Cardiovascular disease among people living with HIV in Brazil.

OBJECTIVES: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. METHODS: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. RESULTS: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01). CONCLUSIONS: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

OBJECTIFS: Il existe peu de données sur les maladies cardiovasculaires (MCV) chez les personnes vivant avec le VIH (PVVIH) dans les pays à ressources limitées. Nous avons évalué les facteurs associés aux MCV et l'impact des MCV prévalentes sur la mortalité toutes causes confondues des PVVIH sous le traitement antirétroviral au Brésil. MÉTHODES: Régression des risques concurrente pour évaluer les facteurs associés aux MCV et à la mortalité toutes causes confondues dans l'étude de cohorte VIH-Brésil entre 2003 et 2014. RÉSULTATS: Parmi 5.614 patients, le taux de MCV était de 3,5 (intervalle de confiance à 95% [IC95%] 2,9-4,3) pour 1.000 personnes-années. Les MCV étaient associées à un âge plus avancé (rapport de risque ajusté [aHR] 6,4 chez les ≥55 ans versus chez les <35 ans, IC95%: 2,5-16,3 ; p <0,01), race noire (aHR: 1,8 versus race blanche, IC95%: 1,0-3,1 ; p = 0,04), MCV passée (aHR: 3,0 versus pas de MCV passée, IC95%: 1,4-6,2 ; p <0,01), hypertension (aHR: 1,8 versus pas d'hypertension, IC95%: 1,0-3,1 ; p = 0,04), dyslipidémie de grade élevé (aHR 9,3 versus absence de dyslipidémie de grade élevé, IC95%: 6,0-14,6 ; p <0,01), tabagisme (aHR 2,4 versus n'avoir jamais fumé, IC95%: 1,2-5,0 ; p = 0,02) et faible nombre de CD4 au nadir (aHR: 1,8 pour 100-250 cellules/mm3 versus >250 cellules/mm3 , IC95%: 1,0-3,2 ; p = 0,05). Le taux de décès était de 16,6 (IC95%: 15,1-18,3) pour 1.000 personnes-années. Le décès était fortement associé à un événement MCV antérieur (aHR: 1,7 versus aucun événement MCV antérieur, IC95%: 1,1-2,7 ; p = 0,01). CONCLUSIONS: Les facteurs traditionnels et spécifiques au VIH associés aux MCV chez les PVVIH au Brésil sont similaires à ceux identifiés chez les PVVIH dans les pays à revenu élevé. Les PVVIH au Brésil ayant des antécédents de MCV ont un risque élevé de décès. Les soins et le traitement des MCV restent des priorités pour les PVVIH au Brésil à mesure que cette population vieillit et que l'utilisation des thérapies antirétrovirales augmente.

Self-audits as alternatives to travel-audits for improving data quality in the Caribbean, Central and South America network for HIV epidemiology.

INTRODUCTION: Audits play a critical role in maintaining the integrity of observational cohort data. While previous work has validated the audit process, sending trained auditors to sites ("travel-audits") can be costly. We investigate the efficacy of training sites to conduct "self-audits." METHODS: In 2017, eight research groups in the Caribbean, Central, and South America network for HIV Epidemiology each audited a subset of their patient records randomly selected by the data coordinating center at Vanderbilt. Designated investigators at each site compared abstracted research data to the original clinical source documents and captured audit findings electronically. Additionally, two Vanderbilt investigators performed on-site travel-audits at three randomly selected sites (one adult and two pediatric) in late summer 2017. RESULTS: Self- and travel-auditors, respectively, reported that 93% and 92% of 8919 data entries, captured across 28 unique clinical variables on 65 patients, were entered correctly. Across all entries, 8409 (94%) received the same assessment from self- and travel-auditors (7988 correct and 421 incorrect). Of 421 entries mutually assessed as "incorrect," 304 (82%) were corrected by both self- and travel-auditors and 250 of these (72%) received the same corrections. Reason for changing antiretroviral therapy (ART) regimen, ART end date, viral load value, CD4%, and HIV diagnosis date had the most mismatched corrections. CONCLUSIONS: With similar overall error rates, findings suggest that data audits conducted by trained local investigators could provide an alternative to on-site audits by external auditors to ensure continued data quality. However, discrepancies observed between corrections illustrate challenges in determining correct values even with audits.

