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Is early HIV infection diagnosis at a reference center a reality in the state of Ceara?

Abstract

INTRODUCTION:

Early diagnosis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) can decrease transmission and significantly affect morbidity and mortality; however, Brazil still confronts the reality of late HIV diagnosis.

METHODS:

Medical records of 284 HIV-positive patients were reviewed in this cross-sectional study.

RESULTS:

Of all patients, 28% were diagnosed in the context of health assessments, whereas 27% were symptomatic at diagnosis. Early HIV infection (Group 1) was diagnosed in 60.2% of participants. They were younger than those with late diagnosis (Group 2) (p = 0.002).

CONCLUSIONS:

These findings highlight the need for strategies to increase HIV testing in asymptomatic individuals and older patients.

Keywords:
Acquired immunodeficiency syndrome; HIV; Early diagnosis; STI

Acquired immunodeficiency syndrome (AIDS) is a major public health issue. From the beginning of the AIDS epidemic until June 2015, 798,366 cases were diagnosed in Brazil, of which 17,933 were diagnosed in the State of Ceara. In the last five years, about 40,600 new cases have been diagnosed annually in Brazil11. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Boletim Epidemiológico - Aids e DST. Brasília: MS; 2016. Atualizado em 25 de agosto de 2017; citado em 30 de novembro de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016 .
http://www.aids.gov.br/pt-br/pub/2016/bo...
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The Ministry of Health estimated that by the end of 2014, there were 781,000 people living with HIV/AIDS (PLWHA) in Brazil, of whom only 83% had been diagnosed, 66% were regularly undergoing follow-up at health centers, 52% had started antiretroviral therapy (ART), and 46% had undetectable viral loads (VL) after six months of treatment11. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Boletim Epidemiológico - Aids e DST. Brasília: MS; 2016. Atualizado em 25 de agosto de 2017; citado em 30 de novembro de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016 .
http://www.aids.gov.br/pt-br/pub/2016/bo...
. These numbers have not yet reached the targets established by the Joint United Nations Programme on HIV/AIDS in the 2014 Paris Declaration, where several countries committed to actions to achieve the 90-90-90 targets by 2020; that is, 90% of PLWHA will know their HIV status, 90% of people with diagnosed HIV infection will receive sustained ART, and 90% receiving ART will have viral suppression22. Joint United Nations Programme on HIV/AIDS (UNAIDS). 90-90-90 An ambitious treatment target to help end the AIDS epidemic. Geneva: UNAIDS; 2014. Updated 2017 August 25; cited 2017 Jan 1. Available from: Available from: http://www.unaids.org/en/resources/documents/2017/90-90-90 .
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.

In this regard, it is important to consider at what stage the patient is diagnosed, because patients in the acute phase, in which many individuals do not associate the symptoms with the disease despite a high viremia, are responsible for most instances of transmission33. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Manual Técnico para o Diagnóstico da Infecção pelo HIV. Brasília: 2013. Atualizado em 25 de agosto de 2017; citado em 1 de agosto de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/node/5778 .
http://www.aids.gov.br/pt-br/node/5778...
. There are still cases of patients who, even after diagnosis, do not take their treatment properly. Thus, effective strategies need to be created to improve diagnosis and initiation of treatment immediately because early diagnosis reduces HIV transmission since early follow-up and initiation of ART enable viral suppression44. Valentini MB, Toledo ML, Fonseca MO, Thiersch LM, Toledo IS, Machado FC, et al. Evaluation of late presentation for HIV treatment in a reference center in Belo Horizonte, Southeastern Brazil, from 2008 to 2010. Infect Dis. 2015;19(3):253-62..

Many individuals are still diagnosed late in Brazil, especially men and elderly individuals. Although the national laboratory diagnosis rate of late-stage HIV infection CD4 T-helper lymphocytes (CD4TL) <200 cells/dL decreased from 31% in 2009 to 25% in 2015, there are regional differences, with the highest rates occurring mainly in the North and Northeast regions. Between 2010 and 2014, the mean initial CD4TL counts of patients diagnosed in the State of Ceará and its capital, Fortaleza, were 287 and 286 cells/dL, respectively11. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Boletim Epidemiológico - Aids e DST. Brasília: MS; 2016. Atualizado em 25 de agosto de 2017; citado em 30 de novembro de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016 .
http://www.aids.gov.br/pt-br/pub/2016/bo...
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Therefore, it is important that specialized health care centers determine their rates of early detection and take actions to identify seropositive asymptomatic individuals in order to commence ART early and achieve viral suppression33. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Manual Técnico para o Diagnóstico da Infecção pelo HIV. Brasília: 2013. Atualizado em 25 de agosto de 2017; citado em 1 de agosto de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/node/5778 .
http://www.aids.gov.br/pt-br/node/5778...
. Consequently, these facilities could significantly contribute to reduced HIV transmission and improved quality of life of infected individuals.

