Dayse Pereira Campos

Changing Mortality Profile among HIV-Infected Patients in Rio de Janeiro, Brazil: Shifting from AIDS to Non-AIDS Related Conditions in the HAART Era

Introduction We describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ). Methods Adult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients’ medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling. Results A total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7–9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986–1991 to 1.35/100PYs in 2007–2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause. Conclusions Our results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.

Early mortality and cause of deaths in patients using HAART in Brazil and the United States.

Objective:To compare the early mortality pattern and causes of death among patients starting HAART in Brazil and the United States. Methods:We analyzed the combined data from two clinical cohorts followed at the Johns Hopkins AIDS Service in Baltimore, United States, and the Evandro Chagas Clinical Research Institute AIDS Clinic in Rio de Janeiro, Brazil. Participants included those who entered either cohort between 1999 and 2007 and were antiretroviral naive. Follow-up was at 1 year since HAART initiation. Cox proportional hazards regression analysis was used to assess the role of the city on the risk of death. Results:A total of 859 and 915 participants from Baltimore and Rio de Janeiro, respectively, were included. In Rio de Janeiro, 64.7% of deaths occurred within 90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365 days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%) predominated as causes of death in Rio de Janeiro and Baltimore, respectively. Risk of death was similar in both cities (hazard ratio 1.04; P value = 0.95) after adjusting for CD4+ T cell count, age, sex, HIV risk group, prior AIDS-defining illness, and Pneumocystis jirovecii pneumonia and Mycobacterium avium prophylaxis. Individuals with CD4+ T cell count less than or equal to 50 cells/μl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P = 0.03) were more likely to die. Conclusion:Although late HIV diagnosis is a problem both in developed and developing countries, differences in the timing and causes of deaths clearly indicate that, besides interventions for early HIV diagnosis, different strategies to curb early mortality need to be tailored in each country.

Análise de sobrevivência: teoria e aplicações em saúde

O objetivo apoiar o desenvolvimento metodologico em analise de dados longitudinais, atraves da aplicacao, teste e disseminacao de metodos estatisticos inovadores no contexto da saude, particularmente os voltados para a analise de sobrevida

Is pregnancy associated with severe dengue? A review of data from the Rio de Janeiro surveillance information system.

Background Dengue is a reportable disease in Brazil; however, pregnancy has been included in the application form of the Brazilian notification information system only after 2006. To estimate the severity of maternal dengue infection, the available data that were compiled from January 2007 to December 2008 by the official surveillance information system of the city of Rio de Janeiro were reviewed. Methods and Principal Findings During the study period, 151,604 cases of suspected dengue infection were reported. Five hundred sixty-one women in their reproductive age (15–49 years) presented with dengue infection; 99 (18.1%) pregnant and 447 (81.9%) non-pregnant women were analyzed. Dengue cases were categorized using the 1997 WHO classification system, and DHF/DSS were considered severe disease. The Mann-Whitney test was used to compare maternal age, according to gestational period, and severity of disease. A chi-square test was utilized to evaluate the differences in the proportion of dengue severity between pregnant and non-pregnant women. Univariate analysis was performed to compare outcome variables (severe dengue and non-severe dengue) and explanatory variables (pregnancy, gestational age and trimester) using the Wald test. A multivariate analysis was performed to assess the independence of statistically significant variables in the univariate analysis. A p-value<0.05 was considered statistically significant. A higher percentage of severe dengue infection among pregnant women was found, p = 0.0001. Final analysis demonstrated that pregnant women are 3.4 times more prone to developing severe dengue (OR: 3.38; CI: 2.10–5.42). Mortality among pregnant women was superior to non-pregnant women. Conclusion Pregnant women have an increased risk of developing severe dengue infection and dying of dengue.

Survival of AIDS patients using two case definitions, Rio de Janeiro, Brazil, 1986-2003

Background:Recent studies have shown substantial increases in the survival of AIDS patients in developed countries and in Brazil as a result of antiretroviral therapy (ART) and prophylaxis for opportunistic infections. This study compares survival rates using the Brazilian Ministry of Health 2004 and Centers for Disease Control and Prevention (CDC) 1993 case definitions in a large HIV/AIDS referral centre in Rio de Janeiro. Methods:Survival after AIDS diagnosis was assessed in a clinic-based cohort of 1415 individuals using the Kaplan–Meier method and Cox proportional hazards models. Results:There were 393 (88%) deaths from AIDS-related causes and 52 (12%) from unrelated or unknown causes. A total of 205 patients (14%) were lost to follow-up and 765 patients (55%) remained alive until the end of the study. Three-quarters of patients (75%) were still alive 22 months [95% confidence interval (CI) 19–26] after the AIDS diagnosis according to the CDC case definition and 31 months (95% CI 26–36) according to the Ministry of Health case definition. Independent predictors of survival included AIDS defined by CD4 cell count and any use of highly active antiretroviral therapy, with either case definition, and initial stage of the case, with the Ministry of Health case definition. Conclusion:Survival observed in this reference centre is comparable or longer than other international studies, although the choice of case definition criterion influenced findings. Adoption of the Ministry of Health case definition may enhance the ability to track the use of and outcomes from ART among AIDS patients.