Trends and predictors of non-communicable disease multimorbidity among adults living with HIV and receiving antiretroviral therapy in Brazil.

INTRODUCTION: People living with HIV (PLHIV) on antiretroviral therapy (ART) experience high rates of non-communicable diseases (NCDs). These co-morbidities often accumulate and older adults may suffer from multimorbidity. Multimorbidity has been associated with loss of quality of life, polypharmacy, and increased risk of frailty and mortality. Little is known of the trends or predictors NCD multimorbidity in PLHIV in low- and middle-income countries. METHODS: We examined NCD multimorbidity in adult PLHIV initiating ART between 2003 and 2014 using a multi-site, observational cohort in Brazil. NCDs included cardiovascular artery disease, hyperlipidemia (HLD), diabetes, chronic kidney disease, cirrhosis, osteoporosis, osteonecrosis, venous thromboembolism and non-AIDS-defining cancers. Multimorbidity was defined as the incident accumulation of two or more unique NCDs. We used Poisson regression to examine trends and Cox proportional hazard models to examine predictors of multimorbidity. RESULTS: Of the 6206 adults, 332 (5%) developed multimorbidity during the study period. Parallel to the ageing of the cohort, the prevalence of multimorbidity rose from 3% to 11% during the study period. Older age, female sex (adjusted hazard ratio (aHR) = 1.30 (95% confidence interval (CI) 1.03 to 1.65)) and low CD4 nadir (<100 vs. ≥200 cells/mm3 aHR = 1.52 (95% CI: 1.15 to 2.01)) at cohort entry were significantly associated with increased risk of multimorbidity. Among patients with incident multimorbidity, the most common NCDs were HLD and diabetes; however, osteoporosis was also frequent in women (16 vs. 35% of men and women with multimorbidity respectively). CONCLUSIONS: Among adult PLHIV in Brazil, NCD multimorbidity increased from 2003 to 2014. Females and adults with low CD4 nadir were at increased risk in adjusted analyses. Further studies examining prevention, screening and management of NCDs in PLHIV in low- and middle-income countries are needed.

Hyperglycemia during tuberculosis treatment increases morbidity and mortality in a contemporary cohort of HIV-infected patients in Rio de Janeiro, Brazil.

BACKGROUND: Hyperglycemia occurs in tuberculosis (TB), but the long-term impact is unknown. We estimated the prevalence of hyperglycemia and compared the TB treatment outcomes and 1-year mortality rate according to the glycemic status noted during TB treatment. METHODS: We conducted a retrospective cohort analysis of adult patients who had TB and HIV coinfection and started receiving TB treatment at the Instituto Nacional de Infectologia Evandro Chagas, Brazil, between 2010-2015. Diabetes Mellitus (DM) and hyperglycemia were defined according to the American Diabetes Association. After excluding for known DM at baseline, the proportion of participants who developed new-onset DM after TB treatment was assessed. TB outcome was classified as successful or adverse (i.e., treatment failure, abandonment, and death). Kaplan-Meier survival curves were compared by the log-rank test based on the glycemic status of patients. Multivariate Cox regression models were used to assess the association between hyperglycemia and 1-year mortality. Two-sided p values <0.05 were considered statistically significant. RESULTS: We identified 414 euglycemic patients (87.5%), 49 hyperglycemic patients (10.3%), and 10 patients with known DM (2.1%). Diabetic patients were older compared to the euglycemic and hyperglycemic patients (47.9 vs. 37 vs. 39.7 years, respectively, p=0.001). Diabetic patients frequently had cavitation on chest image compared to hyperglycemic and euglycemic patients (50% vs. 23.4% vs. 15.3%, p=0.007, respectively). Hyperglycemic patients had more new-onset DM at follow-up compared to euglycemic (22 vs. 1; p<0001). Hyperglycemia was associated with adverse outcomes (71.4% vs. 24.6%, p<0.0001) compared to euglycemia. Crude 1-year mortality was significantly higher in patients with hyperglycemia compared with euglycemia (48.9% vs. 7.9%; unadjusted HR: 5.79 (3.74-8.96)). In the adjusted Cox models, hyperglycemia remained a significant factor for increased 1-year mortality (adjusted HR: 3.72 (2.17-6.38)]. CONCLUSIONS: Hyperglycemia frequently occurs in HIV-infected patients who commence TB treatment, and it increases the risks of adverse TB outcomes and 1-year mortality. Glucose testing during TB treatment detects patients at risk of adverse outcomes.

