mortality rates (ASMR) significantly above the national average and/or in upward tendency. ASMR in Rio de Janeiro State remains virtually unchanged over the years; the state currently occupies the second position in the national ranking of this indicator.

Objective:

To assess temporal trends in causes of death searching for differential profiles that could be useful for understanding mortality among patients with HIV in the state.

Methodology:

Causes of death were analyzed in any field of the death certificates from the Mortality Information System between 1999 and 2015 for individuals ≥ 15 years of age. Cardiovascular diseases, non-AIDS-related cancers, external causes, diabetes mellitus, and tuberculosis were established by the mention or not of their codes according to the 10th edition of International Statistical Classification of Diseases and Related Health Problems (ICD-10) in death certificates. Generalized linear mixed-effects models were used to describe odds ratios in relation to 1999 and adjusted mean annual variations.

Results:

The results point to the emerging role of external causes and genitourinary diseases and the persistent role played by tuberculosis, differentially affecting AIDS mortality in the state, in a scenario of high mortality due to infectious diseases.

Conclusion:

These data suggest that tuberculosis remains a major cause of death among people living with HIV/AIDS (PLWHA) in Rio de Janeiro, highlighting the need for studies that identify individual-level factors impacting their survival, thus improving local HIV/AIDS control measures.

Keywords:
Acquired immunodeficiency syndrome; Mortality; Tuberculosis; Time series studies

INTRODUCTION

Globally, the morbimortality profile of people living with HIV/AIDS (PLWHA) has been changing in the combination antiretroviral therapy (cART) era, as a consequence of the decreasing incidence of AIDS-associated events and increased survival of these patients11. Luz PM, Bruyand M, Ribeiro S, Bonnet F, Moreira RI, Hessamfar M, et al. AIDS and non-AIDS severe morbidity associated with hospitalizations among HIV-infected patients in two regions with universal access to care and antiretroviral therapy, France and Brazil, 2000-2008: hospital-based cohort studies. BMC Infect Dis 2014; 14: 278. http://doi.org/10.1186/1471-2334-14-278
https://doi.org/http://doi.org/10.1186/1...
,22. Tancredi MV, Waldman EA. Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: a cohort study. BMC Infect Dis 2014; 14: 599. http://doi.org/10.1186/s12879-014-0599-8
https://doi.org/http://doi.org/10.1186/s...
.

Brazil was the first developing country to provide universal and free cART, offering first-line antiretroviral drugs to all eligible PLWHA since 199633. Brasil. Lei nº 9.313, de 13 de novembro de 1996. Dispõe sobre a distribuição gratuita de medicamentos aos portadores do HIV e doentes de AIDS [Internet]. Brasília; 1996 [acessado em 2 fev. 2018]. Disponível em: Disponível em: http://www2.camara.leg.br/legin/fed/lei/1996/lei-9313-13-novembro-1996-349070-publicacaooriginal-1-pl.html
http://www2.camara.leg.br/legin/fed/lei/...
. Given its magnitude, it was expected that the initiative would provide the country with benefits comparable to those found in developed regions44. Marins JR, Jamal LF, Chen SY, Barros MB, Hudes ES, Barbosa AA, et al. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS 2003; 17(11): 1675-82. https://doi.org/10.1097/00002030-200307250-00012
https://doi.org/https://doi.org/10.1097/...
.

Despite the success initially achieved, the Brazilian initiative has shown increasing signs of exhaustion, especially in the context of inequality in the implementation of HIV-response as a whole55. Grangeiro A, Escuder MM, Castilho EA. The AIDS epidemic in Brazil and differences according to geographic region and health services supply. Cad Saúde Pública 2010; 26(12): 2355-67. http://dx.doi.org/10.1590/S0102-311X2010001200014
https://doi.org/http://dx.doi.org/10.159...
. As a result, AIDS mortality in the country has tended to stabilize, as evidenced by virtually unchanged AIDS standardized mortality rates (ASMR) since 200766. Brasil. Ministério da Saúde. Boletim Epidemiológico HIV/AIDS [Internet]. Brasília; 2015 [acessado em 21 mar. 2018]. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2015/boletim-epidemiologico-hivaids-2015
http://www.aids.gov.br/pt-br/pub/2015/bo...
. Additionally, this scenario of national stability conceals a complex epidemiological situation, in which all of the country’s macro-regions present an increase in ASMR, except the Southeast77. Teixeira TR, Gracie R, Malta MS, Bastos FI. Social geography of AIDS in Brazil: identifying patterns of regional inequalities. Cad Saúde Pública 2014; 30(2): 259-71. http://doi.org/10.1590/0102-311X00051313
https://doi.org/http://doi.org/10.1590/0...
,88. Brasil. Ministério da Saúde. Boletim Epidemiológico HIV/AIDS [Internet]. Brasília; 2017 [acessado em 9 fev. 2018]. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2017/boletim-epidemiologico-hivaids-2017
http://www.aids.gov.br/pt-br/pub/2017/bo...
.

