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Browsing by Author "Shepherd, Bryan E"

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A Comparison of Seven Cox Regression-Based Models to Account for Heterogeneity Across Multiple HIV Treatment Cohorts in Latin America and the Caribbean
(2015-5) Giganti, Mark J.; Luz, Paula M.; Caro-Vega, Yanink; Cesar, Carina; Padgett, Denis; Koenig, Serena; Echevarria, Juan; McGowan, Catherine C; Shepherd, Bryan E
Many studies of HIV/AIDS aggregate data from multiple cohorts to improve power and generalizability. There are several analysis approaches to account for cross-cohort heterogeneity; we assessed how different approaches can impact results from an HIV/AIDS study investigating predictors of mortality. Using data from 13,658 HIV-infected patients starting antiretroviral therapy from seven Latin American and Caribbean cohorts, we illustrate the assumptions of seven readily implementable approaches to account for across cohort heterogeneity with Cox proportional hazards models, and we compare hazard ratio estimates across approaches. As a sensitivity analysis, we modify cohort membership to generate specific heterogeneity conditions. Hazard ratio estimates varied slightly between the seven analysis approaches, but differences were not clinically meaningful. Adjusted hazard ratio estimates for the association between AIDS at treatment initiation and death varied from 2.00 to 2.20 across approaches that accounted for heterogeneity; the adjusted hazard ratio was estimated as 1.73 in analyses that ignored across cohort heterogeneity. In sensitivity analyses with more extreme heterogeneity, we noted a slightly greater distinction between approaches. Despite substantial heterogeneity between cohorts, the impact of the specific approach to account for heterogeneity was minimal in our case study. Our results suggest that it is important to account for across cohort heterogeneity in analyses, but that the specific technique for addressing heterogeneity may be less important. Because of their flexibility in accounting for cohort heterogeneity, we prefer stratification or meta-analysis methods, but we encourage investigators to consider their specific study conditions and objectives.
Antiretroviral therapy and Kaposi’s sarcoma trends and outcomes among adults with HIV in Latin America
(2021-01-06) Castilho, Jessica L; Kim, Ahra; Jenkins, Cathy a; Grinsztejn, Beatriz; Gotuzzo, Eduardo; Fink, Valeria; Padgett, Denis; Belaunzaran-Zamudio, Pablo F; Crabtree-Ramírez, Brenda; Escuder, Maria Mercedes; Souza, Rosa Alencar; Tenore, Simone B; Pimentel, Sidnei R; Rodrigues Ikeda, Maria Letícia; de Alencastro, Paulo R; Tupinanbas, Unai; Brites, Carlos; Luz, Estela; Netto, Juliana; Cortes, Claudia; Grangeiro, Alexandre; Shepherd, Bryan E; McGowan, Catherine C; The Caribbean, Central, South America network for HIV Epidemiology (CCASAnet)
Abstract Introduction Kaposi’s sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART). Methods Cohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression. Results Of 25 981 PWH, 481 had incident KS, including 200 ART-naïve and 281 ART-treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person-years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male-to-male sex, KS risk after ART was associated with age and history of other AIDS-defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation. Conclusions KS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.
Assessing the HIV Care Continuum in Latin America: progress in clinical retention, cART use and viral suppression
(2016-04-08) Rebeiro, Peter F; Cesar, Carina; Shepherd, Bryan E; De Boni, Raquel B; Cortes, Claudia; Rodriguez, Fernanda; Belaunzarán-Zamudio, Pablo; Pape, Jean W; Padgett, Denis; Hoces, Daniel; McGowan, Catherine C; Cahn, Pedro
Introduction We assessed trends in HIV Care Continuum outcomes associated with delayed disease progression and reduced transmission within a large Latin American cohort over a decade: clinical retention, combination antiretroviral therapy (cART) use and viral suppression (VS). Methods Adults from Caribbean, Central and South America network for HIV epidemiology clinical cohorts in seven countries contributed data between 2003 and 2012. Retention was defined as two or more HIV care visits annually, >90 days apart. cART was defined as prescription of three or more antiretroviral agents annually. VS was defined as HIV-1 RNA <200 copies/mL at last measurement annually. cART and VS denominators were subjects with at least one visit annually. Multivariable modified Poisson regression was used to assess temporal trends and examine associations between age, sex, HIV transmission mode, cohort, calendar year and time in care. Results Among 18,799 individuals in retention analyses, 14,380 in cART analyses and 13,330 in VS analyses, differences existed between those meeting indicator definitions versus those not by most characteristics. Retention, cART and VS significantly improved from 2003 to 2012 (63 to 77%, 74 to 91% and 53 to 82%, respectively; p<0.05, each). Female sex (risk ratio (RR)=0.97 vs. males) and injection drug use as HIV transmission mode (RR=0.83 vs. male sexual contact with males (MSM)) were significantly associated with lower retention, but unrelated with cART or VS. MSM (RR=0.96) significantly decreased the probability of cART compared with heterosexual transmission. Conclusions HIV Care Continuum outcomes improved over time in Latin America, though disparities for vulnerable groups remain. Efforts must be made to increase retention, cART and VS, while engaging in additional research to sustain progress in these settings.