Effects of antiretroviral treatment and nadir CD4 count in progression to cardiovascular events and related comorbidities in a HIV Brazilian cohort: a multi-stage approach.

The use of highly active antiretroviral therapy has resulted in changes of comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS-related events. The occurrence of cardiovascular events is greater in PLHIV, but the mechanism responsible for it is still controversial. This article aimed to investigate factors associated with the progression to cardiovascular events in PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio de Janeiro-Brazil. Clinical progression was stratified in five states: No comorbidities (s1), arterial hypertension (s2), lipid abnormalities (s3), hypertension and lipid abnormalities (s4) and major cardiovascular events (stroke, coronary artery disease, thrombosis or death) (s5). Semi-Markov models evaluated the effects of cardiovascular traditional factors, treatment and clinical covariates on transitions between these states. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided. In addition to traditional factors (age, sex, educational level and skin color), the development of one comorbidity (lipid abnormalities or hypertension) increased in patients with low nadir CD4 (<50 cells/mm3), (HR = 1.59, CI 1.11-2.28 and 1.36, CI 1.11-1.66, respectively). The risk to experience a second comorbidity (s3→s4) increased 75% with low nadir CD4. Age was the only factor that increased the risk of major cardiovascular events once having lipid abnormalities with or without hypertension (s3,s4→s5). The prolonged use of certain antiretroviral drugs (abacavir, didanosine, ritonavir, lopinavir, amprenavir and fosamprenavir) increased the risk of direct transition (s1→s5) to major cardiovascular events (HR = 5.29, CI 1.16-24.05). This analysis suggests that prolonged use of certain antiretroviral drugs led directly to major cardiovascular events, while low nadir CD4 only affected the occurrence of lipid abnormalities and hypertension. Management strategies, including rational use of complex exams (such as, computed-tomography angiography), statins and antihypertensives, should be developed based on the distinct roles of antiretroviral use and of HIV infection itself on the progression to cardiovascular events.

Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy.

Increased access to highly active antiretroviral therapy (HAART) by human immunodeficiency virus postive (HIV⁺) individuals has become a reality worldwide. In Brazil, HAART currently reaches over half of HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. In this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV⁺ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

Mortality in patients with HIV-1 and tuberculosis co-infection in Rio de Janeiro, Brazil - associated factors and causes of death.

BACKGROUND: Tuberculosis is the most frequent opportunistic infection and the leading cause of death among persons living with HIV in several low and middle-income countries. Mortality rates during tuberculosis treatment and death causes among HIV-1/TB co-infected patients may differ based on the immunosuppression severity, timing of diagnosis and prompt initiation of tuberculosis and antiretroviral therapy. METHODS: This was a retrospective observational study conducted in the clinical cohort of patients with HIV-1/Aids of the National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro, Brazil. All HIV-1 infected patients who started combination antiretroviral therapy up to 30 days before or within 180 days after the start of tuberculosis treatment from 2000 to 2010 were eligible. Causes of death were categorized according to the "Coding Causes of Death in HIV" (CoDe) protocol. The Cox model was used to estimate the hazard ratio (HR) of selected mortality variables. RESULTS: A total of 310 patients were included. Sixty-four patients died during the study period. Mortality rate following tuberculosis treatment initiation was 44 per 100 person-years within the first 30 days, 28.1 per 100 person-years within 31 and 90 days, 6 per 100 person-years within 91 and 365 days and 1.6 per 100 person-years after 365 days. Death probability within one year from tuberculosis treatment initiation was approximately 13%. In the adjusted analysis the associated factors with mortality were: CD4 ≤ 50 cells/mm3 (HR: 3.10; 95% CI: 1.720 to 5.580; p = 0.00); mechanical ventilation (HR: 2.81; 95% CI: 1.170 to 6.760; p = 0.02); and disseminated tuberculosis (HR: 3.70; 95% CI: 1.290 to 10.590, p = 0.01). Invasive bacterial disease was the main immediate cause of death (46.9%). CONCLUSION: Our results evidence the high morbidity and mortality among patients co-infected with HIV-1 and tuberculosis in Rio de Janeiro, Brazil. During the first year following tuberculosis diagnosis, mortality was the highest within the first 3 months, being invasive bacterial infection the major cause of death. In order to successfully intervene in this scenario, it is utterly necessary to address the social determinants of health contributing to the inequitable health care access faced by this population.

