Pathways to Poor Adherence to Antiretroviral Therapy Among People Living with HIV: The Role of Food Insecurity and Alcohol Misuse.

Daily adherence to antiretroviral therapy (ART) increases the length and quality of life of people living with HIV (PLHIV). We explored whether socioeconomic status directly impacts ART adherence and whether part of the effect is mediated by pathways through alcohol misuse or food insecurity. A cross-sectional study was conducted in Rio de Janeiro/Brazil (November/2019 to March/2020) with PLHIV aged ≥ 18 years. Validated instruments were used to measure alcohol use, food insecurity, and ART adherence. Using structural equation modeling we assessed the direct and indirect effects of variables on ART adherence. Participants reported significant challenges: hunger: 12%, alcohol use: 64%, and missing ART doses: 24%. Results showed that lower socioeconomic status increased poor adherence and that this effect was mediated through higher food insecurity. Alcohol misuse also increased poor adherence through a strong direct effect. Providing socio-economic support coupled with interventions to mitigate alcohol's harmful impact can aid HIV care.

RESUMEN: La adherencia diaria a la terapia antirretroviral (TAR) aumenta la duración y calidad de vida de las personas que viven con el VIH (PVVIH). Exploramos si el estatus socioeconómico afecta directamente la adherencia al TAR y si parte del efecto está mediado por vías a través del abuso del alcohol o la inseguridad alimentaria. Se realizó un estudio en Río de Janeiro/Brasil (noviembre/2019 a marzo/2020) con PVVIH con edad ≥ 18 años. Utilizando modelos de ecuaciones estructurales evaluamos los efectos directos e indirectos. Los participantes informaron desafíos significativos: hambre: 12%, consumo de alcohol: 64%, mala adherencia: 24%. Los resultados mostraron que un nivel socioeconómico más bajo aumentaba la mala adherencia por un efecto mediado por mayor inseguridad alimentaria. Abuso de alcohol también aumentó la mala adherencia por un fuerte efecto directo. Brindar apoyo socioeconómico con intervenciones para mitigar el impacto nocivo del alcohol puede ayudar la atención clínica.

Acceptability and usability of oral fluid HCV self-testing for hepatitis C diagnosis: A systematic review and meta-analysis.

Data on the acceptability and usability of hepatitis C virus self-testing (HCVST) remain scarce. We estimated the pooled rates of acceptability/feasibility and re-reading/re-testing agreement of HCVST using oral fluid tests (PROSPERO-CRD42022349874). We searched online databases for studies that evaluated acceptability, usability and inter-reader/operator variability for HCVST using oral fluid tests. Pooled estimates of feasibility, agreement and post-testing perspectives were analysed. Sensitivity analyses were performed in men who have sex with men (MSM) and people who inject drugs (PWID). Heterogeneity was assessed using the I2 statistics. A total of six studies comprising 870 participants were identified: USA (n = 95 with liver disease), Kenya (n = 150 PWID), Egypt (n = 116 from the general population), Vietnam (n = 104 MSM and n = 105 PWID), China (n = 100 MSM) and Georgia (n = 100 MSM and n = 100 PWID)]. All studies used OraQuick® HCV Rapid Antibody Test. The pooled overall estimates for correct sample collection and for people who performed HCVST without needing assistance in any step (95% confidence interval [CI]) were 87.2% [76.0-95.3] (n = 755; I2 = 93.7%) and 62.6% [37.2-84.8] (n = 755; I2 = 98.0%), respectively. The pooled estimate of agreement for re-reading was 95.0% [95% CI 91.5-97.6] (n = 831; I2 = 74.0%) and for re-testing was 94.4% [90.3-97.5] (n = 726; I2 = 77.1%). The pooled estimate of those who would recommend HCVST was 94.4% [84.7-99.6] (n = 625; I2 = 93.7%). Pooled estimates (95% CI) of correct sample collection (72.8% [63.3-81.5] vs. 90.8% [85.9-94.8]) and performance of HCVST without needing assistance (44.1% [14.1-76.7] vs. 78.1% [53.4-95.3]) was lower in PWID compared to MSM. In summary, HCV testing with oral fluid HCVST was feasible and well-accepted. Oral fluid HCVST should be considered in key populations for uptake HCV testing.

The Impact of COVID-19 on HIV Care in Rio de Janeiro, Brazil 2019-2021: Disparities by Age and Gender.