Thus, this study evaluated the early detection rates of HIV infection in Fortaleza on the basis of epidemiological, social, and clinical data possibly related to diagnosis, provided by a specialized HIV/AIDS care center in the city.

Medical records of 284 HIV-positive patients followed up at the Specialized Care Service of the Integrated Medical Care Center, University of Fortaleza (SAE NAMI/UNIFOR) from 2010 to 2014 were reviewed in this observational, cross-sectional study.

Patients aged >18 years and actively undergoing outpatient follow-up were included in the study. Patients were selected at random according to the availability of medical records. Epidemiological, clinical, and laboratory data were collected from patient medical records. Patients were classified into two groups on the basis of early (CD4TL count ≥ 350 cells/dL) or late (CD4TL count < 350 cells/dL) diagnosis.

Most patients were male (237; 83.4%) with a mean age of 33.7 (± 10.5) years. Although SAE NAMI/UNIFOR is a reference center for the treatment of patients in Fortaleza, 27 patients (9.5%) were from neighboring cities. The educational background of the 146 participants (51.4%) was good (at least a high school diploma). The median time between diagnosis and commencement of follow-up was two months (range: 0-60 months). The median CD4TL count at the commencement of follow-up was 399 cells/dL (range: 11-1,714), corresponding to 189 and 567 cells/dL in the late and early diagnosis groups, respectively.

Although 171 (60.2%) patients were diagnosed with early HIV infection, 76 (27%) patients had requested testing because of symptoms related to HIV infection. Their median CD4TL count was 265 cells/dL (range: 15-1,305). A history of sexually transmitted infections (STIs) was present in 138 (48.6%) patients. However, previous STIs were the reason for anti-HIV serology tests in only 18 patients (6%). Other frequent reasons for testing included a serum-positive partner by 39 (14%) patients and blood donation by 15 (5%) patients. In addition, 80 (28%) patients were diagnosed with HIV infection when tested upon their own request (Figure 1).

FIGURE 1:
Reasons for anti-HIV serological testing among HIV-positive patients undergoing follow-up at the HIV/AIDS Specialized Care Service of the Integrated Medical Care Center, Fortaleza/CE, 2010-2014. STI: sexually transmitted infection; HIV: human immunodeficiency virus; AIDS: acquired immunodeficiency syndrome

In the analysis of epidemiological variables, only age showed a significant difference between groups (early vs. late diagnosis) with the early diagnosis group being younger than the late diagnosis group (p = 0.002). The analysis of prevalence according to risk factors showed no significant differences (Table 1).

TABLE 1:
Analysis of epidemiological variables related to early or late diagnosis among HIV-positive patients undergoing follow-up at the HIV/AIDS Specialized Care Service of the Integrated Medical Care Center, Fortaleza/CE, 2010-2014.

Most subjects (60.2%) undergoing follow-up at the health care service were diagnosed early, with CD4TL counts ≥ 350 cells/dL and a median cell count of 399 cells/dL. These data are concordant with previously reported domestic data, indicating an increase in early diagnosis in recent years. In 2009, 51% of patients diagnosed in Brazil had CD4TL counts > 350 cells/dL. This percentage increased to 58% in 2015, probably because of mass screening aimed at testing asymptomatic patients. However, the tests covered mainly the female population because screening is mandatory for prenatal care. Thus, late diagnosis is more common among men11. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Boletim Epidemiológico - Aids e DST. Brasília: MS; 2016. Atualizado em 25 de agosto de 2017; citado em 30 de novembro de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016 .
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. This study could not identify a statistically significant difference with regard to patient sex when comparing the two groups. International data also show a tendency toward earlier diagnosis of HIV infection. According to data from the Centers for Disease Control and Prevention (CDC) in the United States, 25.4% of patients older than 13 years of age had progressed to stage 3 HIV infection (AIDS) at diagnosis in 2009. This prevalence decreased to 23.6% in 201355. Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data - United States and 6 dependent areas - 2013. HIV AIDS Surveill Rep. 2015;20(2):1-70..

