[Show abstract][Hide abstract] ABSTRACT: Previous cohort studies have demonstrated the beneficial effects of antiretroviral therapy (ART) on viral load suppression. We aimed to examine the factors associated with virologic suppression for HIV-infected patients on ART receiving care at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil.
[Show abstract][Hide abstract] ABSTRACT: In high-income settings, the spectrum of morbidity and mortality experienced by Human Immunodeficiency Virus (HIV)-infected individuals receiving combination antiretroviral therapy (cART) has switched from predominantly AIDS-related to non-AIDS-related conditions. In the context of universal access to care, we evaluated whether that shift would apply in Brazil, a middle-income country with universal access to treatment, as compared to France.
[Show abstract][Hide abstract] ABSTRACT: Reliable information on severe morbidity is essential for identifying priorities for case management and to guide resource allocation within the health sector.
This study describes overall, AIDS and non-AIDS related severe morbidity as well as mortality and its determinants in an urban cohort of HIV-infected individuals from a public health care institution, the Evandro Chagas Research Institute (IPEC) of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Severe morbid events were defined as all clinical diagnoses listed in hospitalization discharge records; all diagnoses were checked and validated. Generalized estimating equations models were used to estimate incidence rates while adjusting for within subject correlation.
Between 2000 and 2010, 3537 patients were followed for a total of 16960 person-years (PY) of follow-up. Over the years, annual incidence rate of severe morbid events, AIDS-related events, non-AIDS related events, and deaths significantly decreased from, respectively, 36.6, 12.9, 23.7, and 3.2 per 100PY in 2000 to 25.3, 7.9, 17.4, and 1.9 per 100PY in 2010. Patients' immunological profile significantly improved with time; 84% of the patients used antiretroviral therapy (cART) per year. Immunodeficiency was associated with a higher incidence rate of AIDS and non-AIDS related events as well as with the incidence rate of specific non-AIDS events (bacterial infections, toxicities, cardiovascular, renal and respiratory diseases).
Our results show that in a middle income country with access to cART, non-AIDS-related events represent an important cause of severe morbidity alongside a still high incidence rate of AIDS-related events.
[Show abstract][Hide abstract] ABSTRACT: To compare the effectiveness of first-line combination antiretroviral therapy (cART) between premenopausal and postmenopausal women.
ART-naïve women initiating cART between January 2000/June 2010 at the Instituto de Pesquisa Clínica Evandro Chagas Cohort were studied. Women were defined as postmenopausal after 12 consecutive months of amenorrhea. CD4 cell counts and HIV-1 RNA viral load (VL) measurements were compared between pre- and postmenopausal at 6, 12 and 24 months after cART initiation. Women who modified/discontinued a drug class or died due to an AIDS defining illness were classified as ART-failures. Variables were compared using Wilcoxon test, χ2 or Fisher's exact test. The odds of cART effectiveness (VL<400 copies/mL and/or no need to change cART) were compared using logistic regression. Linear model was used to access relationship between CD4 change and menopause.
Among 383 women, 328 (85%) were premenopausal and 55 (15%) postmenopausal. Median pre cART CD4 counts were 231 and 208 cells/mm(3) (p = 0.14) in pre- and postmenopausal women, respectively. No difference in the median pre cART VL was found (both 4.8 copies/mL). Median CD4 changes were similar at 6 and 12 months. At 24 months after cART initiation, CD4 changes among postmenopausal women were significantly lower among premenopausal women (p = 0.01). When the analysis was restricted to women with VL<400 copies/mL, no statistical difference was observed. Overall, 63.7% achieved cART effectiveness at 24 months without differences between groups at 6, 12 and 24 months.
Menopause status at the time of first-line cART initiation does not impact CD4 cell changes at 24 months among women with a virologic response. No relationship between menopause status and virologic response was observed.