We evaluated COVID-19's impact on HIV care indicators among INI/FIOCRUZ's HIV Clinical Cohort in Rio de Janeiro, Brazil: (1) Adequate care visits: two visits ≥ 90 days apart; (2) Adequate viral load monitoring: ≥ 2 viral load results ≥ 90 days apart; (3) Consistent viral suppression: all viral loads < 40 copies/mL; and (4) ART medication possession ratio (MPR) ≥ 95%. Chi-square tests compared the fraction of participants meeting each indicator per period: pre-pandemic (3/1/2019-2/29/2020) and post-pandemic (3/1/2020-2/28/2021). Logistic regression models were used to assess disparities in adequate care visits. Among 906 participants, care visits and viral load monitoring decreased pre-pandemic to post-pandemic: 77.0-55.1% and 36.6-11.6% (both p < 0.001), respectively. The optimal MPR rate improved from 25.5 to 40.0% (p < 0.001). Post-pandemic period (aOR 0.33, CI 0.28-0.40), transgender women (aOR 0.34, CI 0.22-0.53), and those aged 18-24 years (aOR 0.67, CI 0.45-0.97) had lower odds of adequate care visits. COVID-19 disrupted care access disproportionately for transgender women and younger participants.

Real-world effectiveness of WHO recommended first-line antiretroviral therapies: a cohort study from a middle-income country.

We estimate the effectiveness of antiretroviral therapy (ART) among individuals receiving HIV care in Rio de Janeiro, Brazil. Adults (18y+) initiating ART between Jan/2008 and Dec/2018 (follow-up through Dec/2020) were included. First-line ART (two nucleoside reverse transcriptase inhibitors plus one antiretroviral from another class) was categorized into four categories: non-nucleoside reverse transcriptase inhibitor/NNRTI-based, protease inhibitor/PI-based, integrase strand transfer inhibitor/INSTI-based, and single-tablet regimen (STR, Tenofovir 300mg + Lamivudine 300mg + Efavirenz 600mg). Effectiveness (viral load ≤50 copies/µL) was evaluated at 6(3-9) and 12(9-15) months from ART initiation. Bayesian logistic regression models were used to quantify the association between exposure and outcomes while accounting for missing data. Overall, 1863(57%), 652(19.9%), 412(12.6%), and 342(10.5%) individuals used, respectively, NNRTI-based, PI-based, INSTI-based regimens, and STR. Compared to NNRTIs, the odds of viral suppression with INSTI-based regimens was 76% higher (adjusted OR:1.76, 95%CI:1.23-2.51) at six months but no higher at 12 months. Older age, higher education, CD4 count ≥500 cells/mm3 and viral load <100,000 copies/µL at ART initiation increased the odds of viral suppression. Viral suppression at six months was the strongest predictor of viral suppression at 12 months. These results highlight population groups that could benefit from close monitoring during the first year of ART.

Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil.

BACKGROUND: The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil. METHODS: Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy. RESULTS: A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4-54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2-17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2-52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy. CONCLUSIONS: We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients' therapeutic regimens should be implemented.

Multilevel Analysis of Individual and Neighborhood Characteristics Associated with Viral Suppression Among Adults with HIV in Rio de Janeiro, Brazil.

Understanding the impact of neighborhood context on viral suppression outcomes may help explain health disparities and identify future interventions. We assessed the relationship between individual characteristics, neighborhood socioeconomic context, and viral suppression using multilevel logistic regression models. Adults with HIV initiating antiretroviral therapy (ART) between 2000 and 2017, who resided in Rio de Janeiro and had an HIV-1 RNA level (viral load) measured 90-270 days after ART initiation were included. Overall, 83.9% achieved viral suppression. Participants who were older, had a higher level of education, and identified as heterosexual cisgender men and cisgender men-who-have-sex-with-men had increased odds of viral suppression. Later calendar year of ART initiation carried the strongest association with viral suppression, reflecting the increased effectiveness and tolerability of ART over time. Neighborhood socioeconomic indicators did not predict viral suppression in unadjusted or adjusted analyses, which may result from the integrated care provided in our health care facility together with Brazil's universal treatment.