At present, two-thirds of the federative units display ASMR above the national average or at upward trend, despite the national expansion of antiretroviral coverage66. Brasil. Ministério da Saúde. Boletim Epidemiológico HIV/AIDS [Internet]. Brasília; 2015 [acessado em 21 mar. 2018]. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2015/boletim-epidemiologico-hivaids-2015
http://www.aids.gov.br/pt-br/pub/2015/bo...
. These regional and even local distinctions pose additional challenges to control policies regarding the homogeneity of the reduction in AIDS mortality among the different federative units99. Reis AC, Santos EM, Cruz MM. A mortalidade por AIDS no Brasil: um estudo exploratório de sua evolução temporal. Epidemiol Serv Saúde 2007; 16(3): 195-205. http://doi.org/10.5123/S1679-49742007000300006
https://doi.org/http://doi.org/10.5123/S...
.

Changes in mortality profile among PLWHA in Brazil were first reported by our group, characterized by the emergence of diabetes mellitus and cardiovascular disease as causes of death in this subpopulation in contrast to the general population1010. Pacheco AG, Tuboi SH, Faulhaber JC, Harrison LH, Schechter M. Increase in non-AIDS related conditions as causes of death among HIV-infected individuals in the HAART era in Brazil. PLoS One 2008; 3(1): e1531. http://doi.org/10.1371/journal.pone.0001531
https://doi.org/http://doi.org/10.1371/j...
. More recently, we restated and expanded these results by highlighting the proportional increase in cancers not related to HIV/AIDS and external causes, as well as the persistence of tuberculosis in PLWHA mortality in the country1111. Paula AA, Schechter M, Tuboi SH, Faulhaber JC, Luz PM, Veloso VG, et al. Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: an analysis of nationwide data. PLoS One 2014; 9(4): e94636. http://doi.org/10.1371/journal.pone.0094636
https://doi.org/http://doi.org/10.1371/j...
.

Rio de Janeiro, consonant with the entire country, has been showing a reduction in the proportion of deaths related to HIV/AIDS and a consequent increase in the participation of chronic conditions and external causes in mortality among PLWHA1212. Pacheco AG, Tuboi SH, May SB, Moreira LF, Ramadas L, Nunes EP, et al. Temporal changes in causes of death among HIV-infected patients in the HAART era in Rio de Janeiro, Brazil. J Acquir Immune Defic Syndr 2009; 51(5): 624-30. http://doi.org/10.1097/QAI.0b013e3181a4ecf5
https://doi.org/http://doi.org/10.1097/Q...
. However, ASMR in the state remains considerably above the averages calculated for the country and the Southeast Region since 20041313. Brasil. Ministério da Saúde. Indicadores e dados básicos do HIV/aids nos municípios brasileiros [Internet]. Brasília: Ministério da Saúde; 2018 [acessado em 20 abr. 2017]. Disponível em: Disponível em: http://indicadores.aids.gov.br/
http://indicadores.aids.gov.br/...
. In 2015, ASMR in the state was 8.7/100 thousand inhabitants, largely outnumbering the national average, estimated at 5.6/100 thousand inhabitants, occupying the second place in the national ranking, together with Amazonas State88. Brasil. Ministério da Saúde. Boletim Epidemiológico HIV/AIDS [Internet]. Brasília; 2017 [acessado em 9 fev. 2018]. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2017/boletim-epidemiologico-hivaids-2017
http://www.aids.gov.br/pt-br/pub/2017/bo...
.

Examining the temporal trends in the proportions of causes of death related and not related to HIV/AIDS among PLWHA in Rio de Janeiro and comparing these findings with those found for other federative units may reveal differential patterns that contribute to the understanding of maintaining high rates of AIDS mortality in the state.

The present work aimed to analyze the death profile among PLWHA in Rio de Janeiro in contrast to those verified for the other federative units in the context of their ASMR between 1999 and 2015.

METHODOLOGY

DATA SOURCES AND INCLUSION CRITERIA

Data were obtained from the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM). All death certificates (DC) issued between 1999 and 2015 to individuals³ 15 years old were included, as previously proposed1414. Fazito E, Vasconcelos AM, Pereira MG, Rezende DF. Trends in non-AIDS-related causes of death among adults with HIV/AIDS, Brazil, 1999 to 2010. Cad Saúde Pública 2013; 29(8): 1644-53. http://doi.org/10.1590/0102-311X00128912
https://doi.org/http://doi.org/10.1590/0...
.

DATA TABULATION

Files were obtained in DBC format and later converted to CSV format using TabWin. Codes for causes of death according to the 10th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) were extracted from DC with the aid of a Python algorithm. Tabulated variables included the number of DC, sociodemographic characteristics (date of birth, ethnic group, gender, education, place of birth, and marital status), information on death (date, federative unit [Unidade Federada - UF] of death registration and ICD-10 codes).