Sporotrichosis: an emerging neglected opportunistic infection in HIV-infected patients in Rio de Janeiro, Brazil.

Sporotrichosis associated with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil, affecting a large at-risk population, which includes HIV-infected individuals. We assessed patients co-infected by Sporothrix spp. and HIV over time in the context of an unabated sporotrichosis epidemic. A retrospective cohort retrieved information from a National reference institute for infectious diseases regarding 48 patients with sporotrichosis-HIV co-infection (group 1) as well as 3,570 patients with sporotrichosis (group 2), from 1987 through March 2013. Most patients from group 1 were male (68.8%), whereas women were predominant in group 2 (69.1%; p<0.0001). Patients from group 1 were younger than those from group 2 (μ = 38.38±10.17 vs. 46.34±15.85; p<0.001) and differed from group 2 in terms of their race/ethnic background, with 70.8% non-white patients in group 1 vs. 38.6% from group 2 (p<0.0001). Close to half (∼44%) of the patients from group 1 were hospitalized due to sporotrichosis over time, whereas hospitalization was very unlikely in group 2, among whom approximately 1% were hospitalized over time. Dissemination of sporotrichosis was the main cause of hospitalization in both groups, although it was more common among hospitalized patients from group 1 (19/21 [90.5%] vs. 16/37 [43.2%]; p<0.001). Over the period under analysis, eight patients died due to sporotrichosis (3/48 vs. 5/3,570). The diagnosis of sporotrichosis elicited HIV testing and subsequent diagnosis in 19/48 patients, whereas 23/48 patients were simultaneously diagnosed with the two infections. HIV infection aggravates sporotrichosis, with a higher incidence of severe disseminated cases and a higher number of hospitalizations and deaths. Underserved populations, among whom sporotrichosis has been propagated, have been affected by different transmissible (e.g., HIV) and non-transmissible diseases. These populations should be targeted by community development programs and entitled to integrated management and care of their superimposed burdens.

Comparison of clinical response to initial highly active antiretroviral therapy in the patients in clinical care in the United States and Brazil

Background:US and Brazilian studies indicate that highly active antiretroviral therapy (HAART) has been effective in reducing morbidity and mortality from HIV/AIDS. Differences exist in the adoption and patterns of antiretroviral drug use and in the incidence of AIDS-defining illness (ADI) between the 2 countries, however, and there has not been a direct comparison of clinical response between Brazil and the United States. We sought to determine if there have been differences in the clinical response to HAART from HIV clinical practices in the United States and Brazil. Methods:We compared 2 similarly designed clinical cohorts from Baltimore, Maryland and Rio de Janeiro, Brazil. Patients who started HAART from 1997 to 2004 were compared for HIV-1 RNA suppression and CD4+ T-lymphocyte count change by 1 year of therapy and for development of an ADI up to 6 years of follow-up. A total of 1368 patients from Baltimore and 1045 patients from Rio de Janeiro were studied. Results:There was no difference by location in achieving an HIV-1 RNA level <400 copies/mL (46.9% in Rio de Janeiro, 50.8% in Baltimore), in the log change in HIV-1 RNA level (−1.65 log in Rio de Janeiro, −1.63 log in Baltimore), or in the change in CD4 count (116 cells/mm3 in Rio de Janeiro, 122 cells/mm3 in Baltimore) by 12 months after starting HAART. By Kaplan-Meier analysis and Cox regression adjusted for demographic and clinical prognostic factors, there was no difference by location in development of the first ADI after starting HAART (relative hazard = 1.02; 95% confidence interval: 0.82 to 1.25 for Rio de Janeiro vs. Baltimore). The most commonly occurring ADI in Rio de Janeiro was tuberculosis (27.7% of patients), and the most commonly occurring ADI in Baltimore was esophageal candidiasis (36.8% of patients). Conclusions:There were only minor differences in clinical response to the use of HAART comparing Rio de Janeiro with Baltimore, despite differences in patterns of antiretroviral drug use and ADI incidence. This analysis indicates that HAART can be similarly effective in treating HIV/AIDS in countries with different economies.

Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil.

BackgroundMalaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. Clinically, the progression of the disease can be life-threatening if it is not promptly diagnosed and properly treated. Through treatment, the radical cure of Plasmodium vivax infection can be achieved, thus preventing potential relapses and the emergence of new cases outside the Amazon region in Brazil. Surveillance for therapeutic failure in non-endemic areas is advantageous, as it is unlikely that recurrence of the disease can be attributed to a new malaria infection in these regions.MethodsAn observational study of 53 cases of P. vivax and mixed (P. vivax and Plasmodium falciparum) malaria was conducted at a travel medicine centre between 2005 and 2011 in Rio de Janeiro and a descriptive analysis of the potential factors related to recurrence of P. vivax malaria was performed. Groups with different therapeutic responses were compared using survival analysis based on the length of time to recurrence and a set of independent variables thought to be associated with recurrence.ResultsTwenty-one relapses (39.6%) of P. vivax malaria were observed. The overall median time to relapse, obtained by the Kaplan-Meier method, was 108 days, and the survival analysis demonstrated an association between non-weight-adjusted primaquine dosing and the occurrence of relapse (p < 0.03). Primaquine total dose at 3.6 mg/kg gave improved results in preventing relapses.ConclusionsA known challenge to individual cure and environmental control of malaria is the possibility of an inappropriate, non-weight-based primaquine dosing, which should be considered a potential cause of P. vivax malaria relapse. Indeed, the total dose of primaquine associated with non-occurrence of relapses was higher than recommended by Brazilian guidelines.

Trends in AIDS-defining opportunistic illnesses incidence over 25 years in Rio de Janeiro, Brazil.

Objectives To assess the temporal trends in incidence of AIDS-defining opportunistic illnesses in an urban cohort of a middle-income country. Methods HIV infected patients aged ≥18 years at cohort entry were included in this analysis. We calculated incidence rates per 1000 persons-years of observation for the first opportunistic illness presented after cohort enrollment, from 1987 to 2012. Trends for overall and specific opportunistic illnesses were tested and incidence rate ratios for the most recent calendar period were calculated as the ratio between the incidence rate observed in the most recent period of the study (2009–2012) and the incidence rate observed in first period of the study (1987–1990). Results Overall, 3378 patients were included in this analysis; of which 1119 (33%) patients presented an opportunistic illness during follow up. Incidence rates of all opportunistic illnesses decreased over time, and the overall opportunistic illness incidence rates fell from 295.4/1000 persons-years in 1987–1990 to 34.6/1000 persons-years in 2009–2012. Tuberculosis, esophageal candidiasis, cerebral toxoplasmosis and Pneumocystis jirovecii pneumonia were the most incident opportunistic illnesses in the cohort. Tuberculosis had the highest incidence rate in the study period. The peak in tuberculosis incidence occurred in 1991–1993 (80.8/1000 persons-years). Cerebral toxoplasmosis was the third most incident opportunistic illness in the study, with a peak of incidence of 43.6/1000 persons-year in 1987–1990. Conclusions All opportunistic illnesses incidence rates decreased over the years but they still occur in an unacceptable frequency. Tuberculosis co-infection among HIV-infected persists as an important challenge for health care professionals and policy makers in our setting. Impressively high rates of cerebral toxoplasmosis were found suggesting that its incidence among HIV-infected is linked to the high prevalence of Toxoplasma gondii infection in the general population.

Effect of sociodemographic, clinical-prophylactic and therapeutic procedures on survival of AIDS patients assisted in a Brazilian outpatient clinic

The Brazilian AIDS Program offers free and universal access to antiretroviral therapy. This study investigates the influence of sociodemographic, clinical-prophylactic and therapeutic factors on survival, after AIDS diagnosis, in an open cohort of 1,420 patients assisted in a university hospital in the city of Rio de Janeiro (1995 _ 2002). Kaplan-Meier and Cox proportional hazards models were used to estimate the effect of variables in the three dimensions studied. The overall survival time of the upper quartile was 24 months (CI95%= 20.5-27.5), increasing from 14 months, in 1995, to 46 months, in 1998. We found a protective effect of heterosexual behavior against death that could be attributed to the increasing female-to-male sex ratio in the cohort, which coincided with the time of therapy introduction. Low schooling, hospital admission and lack of follow-up were identified as risk factors for death; PCP and Toxoplasmosis prophylaxis were protective. The number of attempts required to consolidate the antiretroviral therapy showed no significant effect on survival. The full model, which includes the number of antiretroviral drugs in the regimen, confirmed the triple therapy as the best regimen. This study brings important information for designing guidelines to deal with different aspects related to the practical management of patients and their behavior, thus contributing to the success of the program of free access to antiretroviral therapy implemented in Brazil.