RESUMEN: Comprender el impacto del contexto representado por el lugar de residencia o vecindario sobre los resultados de supresión viral puede ayudar a explicar las disparidades en salud e identificar futuras intervenciones. Evaluamos la relación entre las características individuales, el contexto socioeconómico del vecindario y la supresión viral utilizando modelos de regresión logística multinivel. Incluimos adultos con VIH que comenzaron terapia antiretroviral (ART) entre los años 2000 y 2017, que residían en Río de Janeiro y tenían un valor de nivel de ARN del VIH-1 (carga viral) medido 90-270 días después del inicio de la ART. En general, el 83.9% logró supresión viral. Los participantes con mayor de edad, mayor nivel de educación, identificados como hombres cisgénero heterosexuales y hombres cisgénero que tienen sexo con hombres tenían mayores probabilidades de supresión viral. Los años calendario más recientes de inicio de ART tuvieron la asociación más fuerte con supresión viral, lo que refleja el incremento de la efectividad y la tolerancia a los antirretrovirales con el paso del tiempo. Los indicadores socioeconómicos del vecindario no predijeron supresión viral en los análisis no ajustados o ajustados, que puede resultar de la atención integrada en nuestro centro de salud junto con el tratamiento universal de Brasil.

Complementary Recruitment Strategies to Reach Men Who Have Sex with Men and Transgender Women: The Experience of a Large Brazilian HIV Prevention Service.

Different strategies have been used to reach men who have sex with men (MSM) and transgender women (TGW) for HIV prevention services. We described the characteristics of MSM and TGW attending a large HIV prevention service in Brazil according to different recruitment strategies or referrals. A total of 2713 individuals (2246[82.8%] MSM and 467[17.2%] TGW) attended the service. Among HIV-negative MSM and TGW, 74.6% and 82.8% were eligible for pre-exposure prophylaxis (PrEP), respectively. PrEP uptake among MSM and TGW was 56.4% and 39.1%, respectively. Participants were mostly referred by peers (43.6%), followed by web-based (24.1%) and venue-based recruitment (16.2%). More young and Black MSM were referred from venue-based recruitment, and web-based strategies more frequently referred MSM with higher education. TGW who were younger and had higher education were more frequently referred from venue-based recruitment. Web-based recruitment failed to reach TGW. Multiple strategies were complementary to reach diverse MSM and TGW populations.

RESUMEN: Diferentes estrategias se han usado para alcanzar hombres que tienen sexo con hombres (HSH) y mujeres trans (MT) en los servicios preventivos del VIH. Describimos las características de HSH y MT que acudieron a un servicio de prevención del VIH en Brasil, de acuerdo con diferentes estrategias de reclutamiento. Un total de 2713 personas (2246[82.8%] HSH y 467[17.2%] MT) asistieron al servicio y aquellos con resultado negativo al VIH (74.6% de HSH y 82.8% de MT) fueron candidatos a la profilaxis preexposición, siendo iniciada por 56.4% y 39.1%, respectivamente. Las referencias al servicio vinieron de pares (43.6%), en línea (24.1%) o por algún sitio (16.2%). Mayoritariamente los HSH jóvenes y negros, y las MT jóvenes con educación superior fueron referidos de algún sitio; mientras que los HSH con educación superior fueron en línea. Este último reclutamiento no sirvió para las MT. Múltiples estrategias fueron complementarias para alcanzar HSH y MT.

Early mortality in a cohort of people living with HIV in Rio de Janeiro, Brazil, 2004-2015: a persisting problem.

BACKGROUND: Global mortality from AIDS-related diseases has been declining since 2005, resulting primarily from the widespread use and early initiation of combination antiretroviral therapy. Despite the significant improvements, high rates of early mortality, usually defined as that occurring within the 1st year of entry to care, have been observed, especially in resource-limited settings. This analysis draws upon data from an observational cohort of people with HIV (PWH) followed at a reference center for HIV/AIDS care and research in the city of Rio de Janeiro, Brazil, to identify the pattern and factors associated with early mortality. METHODS: The study population includes PWH aged 18 or older followed at the National Institute of Infectious Diseases Evandro Chagas who were enrolled between 2004 and 2015. The primary outcome was early mortality, defined as deaths occurring within 1 year of inclusion in the cohort, considering two follow-up periods: 0 to 90 days (very early mortality) and 91 to 365 days (early mortality). Cox proportional hazards models were used to identify the variables associated with the hazard of very early and early mortality. RESULTS: Overall, 3879 participants contributed with 3616.4 person-years of follow-up. Of 220 deaths, 132 happened in the first 90 days and 88 between 91 and 365 days. Very early mortality rate ratios (MRR) show no statistically significant temporal differences between the periods 2004-2006 to 2013-2015. In contrast, for early mortality, a statistically significant decreasing trend was observed: mortality rates in the periods 2004-2006 (MR = 5.5; 95% CI 3.9-7.8) and 2007-2009 (MR = 3.9; 95% CI 2.7-5.7) were approximately four and three-fold higher when compared to 2013-2015 (MR = 1.4; 95% CI 0.7-2.7). Low CD4 count and prior AIDS-defining illness were strongly associated with higher hazard ratios of death, especially when considering very early mortality. CONCLUSIONS: The present study shows an excess of mortality in the 1st year of follow-up with no changes in the mortality rates within 90 days among PWH from Rio de Janeiro. We note the significant impact of initiating treatment with immunosuppression, as evidenced by the increased risk of death among those with low CD4 cell count and with AIDS-defining illnesses.