OUTCOMES OF INTEREST

Outcomes of interest were defined according to whether or not their corresponding ICD-10 codes were mentioned in any field of DC: cardiovascular diseases (CVD), non-HIV/AIDS-related cancers (CA), external causes (EC), diabetes mellitus (DM), genitourinary diseases (GEN), and tuberculosis (TB) (Figure 1).

Figure 1.
Definition of outcomes and study groups with respective codes of the International Statistical Classification of Diseases and Related Health Problems (ICD-10)

STATISTICAL ANALYSES

Crude and standardized mortality rates were calculated by UF and by region. Deaths were defined as the mention of the conditions of interest in any field of DC. Age standardization was performed using the reference population of the World Health Organization (WHO).

UFs were categorized according to their AIDS standardized mortality rates (ASMR) trends, calculated as the average annual variation obtained by Poisson models and generalized additive models. Such grouping was adopted given the great intraregional heterogeneity of AIDS mortality77. Teixeira TR, Gracie R, Malta MS, Bastos FI. Social geography of AIDS in Brazil: identifying patterns of regional inequalities. Cad Saúde Pública 2014; 30(2): 259-71. http://doi.org/10.1590/0102-311X00051313
https://doi.org/http://doi.org/10.1590/0...
,88. Brasil. Ministério da Saúde. Boletim Epidemiológico HIV/AIDS [Internet]. Brasília; 2017 [acessado em 9 fev. 2018]. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2017/boletim-epidemiologico-hivaids-2017
http://www.aids.gov.br/pt-br/pub/2017/bo...
and the low number of cases presented by some states.

Trends for a selected group of death causes were assessed for individuals who had B20-B24 codes mentioned in the DC (HIV group; Figure 1). On the other hand, the non-HIV group was composed of individuals whose DC did not mention such codes.The age ranges adopted were 15-29, 30-39, 40-49, 50-59, ≥ 60 years old and unknown, according to the cutoff presented in the WHO reference population. The covariates of interest were HIV/AIDS status, calendar year and region. Age and gender were used to control confounding.

Generalized linear mixed models (GLMM) were adjusted as previously described1010. Pacheco AG, Tuboi SH, Faulhaber JC, Harrison LH, Schechter M. Increase in non-AIDS related conditions as causes of death among HIV-infected individuals in the HAART era in Brazil. PLoS One 2008; 3(1): e1531. http://doi.org/10.1371/journal.pone.0001531
https://doi.org/http://doi.org/10.1371/j...
,1111. Paula AA, Schechter M, Tuboi SH, Faulhaber JC, Luz PM, Veloso VG, et al. Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: an analysis of nationwide data. PLoS One 2014; 9(4): e94636. http://doi.org/10.1371/journal.pone.0094636
https://doi.org/http://doi.org/10.1371/j...
. Briefly, the year of death was treated either as a continuous or a categorical variable. In the first case, linear trends were described as the average per year variation, while in the second, odds ratios (OR) were used to compare the annual variation in relation to 1999.

The difference between the slopes of the lines for the HIV and non-HIV groups was represented by ∆; its statistical significance, which indicates differential accelerations or decelerations, was assessed by means of an interaction term between the HIV/AIDS and calendar year variables. To assess whether ∆ presented distinctions between regions, an interaction term was inserted between the HIV/AIDS status, calendar year and region variables.

All analyses were performed in the R software environment for Windows version 3.3.1, by means of the packages lme4 for estimation of mixed models and epiTools for standardized mortality rates calculation. The project was approved by the Research Ethics Committee of the Escola Nacional de Saúde Pública Sérgio Arouca under number 1.172.797.

RESULTS

ASMR remained virtually unchanged between 1999 and 2015 in both the country and Rio de Janeiro, with adjusted average annual variations of -0.7 and -0.9%, respectively. Similar trends were observed for Santa Catarina, Mato Grosso do Sul, Distrito Federal, Mato Grosso, Minas Gerais, Acre, and Roraima (stable region - STB). Rondônia, Amazonas, Pará, Amapá, Tocantins, Maranhão, Piaui, Ceará, Rio Grande do Norte, Paraiba, Pernambuco, Alagoas, Bahia, Sergipe, Espírito Santo, Paraná, Rio Grande do Sul, and Goiás presented an upward trend in AIDS mortality (ascending region - ASC), while only São Paulo showed a clearly decreasing trend in AIDS mortality.

Mean adjusted annual variations of ASMR did not differ when the analyses included proportional redistribution of deaths with ill-defined causes (codes R00-R99) considering all causes of death.

The temporal evolution of EC among PLWHA in Rio de Janeiro has been occurring indistinctly to the process verified for STB and São Paulo; on the other hand, the trend observed for the state differed significantly from that observed for the region with ascending ASMR (p <0.001; Table 1 and Figure 2). Similarly, the trend of GEN mortality among PLWHA in Rio de Janeiro differed from the trend observed for the set of upward ASMR states, which presented a significantly higher differential adjusted mean annual variation when compared to Rio de Janeiro (3 against 1%, respectively, p <0.05; Table 1).