PLoS ONE 01/2014; 9(2):e89299. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With the introduction of combined active antiretroviral therapy and the improved survival of HIV-infected patients, degenerative diseases and drug toxicity have emerged as long-term concerns. We studied the prevalence of decreased glomerular filtration rate (GFR) and associated risk factors in a cohort of HIV-infected patients from a middle-income country. Our cross-sectional study included all adult patients who attended an urban outpatient clinic in 2008. GFR was estimated using the CKD-EPI equation. The prevalence ratio (PR) of decreased GFR (defined as <60 mL/min/1.73 m2) was estimated using generalizing linear models assuming a Poisson distribution. We analyzed data from 1,970 patients, of which 82.9% had been exposed to ART. A total of 249 patients (12.6%) had a GFR between 60 and 89 mL/min/1.73 m2, 3.1% had a GFR between 30 and 59, 0.3% had a GFR between 15 and 29, and 0.4% had a GFR <15. Decreased GFR was found in only 74 patients (3.8%). In the multivariate regression model, the factors that were independently associated with a GFR below 60 mL/min/1.73 m2 were as follows: age ≥50 years (PR = 3.4; 95% CI: 1.7-6.8), diabetes (PR = 2.0; 95% CI: 1.2-3.4), hypertension (PR = 2.0; 95% CI: 1.3-3.2), current CD4+ cell count <350 cells/mm3 (PR = 2.1; 95% CI: 1.3-3.3), past exposure to tenofovir (PR = 4.7; 95% CI: 2.3-9.4) and past exposure to indinavir (PR = 1.7; 95% CI: 1.0-2.8). As in high-income countries, CKD was the predominant form of kidney involvement among HIV-infected individuals in our setting. The risk factors associated with decreased glomerular filtration were broad and included virus-related factors as well as degenerative and nephrotoxic factors. Despite the potential for nephrotoxicity associated with some antiretroviral drugs, in the short-term, advanced chronic renal disease remains very rare.
PLoS ONE 01/2014; 9(4):e93748. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a continuous debate on how to adequately evaluate long-term CD4+ cell count in response to combination antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected individuals. Our study evaluated the long-term CD4+ cell count response (up to ten years) after initiation of ART and described the differences in the CD4+ cell count response stratified by pretreatment CD4+ cell count, and other socio-demographic, behavioral, and clinical factors.
The study population included patients starting ART in the clinical cohorts of Rio de Janeiro, Brazil, and Baltimore, United States. Inverse probability of censoring weighting was used to estimate mean annual CD4+ cell counts while adjusting for choice of initial ART regimen, ART discontinuation and losses-to-follow-up.
From 1997 to 2011, 3116 individuals started ART; preferred initial regimen was NNRTI-based (63%). The median follow-up time was 5 years, 10% of the individuals had nine or more years of follow-up. Observed CD4+ cell counts increased throughout the ten years of follow-up. Weighted results, in contrast, increased up to year four and plateaued thereafter with 50% of the population reaching CD4+ cell counts of 449/μL or more. Out of all stratification variables considered, only individuals with pre-treatment CD4+ cell counts ≥350/μL showed increasing CD4+ cell counts over time with 76% surpassing the CD4+ cell count >500/μL threshold at year ten.
The present study corroborates the growing body of knowledge advocating early start of ART by showing that only patients who start ART early fully recover to normal CD4+ cell counts.
PLoS ONE 01/2014; 9(4):e93039. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: After antiretroviral therapy (ART) became available, there was a decline in the number of deaths in persons infected with HIV. Thereafter, there was a decrease in the proportion of deaths attributed to opportunistic infections and an increase in the proportion of deaths attributed to chronic comorbidities. Herein we extend previous observations from a nationwide survey on temporal trends in causes of death in HIV-infected patients in Brazil.
We describe temporal trends in causes of death among adults who had HIV/AIDS listed in the death certificate to those who did not. All death certificates issued in Brazil from 1999 to 2011 and listed in the national mortality database were included. Generalized linear mixed-effects logistic models were used to study temporal trends in proportions.
