Browsing by Author "McGowan, Catherine C"

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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.
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    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.
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    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.
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    Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network
    (2016-01-01) Wolff, Marcelo; Shepherd, Bryan; Cortes, Claudia; Rebeiro, Peter; Cesar, Carina; Wagner Cardoso, Sandra; Pape, Jean W; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C
    Background: HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications. Methods: HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2. Results: Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8). Conclusions: Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.
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    Cohort Profile: Caribbean, Central and South America Network for HIV research (CCASAnet) collaboration within the International Epidemiologic Databases to Evaluate AIDS (IeDEA) programme
    (2007-09-10) McGowan, Catherine C; Cahn, Pedro; Gotuzzo, Eduardo; Padgett, Denis; Pape, Jean W; Wolff, Marcelo; Schechter, Mauro; Masys, Daniel R
    How did the study come about? The HIV/AIDS epidemic has evolved in its third decade to be an unprecedented human catastrophe of global scale and importance. Although an historic response for change and intervention has led to decreased rates of new infections and HIV-associated mortality in many communities, the enormity of the pandemic continues to overwhelm already constrained resources everywhere. Improved understanding of antiretroviral therapy (ART) responses and viral and host characteristics, both within and between diverse settings and populations, is needed to guide initiatives in HIV prevention and treatment worldwide.
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    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.
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    Estimated life expectancy gains with antiretroviral therapy among adults with HIV in Latin America and the Caribbean: a multisite retrospective cohort study
    (2021-05) Smiley, Casey L; Rebeiro, Peter F; Cesar, Carina; Belaunzaran-Zamudio, Pablo F; Crabtree-Ramirez, Brenda; Padgett, Denis; Gotuzzo, Eduardo; Cortes, Claudia; Pape, Jean; Veloso, Valdiléa G; McGowan, Catherine C; Jessica L, Castilho; Caribbean, Central and South America network for HIV epidemiology (CCASAnet)
    Background There are few data on life expectancy gains among people living with HIV in low-income and middle-income settings where antiretroviral therapy (ART) is increasingly available. We aimed to analyse life expectancy trends from 2003 to 2017 among people with HIV beginning treatment with ART within the Caribbean, central America, and South America. Methods We did a multisite retrospective cohort study and included people with HIV who had started treatment with ART and were aged 16 years or older between Jan 1, 2003, and Dec 31, 2017, from Caribbean, Central and South America network for HIV epidemiology (CCASAnet) sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru, who contributed person-time data from the age of 20 years until date of death, last contact, database closure, or Dec 31, 2017. We used the Chiang method of abridged life tables to estimate life expectancy at age 20 years for three eras (2003–08, 2009–12, and 2013–17) overall and by demographic and clinical characteristics at ART initiation. We used Poisson regression models to weight mortality rates to account for informative censoring. Findings 30 688 people with HIV were included in the study; 17 491 (57·0%) were from the Haiti site and 13 197 (43·0%) were from all other sites. There were 2637 deaths during the study period: 1470 in Haiti and 1167 in other sites. Crude and weighted mortality rates decreased among all age groups over calendar eras. From 2003–08 to 2013–17, overall life expectancy for people with HIV at age 20 years increased from 13·9 years (95% CI 12·5–15·2) to 61·2 years (59·0–63·4) in Haiti and from 31·0 years (29·3–32·8) to 69·5 years (67·2–71·8) in other sites. Life expectancies at the end of the study period were within 10 years of those of the general population (69·9 years in Haiti and 78·0 years in all other sites in 2018). Disparities in life expectancy among people with HIV by sex or HIV transmission risk factor, CD4 cell count, level of education, and history of tuberculosis at or before ART initiation persisted across calendar eras. Interpretation Life expectancy among people with HIV receiving ART has significantly improved in Latin America and the Caribbean. Persistent disparities in life expectancy among people with HIV by demographic and clinical factors at ART initiation highlight vulnerable populations in the region. Funding National Institutes of Health. Translation For the Spanish translation of the abstract see Supplementary Materials section.
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    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.
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    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.
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    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
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    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.