Table 1.
Mean adjusted annual variations for mentioning different outcomes in death certificates categorized by region between 1999 and 2015.

Figure 2.
Odds ratios (OR) and 95% confidence intervals (95%CI) comparing the chance of mentioning external causes, genitourinary diseases, and tuberculosis in death certificates over the years among different regions. Year as categorical variable; 1999 used as a reference.

As for CVD, CA and DM, ∆ did not show significant differences among regions, indicating the occurrence of similar temporal profiles for these conditions (Table 1).

The HIV group in Rio de Janeiro presented the highest adjusted annual mean variation for the mention of TB among those analyzed (3% compared to -4, 1, and 1% for São Paulo, ASC and STB, respectively). On the other hand, TB in the non-HIV group in Rio de Janeiro presented the lowest annual reduction (-1%) compared to -4, -3, and -4%, respectively for São Paulo, ASC and STB. The ∆ reached statistical significance only when Rio de Janeiro was contrasted with São Paulo (p <0.001; Table 1).

Lastly, the analysis of mortality rates according to the ICD-10 clusters revealed that HIV/AIDS-related diseases still constitute the leading cause of death among PLWHA in all regions considered (Figure 3).

Figure 3.
Mortality rates of people living with HIV/AIDS (PLWHA) per groups of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) between 1999 and 2015.

DISCUSSION

Results show the proportional increase of external causes and genitourinary diseases and, mainly, the persistent role played by TB as a cause of death, affecting differentially on AIDS mortality in Rio de Janeiro, which has been unacceptably above the national average. Interestingly, São Paulo has shown a sustained decline in TB and AIDS mortality rates over time, indicating that the state is in a far more favorable situation than Rio de Janeiro in terms of controlling both epidemics.

Despite the substantial decrease in the incidence of opportunistic diseases that followed the implementation of cART in different economic contexts globally1616. Crabtree-Ramírez B, Caro-Vega Y, Shepherd BE, Grinsztejn B, Wolff M, Cortes CP, et al. Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America. PLoS One 2016; 11(6): e0153921. http://doi.org/10.1371/journal.pone.0153921
https://doi.org/http://doi.org/10.1371/j...
, infections are still the leading cause of mortality among PLWHA in Brazil1717. Coelho LE, Cardoso SW, Amancio RT, Moreira RI, Ribeiro SR, Coelho AB, et al. Predictors of opportunistic illnesses incidence in post combination antiretroviral therapy era in an urban cohort from Rio de Janeiro, Brazil. BMC Infect Dis 2016; 16: 134. http://doi.org/10.1186/s12879-016-1462-x
https://doi.org/http://doi.org/10.1186/s...
. Accordingly, the analysis of the specific components of mortality confirms the protagonism of infectious diseases among PLWHA in the country.

We recently described TB maintenance as a cause of mortality among PLWHA nationwide1111. Paula AA, Schechter M, Tuboi SH, Faulhaber JC, Luz PM, Veloso VG, et al. Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: an analysis of nationwide data. PLoS One 2014; 9(4): e94636. http://doi.org/10.1371/journal.pone.0094636
https://doi.org/http://doi.org/10.1371/j...
. This infection remains one of the most important causes of death among PLWHA across the globe, especially in developing regions1818. Kunii O, Yassin MA, Wandwalo E. Investing to end epidemics: the role of the Global Fund to control TB by 2030. Trans R Soc Trop Med Hyg 2016; 110(3): 153-4. http://doi.org/10.1093/trstmh/trw005
https://doi.org/http://doi.org/10.1093/t...
, having a major impact on the survival of patients with HIV in Brazil as a whole1919. Moreira RC, Pacheco AG, Paula A, Cardoso SW, Moreira RI, Ribeiro SR, et al. Diabetes mellitus is associated with increased death rates among HIV-infected patients in Rio de Janeiro, Brazil. In: International AIDS Conference, 20., 2014, Melbourne. Procedures. Melbourne; 2014. and even more notably in Rio de Janeiro2020. Saraceni V, Durovni B, Cavalcante SC, Cohn S, Pacheco AG, Moulton LH, et al. Survival of HIV patients with tuberculosis started on simultaneous or deferred HAART in the THRio cohort, Rio de Janeiro, Brazil. Braz J Infect Dis 2014; 18(5): 491-5. http://doi.org/10.1016/j.bjid.2014.02.004
https://doi.org/http://doi.org/10.1016/j...
.

Presented data show that the persistence of TB in PLWHA in Rio de Janeiro is similar to what has been demonstrated collectively in the states showing an increase in AIDS mortality. Importantly, the average annual reduction in TB among the general population of Rio de Janeiro was lower than in other regions, showing that this cause of death remains virtually unchanged in the population throughout the state.

