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Browsing by Author "Crabtree-Ramirez, Brenda"

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Cancer in HIV-Infected Persons From the Caribbean, Central and South America
(2011) Fink, Valeria; Shepherd, Bryan E.; Cesar, Carina; Krolewiecki, Alejandro J.; Wehbe, Francisco; Cortes, Claudia; Crabtree-Ramirez, Brenda; Padgett, Denis; Shafaee, Mehdi; Schechter, Mauro; Gotuzzo, Eduardo; Bacon, Melanie; McGowan, Catherine C.; Cahn, Pedro; Masys, Daniel R.; Caribbean Central South America Network for HIV Research Collaboration of the International Epidemiologic Databases to Evaluate AIDS Program
Background: HIV-infected individuals have heightened cancer risk. With the advent of highly active antiretroviral therapy (HAART), the frequency of some AIDS-defining cancers (ADC) has decreased although certain non-AIDS-defining cancers (NADC) are becoming more frequent. Cancers among HIV-infected individuals in Latin American and the Caribbean have not yet been carefully studied. Methods: Cancer cases among the Caribbean, Central and South American network for HIV Research (CCASAnet) cohort were identified reviewing clinical records and pre-existing databases. Results: There were 406 cancers reported: 331 ADC (224 Kaposi sarcomas and 98 non Hodgkin lymphomas). Most frequent NADC (n = 75) were Hodgkin lymphoma and skin cancers. Seventy-three percent of NADC and 45% of ADC were diagnosed >1 year after HIV diagnosis. Fifty-six percent of ADC occurred before HAART start. Median time from HAART start until cancer diagnosis was 2.5 years for NADC and 0.5 years for ADC (P = <0.001). Within 3372 HAART starters, 158 were diagnosed with 165 cancers (82.4% ADC); 85 cases were previous to or concomitant with HAART initiation. Incidence of cancer after HAART initiation in 8080 person-years of follow-up was 7.2 per 1000 person-years (95% confidence interval = 5.5 to 9.3) for ADC and 2.7 (95% confidence interval = 1.8 to 4.1) for NADC; incidence was higher in the first 2 months, particularly for ADC (47.6). A pre-HAART ADC was a predictor of mortality after adjusting for age, sex, and CD4 at HAART initiation. Conclusions: ADC were the most frequent cancers in this region and were often diagnosed close to HIV diagnosis and HAART start. Incidence of cancer was highest around HAART initiation.
Cross-Sectional Analysis of Late HAART Initiation in Latin America and the Caribbean: Late Testers and Late Presenters
(2011) Crabtree-Ramirez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E.; Wehbe, Fernando; Cesar, Carina; Padgett, Denis; Koenig, Serena; Gotuzzo, Eduardo; Cahn, Pedro; McGowan, Catherine C.; Masys, Daniel R.; Sierra Madero, Juan; Cortes, Claudia
Background: Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region. Methodology: Cross-sectional analysis from 9817 HIV-infected treatment-naïve patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4(+) count ≤200 cells/mm(3) prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed. Principal findings: Among subjects starting HAART (n = 9817) who had baseline CD4(+) available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52-59]), Chile (80%[95%CI:77-82]), Haiti (76%[95%CI:74-77]), Honduras (91%[95%CI:87-94]), Mexico (79%[95%CI:75-83]), Peru (86%[95%CI:84-88]). The proportion of LHI statistically changed over time (except in Honduras) (p≤0.02; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02-1.45; OR 1.20, 95%CI:1.02-1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94-1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87-0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP. Conclusion: LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation are needed to maximize benefits from HAART in the region.
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.
Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.
(2014-1) IeDEA and ART Cohort Collaborations; Avila, D.; Althoff, K. N.; Mugglin, C.; Wools-Kaloustian, K.; Koller, M.; Dabis, F.; Nash, D.; Gsponer, T.; Sungkanuparph, S.; McGowan, Catherine C.; May, M.; Cooper, D.; Chimbetete, C.; Wolff, Marcelo; Collier, A.; McManus, H.; Davies, M. A.; Costagliola, D.; Crabtree-Ramirez, Brenda; Chaiwarith, R.; Cescon, A.; Cornell, M.; Diero, L.; Phanuphak, P.; Sawadogo, A.; Ehmer, J.; Eholie, S. P.; Li, P. C.; Fox, M. P.; Gandhi, N. R.; González, E.; Lee, C. K.; Hoffmann, C. J.; Kambugu, A.; Keiser, O.; Ditangco, R.; Prozesky, H.; Lampe, F.; Kumarasamy, N.; Kitahata, M.; Lugina, E.; Lyamuya, R.; Vonthanak, S.; Fink, Valeria; d'Arminio Monforte, A.; Luz, P. M.; Chen, Y. M.; Minga, A.; Casabona, J.; Mwango, A.; Choi, J. Y.; Newell, M. L.; Bukusi, E. A.; Ngonyani, K.; Merati, T. P.; Otieno, J.; Bosco, M. B.; Phiri, S.; Ng, O. T.; Anastos, Kathryn; Rockstroh, J.; Santos, I.; Oka, S.; Somi, G.; Stephan, C.; Teira, R.; Wabwire, D.; Wandeler, G.; Boulle, A.; Reiss, Peter; Wood, R.; Chi, B. H.; Williams, C.; Sterne, J. A.; Egger, M.
To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. Results: In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/mL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/mL (76% increase), 88 to 135 cells/mL (53%), and 209 to 274 cells/mL (31%). In 2009, compared with LIC, median counts were 13 cells/mL [95% confidence interval (CI): 256 to +30] lower in LMIC, 22 cells/mL (262 to +18) lower in UMIC, and 112 cells/mL (+75 to +149) higher in HIC. They were 23 cells/mL (95% CI: +18 to +28 cells/mL) higher in women than men. Median counts were 88 cells/mL (95% CI: +35 to +141 cells/mL) higher in countries with an estimated national cART coverage .80%, compared with countries with ,40% coverage. Conclusions: Median CD4 cell counts at the start of cART increased 2000–2009 but remained below 200 cells/mL in LIC and MIC and below 300 cells/mL in HIC. Earlier start of cART will require substantial efforts and resources globally.
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.
Lessons learned from over a decade of data audits in international observational HIV cohorts in Latin America and East Africa
(Cambridge University Press & The Association for Clinical and Translational Science, 2023-11) Lotspeich, Sarah C.; Shepherd, Bryan E.; Kariuki, Marion Achieng; Wools-Kaloustian, Kara; McGowan, Catherine C.; Musick, Beverly; Semeere, Aggrey; Crabtree-Ramirez, Brenda; Mkwashapi, Denna M.; Cesar, Carina; Ssemakadde, Matthew; Machado, Daisy Maria; Ngeresa, Antony; Ferreira, Flávia Faleiro; Lwali, Jerome; Marcelin, Adias; Cardoso, Sandra Wagner; Luque, Marco Tulio; Otero, Larissa; Cortes, Claudia; Duda, Stephany N.
Introduction: Routine patient care data are increasingly used for biomedical research, but such “secondary use” data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.
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.
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.
Use of Third Line Antiretroviral Therapy in Latin America
(2014-5) Cesar, Carina; Shepherd, Bryan; Jenkins, Cathy; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdile´a Goncalves; Cortes, Claudia; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine; Cahn, Pedro; Caribbean; Central and South America Network for HIV Epidemiology
Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.

Browsing by Author "Crabtree-Ramirez, Brenda"

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