Safety and Pharmacokinetics of Double-Dose Lopinavir/Ritonavir + Rifampin Versus Lopinavir/Ritonavir + Daily Rifabutin for Treatment of Human Immunodeficiency Virus-Tuberculosis Coinfection.

BACKGROUND: Protease inhibitor-based antiretroviral therapy may be used in resource-limited settings in persons with human immunodeficiency virus and tuberculosis (HIV-TB). Data on safety, pharmacokinetics/pharmacodynamics (PK/PD), and HIV-TB outcomes for lopinavir/ritonavir (LPV/r) used with rifampin (RIF) or rifabutin (RBT) are limited. METHODS: We randomized adults with HIV-TB from July 2013 to February 2016 to arm A, LPV/r 400 mg/100 mg twice daily + RBT 150 mg/day; arm B, LPV/r 800 mg/200 mg twice daily + RIF 600 mg/day; or arm C, LPV/r 400 mg/100 mg twice daily + raltegravir (RAL) 400 mg twice daily + RBT 150 mg/day. All received two nucleoside reverse transcriptase inhibitors and other TB drugs. PK visits occurred on day 12 ± 2. Within-arm HIV-TB outcomes were summarized using proportions and 95% CIs; PK were compared using Wilcoxon tests. RESULTS: Among 71 participants, 52% were women; 72% Black; 46% Hispanic; median age, 37 years; median CD4+ count, 130 cells/mm3; median HIV-1 RNA, 4.6 log10 copies/mL; 46% had confirmed TB. LPV concentrations were similar across arms. Pooled LPV AUC12 (157 203 hours × ng/mL) and Ctrough (9876 ng/mL) were similar to historical controls; RBT AUC24 (7374 hours × ng/mL) and Ctrough (208 ng/mL) were higher, although 3 participants in arm C had RBT Cmax <250 ng/mL. Proportions with week 48 HIV-1 RNA <400 copies/mL were 58%, 67%, and 61%, respectively, in arms A, B, and C. CONCLUSIONS: Double-dose LPV/r+RIF and LPV/r+RBT 150mg/day had acceptable safety, PK and TB outcomes; HIV suppression was suboptimal but unrelated to PK. Faster RBT clearance and low Cmax in 3 participants on RBT+RAL requires further study.

Poor quality of life and incomplete self-reported adherence predict second-line ART virological failure in resource-limited settings.

We evaluated health-related quality of life (QoL) and self-reported incomplete adherence as predictors of early second-line antiretroviral (ART) virological failure (VF). ACTG A5273 study participants completed the ACTG SF-21 measure which has 8 QoL domains. We used exact logistic regression to assess the association of QoL at baseline and week 4 with early VF adjusted for self-reported adherence. Of 500 individuals (51% women, median age 39 years) in this analysis, 79% and 75% self-reported complete adherence (no missing doses in the past month) at weeks 4 and 24, respectively. Early VF was experienced by 7% and more common among those who self-reported incomplete adherence. Participants with low week 4 QoL scores had higher rates of early VF than participants with high scores. After adjusting for self-reported adherence at week 4, VL and CD4 at baseline, cognitive functioning, pain and mental health domains were significantly associated with subsequent early VF. In this post-hoc analysis, poorer QoL adds to self-reported incomplete adherence after 4 weeks of second-line ART in predicting VF at week 24. Evaluation is needed to assess whether individuals with poorer QoL might be targeted for greater support to reduce risk of VF.Trial registration: ClinicalTrials.gov identifier: NCT01352715.