Analysis of the reasons that led to the diagnosis of HIV infection revealed that most patients (28%) were asymptomatic and were screened voluntarily, whereas 27% of the patients had symptoms related to HIV infection, which led to their diagnosis. The latter had a low median CD4TL count (265 cells/dL). Studies have shown that symptomatic individuals diagnosed with so-called B symptoms according to the 1993 CDC classification criteria66. Centers for Disease Control and Prevention. 1993 revised classification system for hiv infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):1-19. (including oral candidiasis, herpes zoster, and constitutional symptoms, among others) may have been diagnosed late and might have a significant risk of developing AIDS within 6 months and higher 12-month mortality rates77. Lodwick RK, Nakagawa F, Sighem A, Sabin CA, Phillips AN. Use of surveillance data on hiv diagnoses with hiv-related symptoms to estimate the number of people living with undiagnosed HIV in need of antiretroviral therapy. PLoS One. 2015;10(3):1-9.. Thus, the treatment for symptomatic individuals with B or C symptoms is critical to avoiding rapid disease progression. Nearly one-third of the patients in this study were diagnosed with a poorer immune response and therefore presented a higher risk of developing AIDS or more severe complications. The seropositive population, even when asymptomatic, should initiate ART as soon as possible as it is an important measure for reducing harm and improving the quality of life. Early diagnosis, together with early ART initiation, may contribute to reduced transmission, as asymptomatic seropositive individuals who are unaware of their serological status may continue the same risky behaviors that led to their infection88. Lima VD, Reuter A, Harrigan PR, Lourenço L, Chau W, Hull M, et al. Initiation of antiretroviral therapy at high CD4+ cell counts is associated with positive treatment outcomes. AIDS. 2015;29(14):1871-82..

Even though significant data were missing, the analysis of sexual partnerships showed that 37.3% of patients reported having many partners. In addition, 23.2% reported having had sex with a partner known to be HIV-positive. These findings, coupled with the fact that statistics on drug use were low, suggest that sexual exposure must have been the primary form of HIV transmission. These findings are concordant with domestic and international data, which suggest that sexual intercourse is the most significant form of HIV transmission in both men and women. Another important factor is multiple sexual partners, especially casual partners99. The Joint United Nations Programme on HIV/AIDS (UNAIDS ). Prevention Gap Reportion. Geneva: UNAIDS ; 2016. Updated 2017 August 25; cited 2016 Jul 11. Available from: Available from: http://www.unaids.org/en/resources/documents/ 2016/prevention-gap .
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. Over the years, a decline has been observed in the percentage of exposure to injection drug use in Brazil11. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Boletim Epidemiológico - Aids e DST. Brasília: MS; 2016. Atualizado em 25 de agosto de 2017; citado em 30 de novembro de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016 .
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This study showed a prevalence of younger people in the group with an early diagnosis. Data from the 2015 Epidemiological Bulletin reported a similar finding, showing that elderly people tend to be diagnosed later11. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Boletim Epidemiológico - Aids e DST. Brasília: MS; 2016. Atualizado em 25 de agosto de 2017; citado em 30 de novembro de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016 .
http://www.aids.gov.br/pt-br/pub/2016/bo...
. CDC data from 2013 also showed the prevalence of symptomatic patients among groups of elderly people. According to these data, the prevalence of patients diagnosed with stage 3 HIV infection (CD4TL counts < 200 cells/dL) was 23.6% in the United States. Among these cases, most were heterosexual men older than 55 years66. Centers for Disease Control and Prevention. 1993 revised classification system for hiv infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):1-19..

Several studies have highlighted the fact that older people have been diagnosed with lower levels of CD4TL. This is because the infection progresses more rapidly in this age group because of immunosenescence and the presence of multiple comorbidities and because these individuals are tested less often than younger people1010. Asher I, Guri KM, Elbirt D, Bezalel SR, Maldarelli F, Mor O, et al. Characteristics and outcome of patients diagnosed with HIV at older age. Medicine. 2016;95(1):1-8.. Stigma, refusal to test, and misperception of patients and professionals about risks are barriers to early diagnosis in this age group. Even in places with a high prevalence of HIV infection, where the CDC recommends screening of all sexually active people and injection drug users, elderly individuals often postpone testing, mainly because of the lack of perception of risk behaviors in their population. These misconceptions prevent the diagnosis in individuals in whom the infection rapidly progresses to AIDS, leading to increased mortality in the short term1111. Ford CL, Lee SJ, Wallace SP, Nakazono T, Newman PA, Cunningham WE. HIV testing among clients in high HIV prevalence venues: disparities between older and younger adults. J Int Assoc Provid AIDS Care . 2015;27(2):189-97..