In accordance with phenomenon described herein, the analysis of a PLWHA cohort in Rio de Janeiro evidenced that at least 10% of newly diagnosed AIDS patients presented for HIV care with active TB, thus not taking advantage from preventive therapy with isoniazid, which has been shown to reduce the risk of TB isolated or in combination with death among HIV-infected patients with access to cART2121. Durovni B, Saraceni V, Moulton LH, Pacheco AG, Cavalcante SC, King BS, et al. Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomised trial. Lancet Infect Dis 2013; 13(10): 852-8. http://doi.org/10.1016/S1473-3099(13)70187-7
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.

Reporting of infections and invasive bacterial diseases as the immediate cause of death in almost half of TB/HIV co-infected patients in Rio de Janeiro2222. Silva Escada RO, Velasque L, Ribeiro SR, Cardoso SW, Marins LMS, Grinsztejn E, et al. Mortality in patients with HIV-1 and tuberculosis co-infection in Rio de Janeiro, Brazil - associated factors and causes of death. BMC Infect Dis 2017; 17: 373. http://doi.org/10.1186/s12879-017-2473-y
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suggests that these individuals could benefit from measures such as increased anti-pneumococcal immunization and the use of cotrimoxazole, as well as actions aimed primarily at TB control, such as improved screening with skin testing and preventive therapy.

The proportional increase described for GEN among PLWHA that we described complies with previous national research, in which this trend was attributed to the higher frequency of renal failure among HIV-infected individuals in contrast to the general population1414. Fazito E, Vasconcelos AM, Pereira MG, Rezende DF. Trends in non-AIDS-related causes of death among adults with HIV/AIDS, Brazil, 1999 to 2010. Cad Saúde Pública 2013; 29(8): 1644-53. http://doi.org/10.1590/0102-311X00128912
https://doi.org/http://doi.org/10.1590/0...
. Here, the differential increase of GEN among PLWHA in Rio de Janeiro was evidenced, although this finding does not contribute to the understanding of the high AIDS mortality in the state due to the low rate at which these conditions occur. The same is true regarding external causes.

Possible bottlenecks for reducing AIDS mortality in Rio de Janeiro include late presentation to clinical care for HIV - largely attributed to delayed diagnosis of infection and associated with increased risk of clinical events and progression to death, as well as reduction in the effectiveness of cART2323. Martin DA, Luz PM, Lake JE, Clark JL, Veloso VG, Moreira RI, et al. Improved virologic outcomes over time for HIV-infected patients on antiretroviral therapy in a cohort from Rio de Janeiro, 1997-2011. BMC Infect Dis 2014; 14: 322. http://doi.org/10.1186/1471-2334-14-322
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.

Although at a frequency comparable to that described for developed regions, 54% of participants in a PLWHA cohort in Rio de Janeiro presented for clinical care with a CD4 count < 350 cells/mm3, that is, with immediate recommendation to start antiretroviral therapy2424. Moreira RI, Luz PM, Struchiner CJ, Morgado M, Veloso VG, Keruly JC, et al. Immune Status at Presentation for HIV Clinical Care in Rio de Janeiro and Baltimore. J Acquir Immune Defic Syndr 2011; 57: S171-8. http://doi.org/10.1097/QAI.0b013e31821e9d59
https://doi.org/http://doi.org/10.1097/Q...
.

Although the proportion of late presentation in Rio de Janeiro does not differ from that observed nationwide2525. Souza Jr. PR, Szwarcwald CL, Castilho EA. Delay in introducing antiretroviral therapy in patients infected by HIV in Brazil, 2003-2006. Clinics 2007; 62(5): 579-84. http://doi.org/10.1590/S1807-59322007000500008
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, this picture is particularly worrying in the state, a large urban center marked by the fragmented and inefficient structure of its health system, which clearly reduces the capacity of its public health system to diagnose, treat and retain these patients in clinical care for HIV2424. Moreira RI, Luz PM, Struchiner CJ, Morgado M, Veloso VG, Keruly JC, et al. Immune Status at Presentation for HIV Clinical Care in Rio de Janeiro and Baltimore. J Acquir Immune Defic Syndr 2011; 57: S171-8. http://doi.org/10.1097/QAI.0b013e31821e9d59
https://doi.org/http://doi.org/10.1097/Q...
.

In this context, the fragmentation of the public health system and the overburden on specialized services found in Rio de Janeiro2626. Zambenedetti G, Silva RAN da. Descentralização da atenção em HIV-Aids para a atenção básica: tensões e potencialidades. Physis 2016; 26(3): 785-806. http://doi.org/10.1590/s0103-73312016000300005
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pose limitations to HIV testing, the prompt linkage of infected people to health services and their retention in continuous care, critical steps for optimization of the benefits of antiretroviral therapy and the mitigation of AIDS mortality.