Thirty-day Readmission Rates in an HIV-infected Cohort From Rio de Janeiro, Brazil.

BACKGROUND: The 30-day readmission rate is an indicator of the quality of hospital care and transition to the outpatient setting. Recent studies suggest HIV infection might increase the risk of readmission although estimates of 30-day readmission rates are unavailable among HIV-infected individuals living in middle/low-income settings. Additionally, factors that may increase readmission risk in HIV-infected populations are poorly understood. METHODS: Thirty-day readmission rates were estimated for HIV-infected adults from the Instituto Nacional de Infectologia Evandro Chagas/Fiocruz cohort in Rio de Janeiro, Brazil, from January 2007 to December 2013. Cox regression models were used to evaluate factors associated with the risk of 30-day readmission. RESULTS: Between January 2007 and December 2013, 3991 patients were followed and 1861 hospitalizations were observed. The estimated 30-day readmission rate was 14% (95% confidence interval: 12.3 to 15.9). Attending a medical visit within 30 days after discharge (adjusted hazard ratio [aHR] = 0.73, P = 0.048) and being hospitalized in more recent calendar years (aHR = 0.89, P = 0.002) reduced the risk of 30-day readmission. In contrast, low CD4 counts (51-200 cells/mm³: aHR = 1.70, P = 0.024 and ≤ 50 cells/mm³: aHR = 2.05, P = 0.003), time since HIV infection diagnosis ≥10 years (aHR = 1.58, P = 0.058), and leaving hospital against medical advice (aHR = 2.67, P = 0.004) increased the risk of 30-day readmission. CONCLUSIONS: Patients with advanced HIV/AIDS are most at risk of readmission and should be targeted with prevention strategies to reduce this risk. Efforts to reduce discharge against medical advice and to promote early postdischarge medical visit would likely reduce 30-day readmission rates in our population.

Hospitalization rates, length of stay and in-hospital mortality in a cohort of HIV infected patients from Rio de Janeiro, Brazil

Abstract In this study, we evaluated trends in hospitalization rates, length of stay and in-hospital mortality in a cohort of HIV-infected patients in Rio de Janeiro, Brazil, from 2007 through 2013. Among the 3991 included patients, 1861 hospitalizations occurred (hospitalization rate of 10.44/100 person-years, 95% confidence interval 9.98-10.93/100 person-years). Hospitalization rates decreased annually (per year incidence rate ratio 0.92, 95% confidence interval 0.89-0.95) as well as length of stay (median of 15 days in 2007 vs. 11 days in 2013, p-value for trend < 0.001), and in-hospital mortality (13.4% in 2007 to 8.1% in 2013, p-value for trend = 0.053). Our results show that, in a middle-income setting, hospitalization rates are decreasing over time and non-AIDS hospitalizations are currently more frequent than those related to AIDS. Notwithstanding, compared with high-income settings, our patients had longer length of stay and higher in-hospital mortality. Further studies addressing these outcomes are needed to provide information that may guide protocols and interventions to further reduce health-care costs and in-hospital mortality.