Early Retention in Care Neither Mediates Nor Modifies the Effect of Sex and Sexual Mode of HIV Acquisition on HIV Survival in the Americas
(https://doi.org/10.1089/apc.2018.0028, 2018-08-01) Coelho, Lara; Rebeiro, Peter F; Castilho, Jessica L; Caro-Vega, Yanink; Mejia, Fernando A; Cesar, Carina; Cortes, Claudia; Padgett, Denis; McGowan, Catherine C; Veloso, Valdiléa G; Sterling, Timothy R; Grinsztejn, Beatriz; Shepherd, Bryan E; Luz, Paula M; for the CCASAnet
Early retention in care, sex, and sexual mode of HIV acquisition has been associated with mortality risk among persons living with HIV (PLWH). We assessed whether early retention in care mediates or modifies the association between mortality and sex and sexual mode of HIV acquisition among PLWH on antiretroviral therapy (ART) in the Americas. ART-naïve, adult PLWH (≥18 years) enrolling at Caribbean, Central and South America network for HIV epidemiology (CCASAnet) and Vanderbilt Comprehensive Care Clinic sites 2000–2015, starting ART, and with ≥1 visit after ART-start were included. Early retention in care was defined as ≥2 HIV care visits/labs ≥90 days apart in the first year of ART. Cox models assessed the association between early retention in care, sex, and sexual mode of HIV acquisition [i.e., women, heterosexual men and men who have sex with men (MSM)], and mortality. Associations were estimated separately by site and pooled. Among 11,721 included PLWH (median follow-up, 4.3 years; interquartile range, 2.0–7.6), 647 died (rate = 10.9/1000 person-years) and 1985 were lost to follow-up (rate = 33.6/1000 person-years). After adjustment for confounders, early retention in care was associated with lower mortality during subsequent years (pooled hazard ratio = 0.47; 95% confidence interval = 0.39–0.57). MSM had lower and heterosexual men had comparable mortality risk to women; risks were similar when adjusting for early retention in care. Additionally, no evidence of an interaction between early retention in care and sex and sexual mode of HIV acquisition on mortality was observed (p > 0.05). Early retention in care substantially reduced mortality but does not mediate or modify the association between sex and sexual mode of HIV acquisition and mortality in our population.
Frequency of non-communicable diseases in people 50 years of age and older receiving HIV care in Latin America
(2020-06-17) Belaunzaran-Zamudio, Pablo F; Caro-Vega, Yanink; Giganti, Mark J; Castilho, Jessica L; Crabtree-Ramirez, Brenda E; Shepherd, Bryan E; Mejía, Fernando; Cesar, Carina; Moreira, Rodrigo C; Wolff, Marcelo; Pape, Jean W; Padgett, Denis; McGowan, Catherine C; Sierra-Madero, Juan G; for the Caribbean, Central and South American network for HIV epidemiology (CCASAnet)
Background A growing population of older adults with HIV will increase demands on HIV-related healthcare. Nearly a quarter of people receiving care for HIV in Latin America are currently 50 years or older, yet little is known about the frequency of comorbidities in this population. We estimated the prevalence and incidence of non-communicable diseases (NCDs) among people 50 years of age or older (≥50yo) receiving HIV care during 2000–2015 in six centers affiliated with the Caribbean, Central and South American network for HIV epidemiology (CCASAnet). Methods We estimated the annual prevalence, and overall prevalence and incidence of cardiovascular diseases, diabetes, hypertension, dyslipidemia, psychiatric disorders, chronic liver and renal diseases, and non-AIDS-defining cancers, and multimorbidity (more than one NCD) of people ≥50yo receiving care for HIV. Analyses were performed according to age at enrollment into HIV care (<50yo and ≥50yo). Results We included 3,415 patients ≥50yo, of whom 1,487(43%) were enrolled at age ≥50 years. The annual prevalence of NCDs increased from 32% to 68% and multimorbidity from 30% to 40% during 2000–2015. At the last registered visit, 53% of patients enrolled <50yo and 50% of those enrolled ≥50yo had at least one NCD. Most common NCDs at the last visit in each age-group at enrollment were dyslipidemia (36% in <50yo and 28% in ≥50yo), hypertension (17% and 18%), psychiatric disorders (15% and 10%), and diabetes (11% and 12%). Conclusions The prevalence of NCDs and multimorbidity in people ≥50 years receiving care for HIV in CCASAnet centers in Latin America increased substantially in the last 15 years. Our results make evident the need of planning for provision of complex, primary care for aging adults living with HIV.