Although 48.6% of the patients in this study reported previous STIs, no difference in STI prevalence was found between the groups (p = 0.79). Only 6% of the patients reported a current STI as the reason for requesting the anti-HIV serological test. STIs are known risk factors for HIV infection, which are also included in this group because of shared transmission routes. Individuals with non-ulcerative STIs have a 3- to 10-fold increased risk of becoming infected with HIV, whereas those with ulcers in the genital tract have an 18-fold increased risk1212. Szwarcwald CL, Andrade CLT, Pascom ARP, Fazito E, Pereira GFM, Penha IT. HIV-related risky practices among Brazilian young men. Cad Saúde Pública. 2011;27(Sup1):519-26.. Thus, as risk behaviors are shared between STIs and HIV infection, HIV testing is recommended whenever a patient is diagnosed with an STI, either currently or previously, for early diagnosis and breaking the chain of transmission1313. Ministério da Saúde (MS). Secretaria de Vigilância em Saúde- Departamento de DST, AIDS e Hepatites Virais. Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis. Brasília: 2015. Atualizado em 25 de agosto de 2017; citado em 16 de junho de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes .
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. Therefore, the findings of this study indicate a failure in the indications for screening tests, which should be performed when patients with a history of STIs are identified, regardless if the history is previous or current.

In this study, about 5% of patients were diagnosed when they volunteered to donate blood. Unfortunately, this is a common finding in other studies. One of the reasons is that some individuals seek to donate blood to undergo anti-HIV serological screening as they view themselves to be at risk for this infection. Although altruism is the primary motivation among blood donors, many seek this strategy to also be tested free of charge and without further counseling1414. Goncalez TT, Blatyta PF, Santos FM, Montebello S, Esposti SPD, Hangai FN, et al. Does offering HIV testing at the time of blood donation reduce transfusion-transmission risk and increase disclosure counseling? Results of a randomized controlled trial, São Paulo, Brazil. Transfusion. 2015;55(6):1214-22.. In addition, some donors omit information about their risk behaviors in specific questionnaires, which is a reason for concern1515. Goncalez TT, Sabino EC, Salles NA, Almeida-Neto C, Mendrone-Jr A, Dorlhiac-Laccer PE, et al. The impact of simple donor education on donor behavioral deferral and infectious disease rates in São Paulo, Brazil. Transfusion. 2010;50(4):909-17.. These findings reinforce the hypothesis that, although less prevalent, the transfusion route of HIV transmission should be a constant concern and that measures to identify HIV-positive donors should be further improved.

The findings of this study may be limited because the sample included only patients from a single SAE, which limits the extrapolation of the results to the general population of those recently diagnosed with HIV.

The results of this study showed that although most patients were diagnosed with a reasonable immunological status (median CD4TL 399 cells/dL) more than a quarter of them were diagnosed with symptoms related to HIV infection. The results also showed an increased prevalence of elderly patients in the late diagnosis group. Finally, although almost half of the patients reported the occurrence of STIs, in only 6% was it the reason for requesting anti-HIV serological tests.

These findings suggest that both SAEs and competent authorities should engage in the global fight against HIV more fully, including developing strategies to encourage the population to undergo testing in order to identify individuals with HIV infection in its asymptomatic phase, with a particular focus on individuals who are sexually at-risk and on elderly people. This is the only approach in which we will be able to participate in the global fight against the AIDS epidemic, the efforts of which are ultimately focused on the early diagnosis of HIV infection so that ART may be initiated in at least 90% of HIV-positive patients.

Ethical considerations

The study was approved by the Institutional Review Board of the University of Fortaleza (Opinion no. 355.510).

Acknowledgments

We thank all the people who supported this research, particularly the patients involved in the study.