Hospitalization rates, length of stay and in-hospital mortality in a cohort of HIV infected patients from Rio de Janeiro, Brazil.

In this study, we evaluated trends in hospitalization rates, length of stay and in-hospital mortality in a cohort of HIV-infected patients in Rio de Janeiro, Brazil, from 2007 through 2013. Among the 3991 included patients, 1861 hospitalizations occurred (hospitalization rate of 10.44/100 person-years, 95% confidence interval 9.98-10.93/100 person-years). Hospitalization rates decreased annually (per year incidence rate ratio 0.92, 95% confidence interval 0.89-0.95) as well as length of stay (median of 15 days in 2007 vs. 11 days in 2013, p-value for trend<0.001), and in-hospital mortality (13.4% in 2007 to 8.1% in 2013, p-value for trend=0.053). Our results show that, in a middle-income setting, hospitalization rates are decreasing over time and non-AIDS hospitalizations are currently more frequent than those related to AIDS. Notwithstanding, compared with high-income settings, our patients had longer length of stay and higher in-hospital mortality. Further studies addressing these outcomes are needed to provide information that may guide protocols and interventions to further reduce health-care costs and in-hospital mortality.

Poor retention in early care increases risk of mortality in a Brazilian HIV-infected clinical cohort.

Retention in early HIV care has been associated with decreased mortality and improved viral suppression, however the consequences of poor retention in early care in Brazil remain unknown. We assessed the effect of poor retention on mortality in a Brazilian HIV-infected clinical cohort. The analysis included ART-naïve, HIV-infected adults linked to care at the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz between 2000 and 2010, who did not become pregnant nor participate in a clinical trial during the first two years in care (early care). Poor retention in early care was defined as less than 3 out of 4 six-month intervals with a CD4 or HIV-1 RNA laboratory result during early care. Cox proportional hazards models were used to identify factors associated with mortality, and Kaplan-Meier plots were used to describe the survival probability for participants with poor retention versus good retention. Among 1054 participants with a median (interquartile range) follow-up time of 4.2 years (2.6, 6.3), 20% had poor retention in early care and 8% died. Poor retention in early care [adjusted hazard ratio (aHR) 3.09; 95% CI 1.65-5.79], AIDS defining illness (aHR 1.95; 95% CI 1.20-3.18) and lower education (aHR 2.33; 95% CI 1.45-3.75) were associated with increased mortality risk. Our findings highlight the importance of adopting strategies to improve retention in early HIV care.

Mortality in HIV-infected women, heterosexual men, and men who have sex with men in Rio de Janeiro, Brazil: an observational cohort study.

BACKGROUND: Mortality in HIV-infected individuals might differ by sex and mode of HIV acquisition. We aimed to study mortality in HIV-infected women, heterosexual men, and men who have sex with men (MSM) in a cohort from Rio de Janeiro, Brazil. METHODS: In this observational cohort study, we included HIV-infected women, heterosexual men, and MSM (aged ≥18 years) from the Instituto Nacional de Infectologia Evandro Chagas database who were enrolled between Jan 1, 2000, and Oct 30, 2011, and who had at least 60 days of follow-up. Causes of deaths, defined with the Coding of Death in HIV protocol, were documented. Cox proportional hazards models accounting for competing risks were used to explore risk factors for AIDS-related and non-AIDS-related deaths. FINDINGS: We had 10 142 person-years of follow-up from 2224 individuals: 817 (37%) women, 554 (25%) heterosexual men, and 853 (38%) MSM. Of 103 deaths occurred, 64 were AIDS related, 31 were non-AIDS related, and eight were of unknown causes. In unadjusted analyses, compared with women, the hazard of AIDS-related deaths was higher for heterosexual men (hazard ratio [HR] 3·52, 95% CI 1·30-9·08; p=0·009) and for MSM (2·30, 0·89-5·94; p=0·084). After adjustment for age, CD4 cell counts, last HIV viral load, antiretroviral therapy use, and AIDS-defining infection, AIDS-defining malignant disease, and hospital admission during follow-up, the excess risk of AIDS-related death decreased for heterosexual men (adjusted HR 1·99, 0·75-5·25; p=0·163) but was unchanged for MSM (2·24, 0·82-6·11; p=0·114). Non-AIDS-related mortality did not differ by group. INTERPRETATION: Compared with women, increased risk of AIDS-related death in heterosexual men was partly mitigated by risk factors for AIDS mortality, whereas the excess risk in MSM was unchanged. Further study of reasons for disparity in AIDS-related mortality by mode of transmission is needed. FUNDING: US National Institutes of Health, Brazilian National Council of Technological and Scientific Development (CNPq), and Research Funding Agency of the State of Rio de Janeiro (FAPERJ).