In the HIV-infected population, there was an annual adjusted average increase of 6.0%, 12.0%, 4.0% and 4.1% for cancer, external causes, cardiovascular diseases (CVD) and diabetes mellitus (DM), respectively, compared to 3.0%, 4.0%, 1.0% and 3.9%, in the non-HIV group. For tuberculosis (TB), there was an adjusted average increase of 0.3%/year and a decrease of 3.0%/year in the HIV and the non-HIV groups, respectively. Compared to 1999, the odds ratio (OR) for cancer, external causes, CVD, DM, or TB in the HIV group were, respectively, 2.31, 4.17, 1.76, 2.27 and 1.02, while for the non-HIV group, the corresponding OR were 1.31, 1.63, 1.14, 1.62 and 0.67. Interactions between year as a continuous or categorical variable and HIV were significant (p<0.001) for all conditions, except for DM when year was considered as a continuous variable (p = 0.76).
Non HIV-related co-morbidities continue to increase more rapidly as causes of death among HIV-infected individuals than in those without HIV infection, highlighting the need for targeting prevention measures and surveillance for chronic diseases among those patients.
PLoS ONE 01/2014; 9(4):e94636. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression.
AIDS Research and Therapy 01/2014; 11:29. · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The natural history of HIV infection has changed dramatically after the introduction of highly active antiretroviral therapy. Currently, opportunistic illnesses still represent a major cause of death and hospitalization in this population. In this study, we review the trends in opportunistic illnesses incidence rates and compare the results observed in high-income settings with that for low/middle income settings, with special attention given to studies from Brazil.
We systematically searched Pubmed, Web of Science, Lilacs and Google scholar for publications on HIV associated opportunistic illness. Studies reporting rates based on person-time for all opportunistic illnesses and/or the three opportunistic infections of interest, namely, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacterium avium complex were included.
Significant reductions in the incidence rates were demonstrated for opportunistic illnesses overall and also for the specific opportunistic infections included in the present study, both in high and low/middle income settings. Out of the 37 studies included in the present review, almost 70% were from high-income settings. All the studies conducted in low/middle income settings were single center studies and four were from Brazil. We found no study from Brazil reporting annual incidence rates of opportunistic illnesses.
Opportunistic illnesses remain an important public health problem. To better guide health policies in low/middle income settings (LMIS), multicenter cohort studies should be encouraged. Studies from Brazil are urgently needed to assess the current burden of opportunistic illnesses in our population and to support the planning of HIV/AIDS health care services organization.
The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 11/2013; · 1.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent Phase 2b dengue vaccine trials have demonstrated the safety of the vaccine and estimated the vaccine efficacy with further trials underway. In anticipation of vaccine roll-out, cost-effectiveness analysis of potential vaccination policies that quantify the dynamics of disease transmission are fundamental to the optimal allocation of available doses. We developed a dengue transmission and vaccination model and calculated, for a range of vaccination costs and willingness-to-pay thresholds, the level of vaccination coverage necessary to sustain herd-immunity, the price at which vaccination is cost-effective and is cost-saving, and the sensitivity of our results to parameter uncertainty. We compared two vaccine efficacy scenarios, one a more optimistic scenario and another based on the recent lower-than-expected efficacy from the latest clinical trials. We found that herd-immunity may be achieved by vaccinating 82% (95% CI 58-100%) of the population at a vaccine efficacy of 70%. At this efficacy, vaccination may be cost-effective for vaccination costs up to US$ 534 (95% CI $369-1008) per vaccinated individual and cost-saving up to $204 (95% CI $39-678). At the latest clinical trial estimates of an average of 30% vaccine efficacy, vaccination may be cost-effective and cost-saving at costs of up to $237 (95% CI $159-512) and $93 (95% CI $15-368), respectively. Our model provides an assessment of the cost-effectiveness of dengue vaccination in Brazil and incorporates the effect of herd immunity into dengue vaccination cost-effectiveness. Our results demonstrate that at the relatively low vaccine efficacy from the recent Phase 2b dengue vaccine trials, age-targeted vaccination may still be cost-effective provided the total vaccination cost is sufficiently low.
