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.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Estimating the extent of underreporting of mortality among HIV-infected individuals in Rio de Janeiro, Brazil.

Non-HIV-related causes of death have been increasing after the introduction of highly active antiretroviral therapy. Underlying and contributing causes of death were assessed in respect to the presence/absence of HIV/AIDS among HIV-infected/AIDS patients in Rio de Janeiro, Brazil. Demographic variables (age, gender, ethnicity, and schooling) and CD4 cell counts closest to death were assessed through logistic regression models comparing those who did not have with those who had HIV/AIDS mentioned on the death certificate. The linkage with the two cohorts identified 1249 records, of which 370 (29.6%) did not have HIV/AIDS listed on any field of the death certificate [77 (20.8%) attributed to undefined and 72 (19.5%) to external causes]. After excluding external causes, 25.3% still did not have HIV/AIDS listed on the death certificate. Multiple logistic regression analysis showed that age >40 years (OR = 2.09; 95%CI = 1.49-2.93; p < 0.001) and CD4 cell count closest to the date of death (OR = 1.15; 95% CI = 1.07-1.23; p < 0.001 for 100 cell increase) were associated with an increased probability of not having HIV/AIDS mentioned on the death certificate, when external causes were excluded. Mortality among HIV-infected individuals is underreported in the Rio de Janeiro Mortality Registry, particularly among older individuals and those with higher CD4 counts. Physicians should be aware of the changing patterns of mortality among HIV individuals, and public health officials should regularly perform linkages between all-cause mortality and available HIV-infected patients databases, such as AIDS registries and large cohort studies.

Rates and reasons for early change of first HAART in HIV-1-infected patients in 7 sites throughout the Caribbean and Latin America.

BACKGROUND: HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%-70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. METHODOLOGY: Antiretroviral-naïve patients >or= 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. PRINCIPAL FINDINGS: Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31-44), and median CD4 count was 105 cells/uL (IQR, 38-200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15-17%) and 28% (95% CI 27-29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1-2.6) and 2.1 (95% CI 1.7-2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1-1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens. CONCLUSIONS: Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation.

Risk-based assessment does not distinguish between recent and chronic HIV-1 infection in Rio de Janeiro, Brazil

This study investigated the risk factors associated with recent and chronic HIV infections among individual attending a voluntary counseling and testing (VCT) site in Rio de Janeiro, Brazil. In a cross-sectional study, recent HIV infections were detected by the sensitive/less-sensitive test, using Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) strategy, and compared to chronic HIV infection and HIV negative individuals. Seroincidence was estimated and risk factors associated with recent and chronic infections were assessed using multinomial logistic regression. Among the 7,379 individuals tested between June 2006 and April 2007, the overall prevalence and incidence of HIV infection were 7.5 percent; and 1.39/100 PY, respectively. In multivariate analysis, having a HIV positive steady partner was a risk factor for recent and for chronic HIV infection for MSM, heterosexual male and women. No differences in risk factors for recent and chronic infections were found between MSM and heterosexual males. Among women, chronic infected individuals were more likely than HIV negatives to be older. Recently HIV infected women were more likely than HIV negatives to be less educated; and more likely than HIV negatives and chronically infected to report having more partners. Routinely used risk-based assessment in testing centers in Brazil lack sensitivity to distinguish between recent and chronic infections, particularly among MSM and heterosexual males. Steady relationships and serosorting may be playing a key role in maintaining the HIV epidemics in Brazil.

Temporal changes in causes of death among HIV-infected patients in the HAART era in Rio de Janeiro, Brazil.

BACKGROUND: The widespread use of highly active antiretroviral therapy (HAART) has led to marked decreases in death rates in Brazil in HIV-infected individuals. Nonetheless, there are scarce data on specific causes of death. METHODS: Death rates from a cohort of HIV-infected patients in Rio de Janeiro, Brazil, were analyzed in 2-year periods, from 1997 to 2006. Poisson models and survival models accounting for competing risks were used to assess association of covariables. A standardized validated algorithm was used to ascertain specific causes of death. RESULTS: Of the 1538 eligible patients, 226 (14.7%) died during the study period, corresponding to a mortality rate of 3.2 per 100 person-years. The median follow-up time was 4.61 years (interquartile range = 5.63 years) and the loss to follow-up rate was 2.4 per 100 person-years. Overall, 98 (43.4%) were classified as non-AIDS-related causes. Although opportunistic infections were the leading causes of death (37.6%), deaths due to AIDS-related causes declined significantly over time (P < 0.01). In the most recent period (2005-2006), the rate of non-AIDS-related causes of deaths was higher than that of AIDS-related causes of death. CONCLUSIONS: In the HAART era, there has been a significant change in causes of death among HIV-infected patients in Rio de Janeiro. As access to HAART improves, integration with other public programs will become critically important for the long-term success of HIV/AIDS programs in developing countries.

Mortality during the first year of potent antiretroviral therapy in HIV-1-infected patients in 7 sites throughout Latin America and the Caribbean.