Traditional and HIV-specific risk factors for cardiovascular morbidity and mortality among HIV-infected adults in Brazil: a retrospective cohort study.

BACKGROUND: Antiretroviral therapy (ART) agents potentially associated with adverse metabolic profiles are commonly used in low- and middle-income countries. We assessed risk factors for cardiovascular disease (CVD)-related morbidity and mortality in a cohort of HIV-infected, ART-treated adults in Rio de Janeiro, Brazil. METHODS: Hospital records and mortality data between 2000-2010 were examined for incident CVD-related ICD-10 and Coding of Death in HIV diagnoses among adults ≥18 years old on ART, enrolled in an observational cohort. Poisson regression models assessed associations between demographic and clinical characteristics and ART agent or class on CVD event risk. RESULTS: Of 2960 eligible persons, 109 had a CVD event (89 hospitalizations, 20 deaths). Participants were 65 % male, 54 % white, and had median age of 37 and 4.6 years on ART. The median nadir CD4(+) T lymphocyte count was 149 cells/mm(3). The virologic suppression rate at the end of study follow-up was 60 %. In multivariable models, detectable HIV-1 RNA prior to the event, prior CVD, less time on ART, age ≥40 at study baseline, nadir CD4(+) T lymphocyte count ≤50 cells/mm(3), non-white race, male gender, and a history of hypertension were significantly associated with CVD event incidence (p < 0.05), in order of decreasing strength. In multivariate models, cumulative use of tenofovir, zidovudine, efavirenz and ritonavir-boosted atazanavir, darunavir and/or lopinavir were associated with decreased CVD event risk. Recent tenofovir and boosted atazanavir use were associated with decreased risk, while recent stavudine, nevirapine and unboosted nelfinavir and/or indinavir use were associated with increased CVD event risk. CONCLUSIONS: Virologic suppression and preservation of CD4(+) T-lymphocyte counts were as important as traditional CVD risk factor burden in determining incident CVD event risk, emphasizing the overall benefit of ART on CVD risk and the need for metabolically-neutral first- and second-line ART in resource-limited settings.

Diabetes Mellitus is Associated with Increased Death Rates Among HIV-Infected Patients in Rio de Janeiro, Brazil.

Diabetes mellitus (DM) is a major cause of morbidity worldwide and a known factor leading to increased risk of death, especially in conjunction with other risk factors. In this study, we evaluated the prevalence of DM among HIV-infected patients and its association with overall mortality. All HIV-infected patients 18 years or older who were followed in the Instituto Nacional de Infectologia Evandro Chagas (INI) cohort from January 1991 to December 2011 were included. Time-updated covariables included DM status, calendar year, combination antiretroviral therapy (cART), and CD4 cell counts. Fixed demographic covariables included gender and age at entry. Poisson models were used to calculate mortality rate ratios (RR) with robust variances. Among the 4,871 patients included, 1,192 (24.4%) died (mortality rate = 4.72/100 person-years [PY]; 95% confidence interval [CI] = 4.46-5.00). Death rates were significantly higher among those presenting with DM compared with those who did not (6.16/100 vs. 4.61/100 PY, respectively. p = 0.001). In the final model, DM was significantly associated with mortality (RR = 1.74; 95% CI = 1.57-1.94; p < 0.001). When the analysis was restricted to those on cART or the period post-1996, the association between DM and mortality was even stronger (RR = 2.17; 95% CI = 1.91-2.46; p < 0.001 and RR = 1.95; 95% CI = 1.75-2.18; p < 0.001, respectively). Among the major groups of cause of deaths (CODs), the proportion of AIDS-related conditions in patients with DM was lower (74.27% vs. 58.93%, respectively; p < 0.001); whereas in non-AIDS-related conditions, nonimmunodeficiency-related causes (22.44% vs. 34.82%, respectively; p = 0.004) were more common in patients with DM. In conclusion, DM was associated with increased mortality rates even after controlling for HIV-related variables associated to this outcome. Differences in the underlying CODs were identified, reinforcing the necessity to assess and treat comorbidities such as DM in HIV-infected patients.