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
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.
PLoS ONE 01/2013; 8(4):e59768. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study describes the main features of pandemic influenza A (H1N1) in Brazil during 2009. Brazil is a large country that extends roughly from latitudes 5ºN to 34ºS. Brazil has tropical and sub-tropical climates, a heterogeneous population distribution, and intense urbanization in the southern portions of the country and along its Atlantic coast. Our analysis points to a wide variation in infection rates throughout the country, and includes both latitudinal effects and strong variations in detection rates. Two states (out of a total of 23) were responsible for 73% of all cases reported. Real time reproduction numbers demonstrate that influenza transmission was sustained in the country, beginning in May of 2009. Finally, this study discusses the challenges in understanding the infection dynamics of influenza and the adequacy of Brazil's influenza monitoring system.
Cadernos de saúde pública / Ministério da Saúde, Fundação Oswaldo Cruz, Escola Nacional de Saúde Pública 07/2012; 28(7):1325-36. · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined the cost-effectiveness of the quadrivalent HPV vaccine for the pre-adolescent female population of Brazil. Using demographic, epidemiological and cancer data, we developed a dynamic individual-based model representing the natural history of HPV/cervical cancer as well as the impact of screening and vaccination programmes. Assuming the current screening strategies, we calculated the incremental cost-effectiveness ratio (ICER) for cohorts with and without vaccination taking into account different combinations of vaccination coverage (50%, 70%, 90%) and cost per vaccinated woman (US$25, US$55, US$125, US$556). The results varied from cost-saving (coverage 50% or 70% and cost per vaccinated woman US$25) to 5950 US$/QALY (coverage 90% and cost per vaccinated 556 US$). In a scenario in which a booster shot was needed after 10 years in order to secure lifelong protection, the ICER resulted in 13,576 US$/QALY. Considering the very cost-effective and cost-effective thresholds based on Brazil's GDP per capita, apart from the booster scenario which would be deemed cost-effective, all the other scenarios would be deemed very cost-effective. Both the cost per dose of vaccine and discount rate (5%) had an important impact on the results. Vaccination in addition to the current screening programme is likely to save years of life and, depending on the cost of vaccination, may even save resources. Price negotiations between governments and manufacturers will be paramount in determining that the vaccine not only represents good value for money, but is also affordable in middle-income countries like Brazil.
[Show abstract][Hide abstract] ABSTRACT: Although it is the second leading cause of deaths worldwide, the cerebrovascular accident (CVA) has shown a significant reduction in mortality rates in recent decades.
To evaluate the trend of CVA mortality rate in Brazil, in both sexes, older than 30 years old, between 2000 and 2009.
Population data were obtained from the database of the Brazilian Institute of Geography and Statistics (IBGE) and deaths through the Mortality Information System of the Health Surveillance Secretariat of the Ministry of Health, and included codes I60 to I69 according to 10th International Classification of Diseases. We calculated the incidence of deaths/1,000 inhabitants, gross and standardized mortality rates /100,000 inhabitants. The modeling of the trend of rates was performed using regression models.
There was an increase in mortality until 2006, followed by a decline until 2009, when the incidence was the lowest. Comparing the years 2000 and 2009, there is a downward trend in standardized mortality rate in both sexes (male = -14.69% and female = -17%) and total (-14.99%), with fluctuations during the period. Between 30 and 49 years in both sexes, there was a trend of continuous and linear decrease in mortality rate, while the other age groups showed a curvilinear function, leading to an effective decrease in values.
There was a downward trend in mortality in all age groups and both sexes. The reduction in gross mortality rate was more pronounced in males, while the standardized mortality rate showed a greater reduction in females.