Another relevant aspect regarding the issue of AIDS mortality in Rio de Janeiro, as evidenced in its capital city, is the growing proportion of patients whose HIV diagnosis is made in urgent and emergency care systems, many of whom are already showing pronounced immunodeficiency and evolving to death without prior testing2727. Saraceni V, Cruz MM da, Lauria L de M, Durovni B. Trends and characteristics of AIDS mortality in the Rio de Janeiro city after the introduction of highly active antiretroviral therapy. Braz J Infect Dis 2005; 9(3): 209-15. http://doi.org/10.1590/S1413-86702005000300003
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.

Although the proportion of deaths with ill-defined causes has been declining in the country, its value remains relatively high in most states2828. Cunha CC, Teixeira R, França E. Avaliação da investigação de óbitos por causas mal definidas no Brasil em 2010. Epidemiol Serv Saúde 2017; 26(1): 19-30. http://doi.org/10.5123/S1679-49742017000100003
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. As a result, complementary analyzes were performed by redistributing these deaths, aiming to minimize their potential impact on the ASMR; however, the variations obtained were only marginal. GLMM was chosen to be used in the analysis, adopting the states with random effects to account for any sources of variability at this level.

One of the positive aspects of the study is the evaluation of all DC issued in the national territory over a period of 15 years, which made it possible to contrast the temporal trends in causes of death for individuals with HIV/AIDS codes to those verified for individuals without such mention, as well as to compare the profiles obtained for the different Brazilian states.

Limitations of the study include the potential underweighting of the HIV/AIDS group, since B20-B24 codes are not reported in at least 25% of DC issued to HIV-infected patients, as noted among participants in two large urban cohorts of PVHA2929. Pacheco AG, Saraceni V, Tuboi SH, Lauria LM, Moulton LH, Faulhaber JC, et al. Estimating the extent of underreporting of mortality among HIV-infected individuals in Rio de Janeiro, Brazil. AIDS Res Hum Retroviruses 2011; 27(1): 25-8. http://doi.org/10.1089/aid.2010.0089
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. Other limitations include the low accuracy of DC and the influence of unrecognized confounding variables typical of population-based studies.

The findings described here need to be consolidated by approaches at individual level, examining potential factors that differentially impact the survival of these patients, in order to substantiate public policies aimed at addressing the HIV/AIDS epidemic in the state.

In conclusion, TB persistence and high infectious disease mortality rates play a central role in AIDS mortality in Rio de Janeiro and may reflect delays in identifying HIV infection and/or presenting for care and treatment. The strategy of testing and treatment seems to be insufficient by bumping into clear gaps such as the fragility of the public health system, highlighting the need for structural changes to deal more effectively with the epidemic in the state.

CONCLUSION

GEN, EC and especially TB have been differentially affecting the survival of HIV patients in Rio de Janeiro in a scenario of high occurrence of infectious diseases, a finding that supports the need to improve control measures specific to the HIV/AIDS epidemic, in parallel with the restructuring of the public health system in Rio de Janeiro.