Predictors of opportunistic illnesses incidence in post combination antiretroviral therapy era in an urban cohort from Rio de Janeiro, Brazil.

BACKGROUND: Opportunistic illnesses still account for a huge proportion of hospitalizations and deaths among HIV-infected patients in the post combination antiretroviral therapy (cART) era, particularly in middle- and low-income countries. The aim of this study was to assess predictors of the top four most incident opportunistic illnesses (tuberculosis, esophageal candidiasis, cerebral toxoplasmosis and Pneumocystis jiroveci pneumonia) in an HIV clinical cohort from a middle-income country in the post cART era. METHODS: A total of 2835 HIV infected participants aged ≥ 18 years at enrollment were followed from January 2000 to December 2012 until the occurrence of their first opportunistic illness, death or end of study, whichever occurred first. Extended Cox proportional hazards regression models, stratified by use of cART, were fitted to assess predictors of opportunistic illness incidence during follow-up. RESULTS: The incidence rates of tuberculosis, esophageal candidiasis, cerebral toxoplasmosis and Pneumocystis jiroveci pneumonia were 15.3, 8.6, 6.0, 4.8 per 1000 persons-year, respectively. Disease specific adjusted Cox models showed that presence of an opportunistic illness at enrollment significantly increased disease incidence while higher nadir CD4+ T lymphocyte count had a significant protective effect in patients not in use of cART. Duration of cART use also significantly reduced disease incidence. CONCLUSIONS: Our findings show that, still in the post-cART era, prevention of opportunistic infections can be achieved by preventing immune deterioration by instituting early use of cART. Interventions focusing on early diagnosis and linkage to care in addition to the prompt initiation of cART are essential to reduce the incidence of opportunistic illnesses among HIV infected patients in post-cART era.

Retention in Early Care at an HIV Outpatient Clinic in Rio de Janeiro, Brazil, 2000-2013.

Retention in early HIV care has been associated with virologic suppression and improved survival, but remains understudied in Brazil. We estimated retention in early HIV care for the period 2000-2013, and identified socio-demographic and clinical factors associated with good retention in an urban cohort from Rio de Janeiro, Brazil. Antiretroviral therapy-naïve, HIV-infected persons ≥18 years old linked to care between 2000 and 2011 were included. Retention in the first 2 years post-linkage (i.e. early care) was defined by the proportion of 6-month intervals with ≥1 HIV laboratory result. "Good" retention was defined as ≥1 HIV laboratory result recorded in at least three intervals. Overall, 80 % of participants met criteria for good retention and retention significantly improved over the study period. Older age, higher education level and early antiretroviral therapy initiation were associated with good retention. Efforts to improve retention in early care in this population should target younger and less-educated HIV-infected persons.

Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study.