BACKGROUND: Although nearly 2 million people live with HIV in Latin America and the Caribbean, mortality rates after initiation of highly active antiretroviral therapy (HAART) have not been well described. METHODS: Five thousand one hundred fifty-two HIV-infected, antiretroviral-naive adults from clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru starting HAART during 1996-2007 were included. First-year mortality rates and their association with demographics, regimen, baseline CD4, and clinical stage were assessed. RESULTS: Overall 1-year mortality rate was 8.3% [95% confidence interval (CI): 7.6% to 9.1%], although variable across sites: 2.6%, 3.7%, 6.0%, 13.0%, 10.8%, 3.5%, and 9.8% for clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru, respectively. Eighty percent of deaths occurred within the first 6 months. Median baseline CD4 was 107 cells per milliliter, ranging from 79 (Peru) to 163 (Argentina). Mortality estimates adjusting for CD4 were similar across sites (1.1%-2.8% for CD4 = 200), except for Haiti, 7.5%, and Honduras, 7.0%. Death was associated with lower CD4 [adjusted hazard ratio for CD4 = 200 vs. CD4 = 50 was 0.58; 95% CI: 0.40 to 0.85] and clinical AIDS (hazard ratio = 3.1; 95% CI: 2.1 to 4.5). CONCLUSIONS: Mortality rates were similar to those reported elsewhere for resource-limited settings. Disease stage at HAART initiation, treatment eligibility criteria, program age, and background mortality rates may explain some variability in prognosis between sites.

Risk-based assessment does not distinguish between recent and chronic HIV-1 infection in Rio de Janeiro, Brazil.

This study investigated the risk factors associated with recent and chronic HIV infections among individual attending a voluntary counseling and testing (VCT) site in Rio de Janeiro, Brazil. In a cross-sectional study, recent HIV infections were detected by the sensitive/less-sensitive test, using Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) strategy, and compared to chronic HIV infection and HIV negative individuals. Seroincidence was estimated and risk factors associated with recent and chronic infections were assessed using multinomial logistic regression. Among the 7,379 individuals tested between June 2006 and April 2007, the overall prevalence and incidence of HIV infection were 7.5%; and 1.39/100 PY, respectively. In multivariate analysis, having a HIV positive steady partner was a risk factor for recent and for chronic HIV infection for MSM, heterosexual male and women. No differences in risk factors for recent and chronic infections were found between MSM and heterosexual males. Among women, chronic infected individuals were more likely than HIV negatives to be older. Recently HIV infected women were more likely than HIV negatives to be less educated; and more likely than HIV negatives and chronically infected to report having more partners. Routinely used risk-based assessment in testing centers in Brazil lack sensitivity to distinguish between recent and chronic infections, particularly among MSM and heterosexual males. Steady relationships and serosorting may be playing a key role in maintaining the HIV epidemics in Brazil.

Validation of a hierarchical deterministic record-linkage algorithm using data from 2 different cohorts of human immunodeficiency virus-infected persons and mortality databases in Brazil.

Loss to follow-up is a major source of bias in cohorts of patients with human immunodeficiency virus (HIV) and could lead to underestimation of mortality. The authors developed a hierarchical deterministic linkage algorithm to be used primarily with cohorts of HIV-infected persons to recover vital status information for patients lost to follow-up. Data from patients known to be deceased in 2 cohorts in Rio de Janeiro, Brazil, and data from the Rio de Janeiro State mortality database for 1999-2006 were used to validate the algorithm. A fully automated procedure yielded a sensitivity of 92.9% and specificity of 100% when no information was missing. When the automated procedure was combined with clerical review, in a scenario of 5% death prevalence and 20% missing mothers' names, sensitivity reached 96.5% and specificity 100%. In a practical application, the algorithm significantly increased death rates and decreased the rate of loss to follow-up in the cohorts. The finding that 23.9% of matched records did not give HIV or acquired immunodeficiency syndrome as the cause of death reinforces the need to search all-cause mortality databases and alerts for possible underestimation of death rates. These results indicate that the algorithm is accurate enough to recover vital status information on patients lost to follow-up in cohort studies.

Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration.

AIMS: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS: The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS: Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS: Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Increase in non-AIDS related conditions as causes of death among HIV-infected individuals in the HAART era in Brazil.