Arquivos brasileiros de cardiologia 04/2012; 98(6):519-27. · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To project the clinical and economic outcomes of a genotype assay for selection of third-line antiretroviral therapy (ART) in resource-limited settings, as per the planned international A5288 trial (MULTI-OCTAVE).
We used the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-International Model to compare three strategies for patients who have failed second-line ART in South Africa: sustained second-line: no genotype assay, all patients remain on second-line ART; A5288: genotype to determine the resistance profile and assign an appropriate regimen; or population-based third-line: no genotype, all patients switch to a potent third-line regimen. Model inputs are from published data in South Africa. Resistance profiles, ART regimens, and efficacy data were those used for trial planning.
Projected life expectancy for sustained second-line, A5288, and population-based third-line are 61.1, 103.8, and 104.2 months. Compared to sustained second-line ($12 ,460), per person lifetime costs increase for the A5288 ($39, 250) and population-based ($44, 120) strategies. The incremental cost-effectiveness ratio of A5288, compared to sustained second-line, is $7500/year of life saved (YLS), and for population-based third-line, compared to A5288, is $154 ,500/YLS. In the A5288 strategy, very late presentation to care, coupled with lengthy delays to obtain the genotype, dramatically reduces 5-year survival, making the population-based third-line strategy more attractive.
We project that, whereas the public health approach to third-line therapy is unaffordable, genotype assays and third-line ART in resource-limited settings will increase survival and be cost-effective compared to the population-based approach, supporting the value of an efficacy study.
AIDS (London, England) 02/2012; 26(9):1083-93. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11-6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11-0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.
International Journal of STD & AIDS 01/2012; 23(1):12-7. · 1.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses.
Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively.
Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained.
PLoS ONE 01/2012; 7(6):e39310. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Due to the recent widespread availability of highly active antiretroviral therapy (HAART) in middle-income countries, there has been an increase in life expectancy for women on HAART, but no corresponding decrease in cervical cancer incidence. This study evaluates the optimal cervical cancer screening strategy for HIV-infected women in a middle-income country. We developed a mathematical model, which simulates the natural history of the HPV infection, as well as the HIV-mediated immunosupression among women in Brazil. Our model was calibrated using data from the IPEC/FIOCRUZ Women's HIV-infected cohort. The model compares the lifetime effects, costs and cost-effectiveness of strategies combining cytology, HPV DNA test and colposcopy at different screening intervals for different CD4 count strata (27 strategies in total). We found that the strategy with the best cost-effectiveness profile (cost-effectiveness ratio-U$4,911/year of life saved [YLS] and probability of being cost-effective-86%) was HPV testing followed by cytology triage every year for all HIV infected women, considering a very cost-effective threshold given by Brazil's GDP per capita (US$8,625/YLS). The results were robust to changes in the input parameters as demonstrated in one-way, scenario, threshold and probabilistic sensitivity analysis. Our study indicates that annual HPV testing followed by cytology triage for all HIV-infected women is likely to be very cost-effective in a middle-income country like Brazil. The results reflect the synergic effect of using a highly sensitive screening test (HPV DNA test) in sequence with a highly specific test (cytology).
International Journal of Cancer 09/2011; 131(2):E96-104. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, we showed that infection with dengue virus increases the locomotor activity of Aedes aegypti females. We speculate that the observed increased locomotor activity could potentially increase the chances of finding a suitable host and, as a consequence, the relative biting rate of infected mosquitoes. We used a mathematical model to investigate the impact of the increased locomotor activity by assuming that this activity translated into an increased biting rate for infected mosquitoes. The results show that the increased biting rate resulted in dengue outbreaks with greater numbers of primary and secondary infections and with more severe biennial epidemics.
Memórias do Instituto Oswaldo Cruz 09/2011; 106(6):755-8. · 1.36 Impact Factor