Late-onset opportunistic infections while receiving anti-retroviral therapy in Latin America: burden and risk factors
(International Society for Infectious Diseases, 2022-09) Núñez, Isaac; Crabtree-Ramirez, Brenda; Shepherd, Bryan E; Sterling, Timothy R; Cahn, Pedro; Veloso, Valdiléa G; Cortes, Claudia; Padgett, Denis; Gotuzzo, Eduardo; Sierra-Madero, Juan; McGowan, Catherine C; Person, Anna K; Caro-Vega, Yanink
Objectives: The aim of this study was to describe the incidence, clinical characteristics, and risk factors of late-onset opportunistic infections (LOI) in people who live with HIV (PWLHA) within the Caribbean, Central and South America network for HIV epidemiology. Methods: We performed a retrospective cohort study including treatment-naive PWLHA enrolled at seven sites (Argentina, Brazil, Chile, Peru, Mexico, and two sites in Honduras). Follow-up began at 6 months after treatment started. Outcomes were LOI, loss to follow-up, and death. We used a Cox proportional hazards model and a competing risks model to evaluate risk factors. Results: A total of 10,583 patients were included. Median follow up was at 5.4 years. LOI occurred in 895 (8.4%) patients. Median time to opportunistic infection was 2.1 years. The most common infections were tuberculosis (39%), esophageal candidiasis (10%), and Pneumocystis jirovecii (P. jirovecii) pneumonia (10%). Death occurred in 576 (5.4%) patients, and 3021 (28.5%) patients were lost to follow-up. A protease inhibitor-based regimen (hazard ratio 1.25), AIDS-defining events during the first 6 months of antiretroviral-treatment (hazard ratio 2.12), starting antiretroviral-treatment in earlier years (hazard ratio 1.52 for 2005 vs 2010), and treatment switch (hazard ratio 1.31) were associated with a higher risk of LOI. Conclusion: LOI occurred in nearly one in 10 patients. People with risk factors could benefit from closer follow-up.
Monitoring of HIV treatment in seven countries in the WHO Region of the Americas
(2015-8) Belaunzarán-Zamudio, Pablo; Caro-Vega, Yanink; Shepherd, Bryan E; Crabtree-Ramirez, Brenda; Luz, Paula; Grinsztejn, Beatriz; Cesar, Carina; Cahn, Pedro; Cortes, Claudia; Wolff, Marcelo; Pape, Jean W; Padgett, Denis; Gotuzzo, Eduardo; McGowan, Catherine; Sierra Madero, Juan; CCASAnet
Objective: To determine the prevalence of adequate monitoring and the costs of measuring CD4+ T-lymphocytes (CD4+ cell) and human immunodeficiency virus (HIV) viral load in people receiving antiretroviral therapy (ART) in seven countries in the WHO Region of the Americas. Methods: We obtained retrospective, longitudinal data for 14 476 adults who started a first ART regimen at seven HIV clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru between 2000 and 2011. We estimated the proportion of 180-day periods with adequate monitoring, which we defined as at least one CD4+ cell count and one viral load measurement. Factors associated with adequate monitoring were analysed using regression methods. The costs of the tests were estimated. Findings: The median follow-up time was 50.4 months; the proportion of 180-day periods with adequate CD4+ cell counts was 69% while the proportion with adequate monitoring was 62%. Adequate monitoring was more likely in participants who were older, who started ART more recently, whose first regimen included a non-nucleoside reverse transcriptase inhibitor or who had a CD4+ cell count less than 200 cells/µl at ART initiation. The cost of one CD4+ cell count ranged from 7.37 United States dollars (US$) in Argentina to US$ 64.09 in Chile; the cost of one viral load measurement ranged from US$ 20.34 in Brazil to US$ 186.28 in Haiti. Conclusion: In HIV-infected participants receiving ART in the WHO Region of the Americas, CD4+ cell count and viral load monitoring was often carried out less frequently than regional guidelines recommend. The laboratory costs of monitoring varied greatly.