BACKGROUND: In 1996, Brazil became the first developing country to provide free and universal access to HAART. Although a decrease in overall mortality has been documented, there are no published data on the impact of HAART on causes of death among HIV-infected individuals in Brazil. We assessed temporal trends of mortality due to cardiovascular diseases (CVD), diabetes mellitus (DM) and other conditions generally not associated with HIV-infection among persons with and without HIV infection in Brazil between 1999 and 2004. METHODOLOGY/PRINCIPAL FINDINGS: Odds ratios were used to compare causes of death in individuals who had HIV/AIDS listed on any field of the death certificate with those who did not. Logistic regression models were fitted with generalized estimating equations to account for spatial correlation; co-variables were added to the models to control for potential confounding. Of 5,856,056 deaths reported in Brazil between 1999 and 2004 67,249 (1.15%) had HIV/AIDS listed on the death certificate and non-HIV-related conditions were listed on 16.3% in 1999, increasing to 24.1% by 2004 (p<0.001). The adjusted average yearly increases were 8% and 0.8% for CVD (p<0.001), and 12% and 2.8% for DM (p<0.001), for those who had and did not have HIV/AIDS listed on the death certificate, respectively. Similar results were found for these conditions as underlying causes of death. CONCLUSIONS/SIGNIFICANCE: In Brazil between 1999 and 2004 conditions usually considered not to be related to HIV-infection appeared to become more likely causes of death over time than reported causes of death among individuals who had HIV/AIDS listed on the death certificate than in those who did not. This observation has important programmatic implications for developing countries that are scaling-up access to antiretroviral therapy.

Discordant responses to potent antiretroviral treatment in previously naive HIV-1-infected adults initiating treatment in resource-constrained countries: the antiretroviral therapy in low-income countries (ART-LINC) collaboration.

OBJECTIVES: To assess the frequency of and risk factors for discordant responses at 6 months on highly active antiretroviral therapy (HAART) in previously treatment-naive HIV patients from resource-limited countries. METHODS: The Antiretroviral Therapy in Low-Income Countries Collaboration is a network of clinics providing care and treatment to HIV-infected patients in Africa, Latin America, and Asia. Patients who initiated therapy between 1996 and 2004, were aged 16 years or older, and had a baseline CD4 cell count were included in this analysis. Responses were defined based on plasma viral load (PVL) and CD4 cell count at 6 months as complete virologic and immunologic (VR(+)IR(+)), virologic only (VR(+)IR(-)), immunologic only (VR(-)IR(+)), and nonresponse (VR(-)IR(-)). Multinomial logistic regression was used to assess the association between therapy responses and clinical and demographic variables. RESULTS: Of the 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VR(+)IR(+), 364 (19.0%) were VR(+)IR(-), 283 (14.8%) were (VR(-)IR(+)), and 193 (10.1%) were VR(-)IR(-). OF THE 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VRIR, 364 (19.0%) were VRIR, 283 (14.8%) were (VRIR), and 193 (10.1%) were VRIR. Compared with complete responders, virologic-only responders were older, had a higher baseline CD4 cell count, had a lower baseline PVL, and were more likely to have received a nonstandard HAART regimen; immunologic-only responders were younger, had a lower baseline CD4 cell count, had a higher baseline PVL, and were more likely to have received a protease inhibitor-based regimen. CONCLUSIONS: The frequency of and risk factors for discordant responses were comparable to those observed in developed countries. Longer follow-up is needed to assess the long-term impact of discordant responses on mortality in these resource-limited settings.

Waterborne toxoplasmosis, Brazil, from field to gene.

Water was the suspected vehicle of Toxoplasma gondii dissemination in a toxoplasmosis outbreak in Brazil. A case-control study and geographic mapping of cases were performed. T. gondii was isolated directly from the implicated water and genotyped as SAG 2 type I.

Predictors of virologic failure in HIV-1-infected patients starting highly active antiretroviral therapy in Porto Alegre, Brazil.

OBJECTIVE: To assess predictors of virologic response 6 months after initiation of highly active antiretroviral therapy (HAART) in a cohort of HIV-infected patients in Brazil. METHODS: Treatment-naive patients who started HAART between 1996 and 2004 and had information on viral load at 3-9 months were included. Information was collected on demographic characteristics, antiretroviral regimen, adherence, AIDS diagnosis, baseline CD4 cell count, and viral load. Virologic failure (VF) was defined as viral load > or =400 copies/mL at 6 months or death before completion of 6 months of therapy. RESULTS: Among 454 patients who met the inclusion criteria, VF occurred in 127 (28.0%). In univariate analysis, VF was associated with younger age (median 34 vs. 37 years, P = 0.003), AIDS diagnosis (relative risk [RR] 1.18, P = 0.009), higher baseline viral load (5.34 vs. 5.00, P = 0.0002), lower baseline CD4 cell count (86 vs. 182, P = 0.006), nonadherence (RR 1.39, P < 0.0001), regimen containing 1 single protease inhibitor, as compared with ritonavir-boosted regimens (odds ratio [OR] 8.5, P < 0.0001), and year therapy initiated before 1999 (P < 0.0001). To minimize the systematic effect of therapy indication, we analyzed the subset of 158 patients with CD4 count < or =200 cells/microL who started therapy after 1999. After adjusting for age, education, adherence, regimen, and baseline viral load, nonadherence (OR 8.78, P = 0.02), and fewer years of education (OR 6.05, P = 0.05) remained associated with VF. CONCLUSIONS: A significant improvement was found in virologic suppression over time, consistent with the introduction of nonnucleoside reverse transcriptase inhibitors and ritonavir-boosted regimens into clinical practice. With currently available therapies, compliance and education were shown to be predictors of virologic response, particularly in more immunocompromised patients.