BACKGROUND: Access to combination antiretroviral therapy (ART) is expanding in Latin America (Mexico, Central America, and South America) and the Caribbean. We assessed the incidence of and factors associated with regimen failure and regimen change of initial ART in this region. METHODS: This observational cohort study included antiretroviral-naive adults starting ART from 2000 to 2014 at sites in seven countries throughout Latin America and the Caribbean. Primary outcomes were time from ART initiation until virological failure, major regimen modification, and a composite endpoint of the first of virological failure or major regimen modification. Cumulative incidence of the primary outcomes was estimated with death considered a competing event. FINDINGS: 14,027 patients starting ART were followed up for a median of 3.9 years (2.0-6.5): 8374 (60%) men, median age 37 years (IQR 30-44), median CD4 count 156 cells per µL (61-253), median plasma HIV RNA 5.0 log10 copies per mL (4.4-5.4), and 3567 (28%) had clinical AIDS. 1719 (12%) patients had virological failure and 1955 (14%) had a major regimen change. Excluding the site in Haiti, which did not regularly measure HIV RNA, cumulative incidence of virological failure was 7.8% (95% CI 7.2-8.5) 1 year after ART initiation, 19.2% (18.2-20.2) at 3 years, and 25.8% (24.6-27.0) at 5 years; cumulative incidence of major regimen change was 5.9% (5.3-6.4) at 1 year, 12.7% (11.9-13.5) at 3 years, and 18.2% (17.2-19.2) at 5 years. Incidence of major regimen change at the site in Haiti was 10.7% (95% CI 9.7-11.6) at 5 years. Virological failure was associated with younger age (adjusted hazard ratio [HR] 2.03, 95% CI 1.68-2.44, for 20 years vs 40 years), infection through injection drug use (vs infection through heterosexual sex; 1.60, 1.02-2.52), and initiation in earlier calendar years (1.28, 1.13-1.46, for 2002 vs 2006), but was not significantly associated with boosted protease inhibitor-based regimens (vs non-nucleoside reverse transcriptase inhibitor; 1.17, 1.00-1.36). INTERPRETATION: Incidence of virological failure in Latin America and the Caribbean was generally lower than that reported in North America or Europe. Our results suggest the need to design strategies to reduce failure and major regimen change in young patients and those with a history of injection drug use. FUNDING: US National Institutes of Health.

HIV and cancer: a comparative retrospective study of Brazilian and U.S. clinical cohorts.

BACKGROUND: With successful antiretroviral therapy, non-communicable diseases, including malignancies, are increasingly contributing to morbidity and mortality among HIV-infected persons. The epidemiology of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) in HIV-infected populations in Brazil has not been well described. It is not known if cancer trends in HIV-infected populations in Brazil are similar to those of other countries where antiretroviral therapy is also widely available. METHODS: We performed a retrospective analysis of clinical cohorts at Instituto Nacional de Infectologia Evandro Chagas (INI) in Rio de Janeiro and Vanderbilt Comprehensive Care Clinic (VCCC) in Nashville from 1998 to 2010. We used Poisson regression and standardized incidence ratios (SIRs) to examine incidence trends. Clinical and demographic predictors of ADCs and NADCs were examined using Cox proportional hazards models. RESULTS: This study included 2,925 patients at INI and 3,927 patients at VCCC. There were 57 ADCs at INI (65% Kaposi sarcoma), 47 at VCCC (40% Kaposi sarcoma), 45 NADCs at INI, and 82 at VCCC. From 1998 to 2004, incidence of ADCs remained statistically unchanged at both sites. From 2005 to 2010, ADC incidence decreased in both cohorts (INI incidence rate ratio per year = 0.74, p < 0.01; VCCC = 0.75, p < 0.01). Overall Kaposi sarcoma incidence was greater at INI than VCCC (3.0 vs. 1.2 cases per 1,000 person-years, p < 0.01). Incidence of NADCs remained constant throughout the study period (overall INI incidence 3.6 per 1,000 person-years and VCCC incidence 5.3 per 1,000 person-years). Compared to general populations, overall risk of NADCs was increased at both sites (INI SIR = 1.4 [95% CI 1.1-1.9] and VCCC SIR = 1.3 [1.0-1.7]). After non-melanoma skin cancers, the most frequent NADCs were anal cancer at INI (n = 7) and lung cancer at VCCC (n = 11). In multivariate models, risk of ADC was associated with male sex and immunosuppression. Risk of NADC was associated with increased age. CONCLUSIONS: In both cohorts, ADCs have decreased over time, though incidence of KS was higher at INI than VCCC. Rates of NADCs remained constant over time at both sites.