Effectiveness of generic direct-acting agents for the treatment of hepatitis C: systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of generic direct-acting agents and brand-name medicines for treating hepatitis C virus (HCV) infection by conducting a systematic review and meta-analysis. METHODS: We searched online databases for studies that reported sustained virological responses 12 weeks after the end of HCV treatment with generic direct-acting agents. We derived pooled proportions of treated patients with a sustained virological response from intention-to-treat and per-protocol analyses. In addition, we calculated the pooled relative risk (RR) of a sustained virological response brand-name versus generic direct-acting agents using a random-effects model (DerSimonian-Laird) from the data available. Between-study heterogeneity was assessed using the I2 statistic. FINDINGS: We identified 19 studies involving a total of 57 433 individuals from eight territories or regions. The pooled overall proportions of patients with a sustained virological response were 98% (95% confidence interval, CI: 97-99; 18 studies; I2 = 94.1%) in per-protocol analyses and 96% (95% CI: 93-98; 8 studies; I2 = 68.1%) in intention-to-treat analyses. The likelihood of a sustained virological response with brand-name medicines was similar to that with generic direct-acting agents (RR: 1.00; 95% CI: 0.98-1.02; I2 = 0.0%). The likelihood of a sustained virological response was significantly higher in patients without than with cirrhosis (RR:1.03; 95% CI: 1.01-1.06; 7 studies) but was not significantly affected by either previous treatment (3 studies) or human immunodeficiency virus coinfection (3 studies). CONCLUSION: Generic direct-acting agents are highly effective for treating hepatitis C. Generic agents should be considered in resource-constrained settings for decreasing the burden of liver disease in HCV-infected patients.

Effectiveness of direct-acting agents for hepatitis C and liver stiffness changing after sustained virological response.

BACKGROUND AND AIM: Few studies have evaluated sustained virological response (SVR) rates by direct-acting agents (DAAs) and liver stiffness measurement (LSM) changing post-SVR in limited-resource settings. We aimed to describe the effectiveness of DAAs for hepatitis C virus treatment and to assess the changing of LSM post-SVR. METHODS: This retrospective study analyzed data of consecutive hepatitis C virus-infected patients treated by DAAs from 2015 to 2017 in two tertiary centers in Brazil. SVR rates were reported by intention-to-treat and per-protocol analyses. LSM by transient elastography performed before treatment and post-SVR was compared, and logistic regression models were performed. RESULTS: Six hundred seventy-one patients (63% female, 62 years [55-68], 89% genotype 1, 8% HIV co-infected, and 64% with cirrhosis) were included. Most patients were treated by sofosbuvir/daclatasvir ± ribavirin (74%) and sofosbuvir/simeprevir ± ribavirin (21%). SVR rates (95% confidence interval [CI]) were 94.6% (92.7-96.1) and 97.8% (96.4-98.7) for intention-to-treat and per-protocol analyses, respectively. The leading adverse event was anemia (9.6% [95% CI 7.6-12.1]). Pretreatment and post-SVR12 LSM were available in 400 patients. LSM had significantly decreased after SVR (13.6 kPa [interquartile range, 10.0-21.6] vs 10.2 kPa [7.0-17.6], P < 0.001). A total of 167 patients (42%) decreased at least 30% of LSM post-SVR. The absence of type 2 diabetes (odds ratio = 1.52 [95% CI 1.05-2.21], P = 0.028) and presence of platelet count ≥ 150 × 109 /mm3 (odds ratio = 1.75 [1.23-2.50], P = 0.002) were independently associated with a significant LSM regression (≥ 30%) post-SVR. CONCLUSION: DAAs were highly effective and safe, and LSM significantly decreased after SVR in a real-life cohort in Brazil. The absence of type 2 diabetes and presence of high platelet count were independently associated with LSM decrease post-SVR.

Health-related quality of life assessment among people living with HIV in Rio de Janeiro, Brazil: a cross-sectional study.

PURPOSE: To assess health-related quality of life (HRQoL) and its associated factors among people living with HIV/AIDS (PLWHA) in Rio de Janeiro, Brazil. METHODS: A cross-sectional study including PLWHA receiving usual HIV-care at Instituto Nacional de Infectologia Evandro Chagas (INI/Fiocruz) was conducted between 2014 and 2016 in Rio de Janeiro, Brazil. The EQ-5D-3L assessed HRQoL; PHQ-2 and ASSIST were used for screening depression and substance use, respectively. Clinical variables were obtained from the INI/Fiocruz cohort database, and structured questions evaluated intimate partner violence, sexual abstinence and relationship status. Data were analysed using multivariable Tobit regression model. RESULTS: A total of 1480 PLWHA were included: 64.7% were male at birth (38.4% men who have sex with men [MSM], 24.3% heterosexual men and 2% transgender women [TGW]); median age was 43.1 years, and 95.8% were receiving antiretroviral therapy. The median EQ-5D-3L utility score was 0.801. Results showed that the following factors: MSM and women; older age; lower educational level; no engagement in a relationship; depression screening positive; polysubstance use; and, detectable viral load were independently associated with worse HRQoL. CONCLUSIONS: PLWHA under care at INI/Fiocruz presented good HRQoL. Polysubstance use, depression and lower educational level were among the factors negatively associated with HRQoL. This was the first time that the EQ-5D-3L utility scores were calculated for a considerable number of PLWHA in Brazil, which is a fundamental piece of information for future cost-effectiveness analysis.

Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study.

BACKGROUND: Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). METHODS: Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). RESULTS: In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17-1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26-0.87). CONCLUSION: Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.

Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors.

Background: Obesity rates are increasing among HIV-infected individuals, but risk factors for obesity development on ART remain unclear. Objectives: In a cohort of HIV-infected adults in Rio de Janeiro, Brazil, we aimed to determine obesity rates before and after ART initiation and to analyse risk factors for obesity on ART. Methods: We retrospectively analysed data from individuals initiating ART between 2000 and 2015. BMI was calculated at baseline (time of ART initiation). Participants who were non-obese at baseline and had ≥90 days of ART exposure were followed until the development of obesity or the end of follow-up. Obesity incidence rates were estimated using Poisson regression models and risk factors were assessed using Cox regression models. Results: Of participants analysed at baseline (n = 1794), 61.3% were male, 48.3% were white and 7.9% were obese. Among participants followed longitudinally (n = 1567), 66.2% primarily used an NNRTI, 32.9% a PI and 0.9% an integrase strand transfer inhibitor (INSTI); 18.3% developed obesity and obesity incidence was 37.4 per 1000 person-years. In multivariable analysis, the greatest risk factor for developing obesity was the use of an INSTI as the primary ART core drug (adjusted HR 7.12, P < 0.0001); other risk factors included younger age, female sex, higher baseline BMI, lower baseline CD4+ T lymphocyte count, higher baseline HIV-1 RNA, hypertension and diabetes mellitus. Conclusions: Obesity following ART initiation is frequent among HIV-infected adults. Key risk factors include female sex, HIV disease severity and INSTI use. Further research regarding the association between INSTIs and the development of obesity is needed.

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.

Age-standardized mortality rates related to viral hepatitis in Brazil.

BACKGROUND: Liver-related mortality has been increasing worldwide. We aimed to estimate the age-standardized mortality rates from viral hepatitis in Brazil. METHODS: The Brazilian National Death Registry was analyzed from 2008 to 2014. Viral hepatitis deaths were defined by the following ICD-10 codes in the death certificate: hepatitis A [B15.0; B15.9]; hepatitis B [B16.2; B16.9; B18.1]; hepatitis C [B17.1; B18.2]; hepatitis Delta [B16.0; B16.1; B18.0; B17.0] and other viral hepatitis [B17.2; B17.8; B18.8; B18.9; B19.0; B19.9]. Crude mortality rates were calculated by the ratio between total number of deaths and estimated population. Mortality rates were age-standardized by the direct method using the WHO standard population. RESULTS: Thirty four thousand ,nine hundred seventy eight deaths had viral hepatitis mentioned in their death certificate [65% male, aged 58 years, 73% associated with hepatitis C]. Age-standardized mortality rate (95% CI) due to viral hepatitis was 2.695 (2.667-2.724) deaths per 100,000 inhabitants: South region had the higher rates [3.997 (3.911-4.085)]. Mortality rates associated with hepatitis A and Delta were 0.032 (0.029-0.035) and 0.028 (0.025-0.031), respectively. Hepatitis C mortality rates were 4-fold higher than those associated with hepatitis B [1.964 (1.940-1.989) vs 0.500 (0.488-0.512)]. South region had the higher rates for hepatitis C [3.163 (3.087-3.241)] and North had the higher rates for hepatitis A [0.066 (0.049-0.087)], B [0.986 (0.918-1.058)] and Delta [0.220 (0.190-0.253)]. CONCLUSION: Viral hepatitis remains a major public health issue in Brazil. Mortality rates were not homogeneous across the country, suggesting that health policies should be customized according to geographical location.

Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

A case-cohort analysis of human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ≥ 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 205 individuals (24%). A persistently elevated CRP level but not an elevated CRP level only at a single time point was independently associated with increased clinical failure, compared with a persistently low CRP level, despite achievement of virologic suppression. Serial monitoring of CRP levels could identify individuals who are at highest risk of HIV progression and may benefit from future adjunct antiinflammatory therapies.