Substance use and adherence among people living with HIV/ AIDS receiving cART in Latin America
(2016-04) De Boni, Raquel B; Shepherd, Bryan E; Grinsztejn, Beatriz; Cesar, Carina; Cortes, Claudia; Padgett, Denis; Gotuzzo, Eduardo; Belaunzarán-Zamudio, Pablo; Rebeiro, Peter F; Duda, Stephany N; McGowan, Catherine C
This cross-sectional study describes substance use prevalence and its association with combination antiretroviral therapy (cART) adherence among 3343 individuals receiving care at HIV clinics in Argentina, Brazil, Chile, Honduras, Mexico, and Peru. A rapid screening tool evaluated self-reported 7-day recall of alcohol, marijuana, cocaine, heroin, and methamphetamine use, and missed cART doses. Overall, 29.3 % individuals reported having ≥1 alcoholic drinks, 5.0 % reported any illicit drug use and 17.0 % reported missed cART doses. In the logistic regression model, compared to no substance use, alcohol use [adjusted odds ratio (AOR) = 2.46, 95 % confidence interval (CI): 1.99–3.05], illicit drug use (AOR = 3.57, 95 % CI: 2.02–6.30), and using both alcohol and illicit drugs (AOR = 4.98, 95 % CI: 3.19–7.79) were associated with missed cART doses. The associations between substance use and likelihood of missing cART doses point to the need of targeting alcohol and illicit drug use to improve adherence among people living with HIV in Latin America
Survival after cancer diagnosis in a cohort of HIV-positive individuals in Latin America
(2018-05-08) Fink, Valeria; Jenkins, Cathy A; Castilho, Jessica L; Person, Anna K; Shepherd, Bryan E; Grinsztejn, Beatriz; Netto, Juliana; Crabtree-Ramirez, Brenda; Cortes, Claudia; Padgett, Denis; Jayathilake, Karu; McGowan, Catherine; Cahn, Pedro
Background This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. Methods Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC). The association of mortality with cancer- and HIV-related factors was assessed using Kaplan-Meier curves and Cox proportional hazards models stratified by clinic site and cancer type. Results Among 15,869 patients, 783 had an eligible cancer diagnosis; 82% were male and median age at cancer diagnosis was 39 years (interquartile range [IQR]: 32–47). Patients were from Brazil (36.5%), Argentina (19.9%), Chile (19.7%), Mexico (19.3%), and Honduras (4.6%). A total of 564 ADC and 219 NADC were diagnosed. Patients with NADC had similar survival probabilities as those with ADC at one year (81% vs. 79%) but lower survival at five years (60% vs. 69%). In the adjusted analysis, risk of mortality increased with detectable viral load (adjusted hazard ratio [aHR] = 1.63, p = 0.02), age (aHR = 1.02 per year, p = 0.002) and time between HIV and cancer diagnoses (aHR = 1.03 per year, p = 0.01). Conclusion ADC remain the most frequent cancers in the region. Overall mortality was related to detectable viral load and age. Longer-term survival was lower after diagnosis of NADC than for ADC, which may be due to factors unrelated to HIV.
Temporal Trends in Age at HIV Diagnosis in Cohorts in the United States, the Caribbean, and Central and South America
(2015-9) Crabtree-Ramirez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E; Turner, Megan; Carriquiry, Gabriela; Fink, Valeria; Luz, Paula M.; Cortes, Claudia; Rouzier, Vanessa; Padgett, Denis; Jayathilake, Karu; McGowan, Catherine C; Person, Anna K.
In the United States (USA), the age of those newly diagnosed with HIV is changing, particularly among men who have sex with men (MSM). A retrospective analysis included HIV-infected adults from seven sites in the Caribbean, Central and South America network (CCASAnet) and the Vanderbilt Comprehensive Care Clinic (VCCC-Nashville, Tennessee, USA). We estimated the proportion of patients <25 years at HIV diagnosis by calendar year among the general population and MSM. 19,466 (CCASAnet) and 3,746 (VCCC) patients were included. The proportion <25 years at diagnosis in VCCC increased over time for both the general population and MSM (p < 0.001). Only in the Chilean site for the general population and the Brazilian site for MSM were similar trends seen. Subjects <25 years of age at diagnosis were less likely to be immunocompromised at enrollment at both the VCCC and CCASAnet. Recent trends in the USA of greater numbers of newly diagnosed young patients were not consistently observed in Latin America and the Caribbean. Prevention efforts tailored to young adults should be increased.
Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America
(2016-06-07) Crabtree-Ramírez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E; Grinsztejn, Beatriz; Wolff, Marcelo; Cortes, Claudia; Padgett, Denis; Carriquiry, Gabriela; Fink, Valeria; Jayathilake, Karu; Person, Anna K; McGowan, Catherine; Sierra-Madero, Juan; Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet), of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Program
Background Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in “real life” settings in Latin America has not been evaluated. Methods Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) ≥18 years of age at enrolment, from 2001–2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. Results A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8–12.1) weeks before 2009 to 4.3 (IQR 2.0–7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). Discussion The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the publication of evidence of its benefit. We found important heterogeneity between sites which may reflect differences in clinical practices, local guidelines, and access to HAART. The impact of the timing of HAART initiation after OI on patient survival in this “real life” context needs further evaluation.

Browsing by Author "Shepherd, Bryan E"

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