REFERENCES

  • 1
    Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Boletim Epidemiológico - Aids e DST. Brasília: MS; 2016. Atualizado em 25 de agosto de 2017; citado em 30 de novembro de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016
    » http://www.aids.gov.br/pt-br/pub/2016/boletim-epidemiologico-de-aids-2016
  • 2
    Joint United Nations Programme on HIV/AIDS (UNAIDS). 90-90-90 An ambitious treatment target to help end the AIDS epidemic. Geneva: UNAIDS; 2014. Updated 2017 August 25; cited 2017 Jan 1. Available from: Available from: http://www.unaids.org/en/resources/documents/2017/90-90-90
    » http://www.unaids.org/en/resources/documents/2017/90-90-90
  • 3
    Ministério da Saúde (MS). Secretaria de Vigilância em Saúde. Departamento de DST, AIDS e Hepatites Virais. Manual Técnico para o Diagnóstico da Infecção pelo HIV. Brasília: 2013. Atualizado em 25 de agosto de 2017; citado em 1 de agosto de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/node/5778
    » http://www.aids.gov.br/pt-br/node/5778
  • 4
    Valentini MB, Toledo ML, Fonseca MO, Thiersch LM, Toledo IS, Machado FC, et al. Evaluation of late presentation for HIV treatment in a reference center in Belo Horizonte, Southeastern Brazil, from 2008 to 2010. Infect Dis. 2015;19(3):253-62.
  • 5
    Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data - United States and 6 dependent areas - 2013. HIV AIDS Surveill Rep. 2015;20(2):1-70.
  • 6
    Centers for Disease Control and Prevention. 1993 revised classification system for hiv infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):1-19.
  • 7
    Lodwick RK, Nakagawa F, Sighem A, Sabin CA, Phillips AN. Use of surveillance data on hiv diagnoses with hiv-related symptoms to estimate the number of people living with undiagnosed HIV in need of antiretroviral therapy. PLoS One. 2015;10(3):1-9.
  • 8
    Lima VD, Reuter A, Harrigan PR, Lourenço L, Chau W, Hull M, et al. Initiation of antiretroviral therapy at high CD4+ cell counts is associated with positive treatment outcomes. AIDS. 2015;29(14):1871-82.
  • 9
    The Joint United Nations Programme on HIV/AIDS (UNAIDS ). Prevention Gap Reportion. Geneva: UNAIDS ; 2016. Updated 2017 August 25; cited 2016 Jul 11. Available from: Available from: http://www.unaids.org/en/resources/documents/ 2016/prevention-gap
    » http://www.unaids.org/en/resources/documents/ 2016/prevention-gap
  • 10
    Asher I, Guri KM, Elbirt D, Bezalel SR, Maldarelli F, Mor O, et al. Characteristics and outcome of patients diagnosed with HIV at older age. Medicine. 2016;95(1):1-8.
  • 11
    Ford CL, Lee SJ, Wallace SP, Nakazono T, Newman PA, Cunningham WE. HIV testing among clients in high HIV prevalence venues: disparities between older and younger adults. J Int Assoc Provid AIDS Care . 2015;27(2):189-97.
  • 12
    Szwarcwald CL, Andrade CLT, Pascom ARP, Fazito E, Pereira GFM, Penha IT. HIV-related risky practices among Brazilian young men. Cad Saúde Pública. 2011;27(Sup1):519-26.
  • 13
    Ministério da Saúde (MS). Secretaria de Vigilância em Saúde- Departamento de DST, AIDS e Hepatites Virais. Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis. Brasília: 2015. Atualizado em 25 de agosto de 2017; citado em 16 de junho de 2016. Disponível em: Disponível em: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes
    » http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes
  • 14
    Goncalez TT, Blatyta PF, Santos FM, Montebello S, Esposti SPD, Hangai FN, et al. Does offering HIV testing at the time of blood donation reduce transfusion-transmission risk and increase disclosure counseling? Results of a randomized controlled trial, São Paulo, Brazil. Transfusion. 2015;55(6):1214-22.
  • 15
    Goncalez TT, Sabino EC, Salles NA, Almeida-Neto C, Mendrone-Jr A, Dorlhiac-Laccer PE, et al. The impact of simple donor education on donor behavioral deferral and infectious disease rates in São Paulo, Brazil. Transfusion. 2010;50(4):909-17.
  • Financial support: The research received no institutional or private financing.

Publication Dates

  • Publication in this collection
    Jul-Aug 2018

History

  • Received
    03 Oct 2017
  • Accepted
    28 Dec 2017
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