References

  • 1
    Luz PM, Bruyand M, Ribeiro S, Bonnet F, Moreira RI, Hessamfar M, et al. AIDS and non-AIDS severe morbidity associated with hospitalizations among HIV-infected patients in two regions with universal access to care and antiretroviral therapy, France and Brazil, 2000-2008: hospital-based cohort studies. BMC Infect Dis 2014; 14: 278. http://doi.org/10.1186/1471-2334-14-278
    » https://doi.org/http://doi.org/10.1186/1471-2334-14-278
  • 2
    Tancredi MV, Waldman EA. Survival of AIDS patients in Sao Paulo-Brazil in the pre- and post-HAART eras: a cohort study. BMC Infect Dis 2014; 14: 599. http://doi.org/10.1186/s12879-014-0599-8
    » https://doi.org/http://doi.org/10.1186/s12879-014-0599-8
  • 3
    Brasil. Lei nº 9.313, de 13 de novembro de 1996. Dispõe sobre a distribuição gratuita de medicamentos aos portadores do HIV e doentes de AIDS [Internet]. Brasília; 1996 [acessado em 2 fev. 2018]. Disponível em: Disponível em: http://www2.camara.leg.br/legin/fed/lei/1996/lei-9313-13-novembro-1996-349070-publicacaooriginal-1-pl.html
    » http://www2.camara.leg.br/legin/fed/lei/1996/lei-9313-13-novembro-1996-349070-publicacaooriginal-1-pl.html
  • 4
    Marins JR, Jamal LF, Chen SY, Barros MB, Hudes ES, Barbosa AA, et al. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS 2003; 17(11): 1675-82. https://doi.org/10.1097/00002030-200307250-00012
    » https://doi.org/https://doi.org/10.1097/00002030-200307250-00012
  • 5
    Grangeiro A, Escuder MM, Castilho EA. The AIDS epidemic in Brazil and differences according to geographic region and health services supply. Cad Saúde Pública 2010; 26(12): 2355-67. http://dx.doi.org/10.1590/S0102-311X2010001200014
    » https://doi.org/http://dx.doi.org/10.1590/S0102-311X2010001200014
  • 6
    Brasil. Ministério da Saúde. Boletim Epidemiológico HIV/AIDS [Internet]. Brasília; 2015 [acessado em 21 mar. 2018]. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2015/boletim-epidemiologico-hivaids-2015
    » http://www.aids.gov.br/pt-br/pub/2015/boletim-epidemiologico-hivaids-2015
  • 7
    Teixeira TR, Gracie R, Malta MS, Bastos FI. Social geography of AIDS in Brazil: identifying patterns of regional inequalities. Cad Saúde Pública 2014; 30(2): 259-71. http://doi.org/10.1590/0102-311X00051313
    » https://doi.org/http://doi.org/10.1590/0102-311X00051313
  • 8
    Brasil. Ministério da Saúde. Boletim Epidemiológico HIV/AIDS [Internet]. Brasília; 2017 [acessado em 9 fev. 2018]. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2017/boletim-epidemiologico-hivaids-2017
    » http://www.aids.gov.br/pt-br/pub/2017/boletim-epidemiologico-hivaids-2017
  • 9
    Reis AC, Santos EM, Cruz MM. A mortalidade por AIDS no Brasil: um estudo exploratório de sua evolução temporal. Epidemiol Serv Saúde 2007; 16(3): 195-205. http://doi.org/10.5123/S1679-49742007000300006
    » https://doi.org/http://doi.org/10.5123/S1679-49742007000300006
  • 10
    Pacheco AG, Tuboi SH, Faulhaber JC, Harrison LH, Schechter M. Increase in non-AIDS related conditions as causes of death among HIV-infected individuals in the HAART era in Brazil. PLoS One 2008; 3(1): e1531. http://doi.org/10.1371/journal.pone.0001531
    » https://doi.org/http://doi.org/10.1371/journal.pone.0001531
  • 11
    Paula AA, Schechter M, Tuboi SH, Faulhaber JC, Luz PM, Veloso VG, et al. Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: an analysis of nationwide data. PLoS One 2014; 9(4): e94636. http://doi.org/10.1371/journal.pone.0094636
    » https://doi.org/http://doi.org/10.1371/journal.pone.0094636
  • 12
    Pacheco AG, Tuboi SH, May SB, Moreira LF, Ramadas L, Nunes EP, et al. Temporal changes in causes of death among HIV-infected patients in the HAART era in Rio de Janeiro, Brazil. J Acquir Immune Defic Syndr 2009; 51(5): 624-30. http://doi.org/10.1097/QAI.0b013e3181a4ecf5
    » https://doi.org/http://doi.org/10.1097/QAI.0b013e3181a4ecf5
  • 13
    Brasil. Ministério da Saúde. Indicadores e dados básicos do HIV/aids nos municípios brasileiros [Internet]. Brasília: Ministério da Saúde; 2018 [acessado em 20 abr. 2017]. Disponível em: Disponível em: http://indicadores.aids.gov.br/
    » http://indicadores.aids.gov.br/
  • 14
    Fazito E, Vasconcelos AM, Pereira MG, Rezende DF. Trends in non-AIDS-related causes of death among adults with HIV/AIDS, Brazil, 1999 to 2010. Cad Saúde Pública 2013; 29(8): 1644-53. http://doi.org/10.1590/0102-311X00128912
    » https://doi.org/http://doi.org/10.1590/0102-311X00128912
  • 15
    Heller GZ. Generalized Linear Mixed Models: Modern Concepts, Methods and Applications. By WW Stroup. Aust N Z J Stat 2013; 55(2): 197-8. http://doi.org/10.1111/anzs.12021
    » https://doi.org/http://doi.org/10.1111/anzs.12021
  • 16
    Crabtree-Ramírez B, Caro-Vega Y, Shepherd BE, Grinsztejn B, Wolff M, Cortes CP, et al. Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America. PLoS One 2016; 11(6): e0153921. http://doi.org/10.1371/journal.pone.0153921
    » https://doi.org/http://doi.org/10.1371/journal.pone.0153921
  • 17
    Coelho LE, Cardoso SW, Amancio RT, Moreira RI, Ribeiro SR, Coelho AB, et al. Predictors of opportunistic illnesses incidence in post combination antiretroviral therapy era in an urban cohort from Rio de Janeiro, Brazil. BMC Infect Dis 2016; 16: 134. http://doi.org/10.1186/s12879-016-1462-x
    » https://doi.org/http://doi.org/10.1186/s12879-016-1462-x
  • 18
    Kunii O, Yassin MA, Wandwalo E. Investing to end epidemics: the role of the Global Fund to control TB by 2030. Trans R Soc Trop Med Hyg 2016; 110(3): 153-4. http://doi.org/10.1093/trstmh/trw005
    » https://doi.org/http://doi.org/10.1093/trstmh/trw005
  • 19
    Moreira RC, Pacheco AG, Paula A, Cardoso SW, Moreira RI, Ribeiro SR, et al. Diabetes mellitus is associated with increased death rates among HIV-infected patients in Rio de Janeiro, Brazil. In: International AIDS Conference, 20., 2014, Melbourne. Procedures. Melbourne; 2014.
  • 20
    Saraceni V, Durovni B, Cavalcante SC, Cohn S, Pacheco AG, Moulton LH, et al. Survival of HIV patients with tuberculosis started on simultaneous or deferred HAART in the THRio cohort, Rio de Janeiro, Brazil. Braz J Infect Dis 2014; 18(5): 491-5. http://doi.org/10.1016/j.bjid.2014.02.004
    » https://doi.org/http://doi.org/10.1016/j.bjid.2014.02.004
  • 21
    Durovni B, Saraceni V, Moulton LH, Pacheco AG, Cavalcante SC, King BS, et al. Effect of improved tuberculosis screening and isoniazid preventive therapy on incidence of tuberculosis and death in patients with HIV in clinics in Rio de Janeiro, Brazil: a stepped wedge, cluster-randomised trial. Lancet Infect Dis 2013; 13(10): 852-8. http://doi.org/10.1016/S1473-3099(13)70187-7
    » https://doi.org/http://doi.org/10.1016/S1473-3099(13)70187-7
  • 22
    Silva Escada RO, Velasque L, Ribeiro SR, Cardoso SW, Marins LMS, Grinsztejn E, et al. Mortality in patients with HIV-1 and tuberculosis co-infection in Rio de Janeiro, Brazil - associated factors and causes of death. BMC Infect Dis 2017; 17: 373. http://doi.org/10.1186/s12879-017-2473-y
    » https://doi.org/http://doi.org/10.1186/s12879-017-2473-y
  • 23
    Martin DA, Luz PM, Lake JE, Clark JL, Veloso VG, Moreira RI, et al. Improved virologic outcomes over time for HIV-infected patients on antiretroviral therapy in a cohort from Rio de Janeiro, 1997-2011. BMC Infect Dis 2014; 14: 322. http://doi.org/10.1186/1471-2334-14-322
    » https://doi.org/http://doi.org/10.1186/1471-2334-14-322
  • 24
    Moreira RI, Luz PM, Struchiner CJ, Morgado M, Veloso VG, Keruly JC, et al. Immune Status at Presentation for HIV Clinical Care in Rio de Janeiro and Baltimore. J Acquir Immune Defic Syndr 2011; 57: S171-8. http://doi.org/10.1097/QAI.0b013e31821e9d59
    » https://doi.org/http://doi.org/10.1097/QAI.0b013e31821e9d59
  • 25
    Souza Jr. PR, Szwarcwald CL, Castilho EA. Delay in introducing antiretroviral therapy in patients infected by HIV in Brazil, 2003-2006. Clinics 2007; 62(5): 579-84. http://doi.org/10.1590/S1807-59322007000500008
    » https://doi.org/http://doi.org/10.1590/S1807-59322007000500008
  • 26
    Zambenedetti G, Silva RAN da. Descentralização da atenção em HIV-Aids para a atenção básica: tensões e potencialidades. Physis 2016; 26(3): 785-806. http://doi.org/10.1590/s0103-73312016000300005
    » https://doi.org/http://doi.org/10.1590/s0103-73312016000300005
  • 27
    Saraceni V, Cruz MM da, Lauria L de M, Durovni B. Trends and characteristics of AIDS mortality in the Rio de Janeiro city after the introduction of highly active antiretroviral therapy. Braz J Infect Dis 2005; 9(3): 209-15. http://doi.org/10.1590/S1413-86702005000300003
    » https://doi.org/http://doi.org/10.1590/S1413-86702005000300003
  • 28
    Cunha CC, Teixeira R, França E. Avaliação da investigação de óbitos por causas mal definidas no Brasil em 2010. Epidemiol Serv Saúde 2017; 26(1): 19-30. http://doi.org/10.5123/S1679-49742017000100003
    » https://doi.org/http://doi.org/10.5123/S1679-49742017000100003
  • 29
    Pacheco AG, Saraceni V, Tuboi SH, Lauria LM, Moulton LH, Faulhaber JC, et al. Estimating the extent of underreporting of mortality among HIV-infected individuals in Rio de Janeiro, Brazil. AIDS Res Hum Retroviruses 2011; 27(1): 25-8. http://doi.org/10.1089/aid.2010.0089
    » https://doi.org/http://doi.org/10.1089/aid.2010.0089

  • Financial support: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa de Apoio à Pesquisa Estratégica em Saúde (Papes).

Publication Dates

  • Publication in this collection
    20 Mar 2020
  • Date of issue
    2020

History

  • Received
    20 Apr 2018
  • Reviewed
    05 Nov 2018
  • Accepted
    08 Jan 2019
Associação Brasileira de Pós -Graduação em Saúde Coletiva São Paulo - SP - Brazil
E-mail: revbrepi@usp.br