Browsing by Author "Shepherd, Bryan E."

Now showing 1 - 7 of 7
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Duration of anti-tuberculosis therapy and timing of antiretroviral therapy initiation: association with mortality in HIV-related tuberculosis
    (2013) Cortes, Claudia; Wehbe, Firas H.; McGowan, Catherine C.; Shepherd, Bryan E.; Duda, Stephany N.; Jenkins, Cathy A.; Gonzalez, Elsa; Carriquiry, Gabriela; Schechter, Mauro; Padgett, Denis; Cesar, Carina; Sierra Madero, Juan; Pape, Jean W.; Masys, Daniel R.; Sterling, Timothy R. ; South American Network for HIV Research (CCASA-net) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
    Background Antiretroviral therapy (ART) decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. Methods We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. Results Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm3, 171 (68%) received >180 days of anti-tuberculosis therapy, 168 (66%) initiated anti-tuberculosis therapy before ART, and 43 (17%) died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02). In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007). Conclusions The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated.
  • Thumbnail Image
    Item
    Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in Latin America and the Caribbean: an observational cohort study
    (2015-11) Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Rocha Ribeiro, Sayonara; Cortes, Claudia; Pape, Jean W; Sierra Madero, Juan; Fink, Valeria; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro; Caribbean; Central and South America Network for HIV Epidemiology (CCASAnet) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Program
    Background: Access to combination antiretroviral therapy (ART) is expanding in Latin America (Mexico, Central America, and South America) and the Caribbean. We assessed the incidence of and factors associated with regimen failure and regimen change of initial ART in this region. Methods: This observational cohort study included antiretroviral-naive adults starting ART from 2000 to 2014 at sites in seven countries throughout Latin America and the Caribbean. Primary outcomes were time from ART initiation until virological failure, major regimen modification, and a composite endpoint of the first of virological failure or major regimen modification. Cumulative incidence of the primary outcomes was estimated with death considered a competing event. Findings: 14,027 patients starting ART were followed up for a median of 3.9 years (2.0-6.5): 8374 (60%) men, median age 37 years (IQR 30-44), median CD4 count 156 cells per μL (61-253), median plasma HIV RNA 5.0 log10 copies per mL (4.4-5.4), and 3567 (28%) had clinical AIDS. 1719 (12%) patients had virological failure and 1955 (14%) had a major regimen change. Excluding the site in Haiti, which did not regularly measure HIV RNA, cumulative incidence of virological failure was 7.8% (95% CI 7.2-8.5) 1 year after ART initiation, 19.2% (18.2-20.2) at 3 years, and 25.8% (24.6-27.0) at 5 years; cumulative incidence of major regimen change was 5.9% (5.3-6.4) at 1 year, 12.7% (11.9-13.5) at 3 years, and 18.2% (17.2-19.2) at 5 years. Incidence of major regimen change at the site in Haiti was 10.7% (95% CI 9.7-11.6) at 5 years. Virological failure was associated with younger age (adjusted hazard ratio [HR] 2.03, 95% CI 1.68-2.44, for 20 years vs 40 years), infection through injection drug use (vs infection through heterosexual sex; 1.60, 1.02-2.52), and initiation in earlier calendar years (1.28, 1.13-1.46, for 2002 vs 2006), but was not significantly associated with boosted protease inhibitor-based regimens (vs non-nucleoside reverse transcriptase inhibitor; 1.17, 1.00-1.36). Interpretation: Incidence of virological failure in Latin America and the Caribbean was generally lower than that reported in North America or Europe. Our results suggest the need to design strategies to reduce failure and major regimen change in young patients and those with a history of injection drug use.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Mortality During the First Year of Potent Antiretroviral Therapy in HIV-1-Infected Patients in 7 Sites Throughout Latin America and the Caribbean
    (2009) Tuboi, Suely H.; Schechter, Mauro; McGowan, Catherine C.; Cesar, Carina; Krolewiecki, Alejandro J.; Cahn, Pedro; Wolff, Marcelo; Pape, Jean W.; Padgett, Denis; Sierra Madero, Juan; Gotuzzo, Eduardo; Masys, Daniel R.; Shepherd, Bryan E.
    Background: Although nearly 2 million people live with HIV in Latin America and the Caribbean, mortality rates after initiation of highly active antiretroviral therapy (HAART) have not been well described. Methods: Five thousand one hundred fifty-two HIV-infected, antiretroviral-naive adults from clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru starting HAART during 1996-2007 were included. First-year mortality rates and their association with demographics, regimen, baseline CD4, and clinical stage were assessed. Results: Overall 1-year mortality rate was 8.3% [95% confidence interval (CI): 7.6% to 9.1%], although variable across sites: 2.6%, 3.7%, 6.0%, 13.0%, 10.8%, 3.5%, and 9.8% for clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru, respectively. Eighty percent of deaths occurred within the first 6 months. Median baseline CD4 was 107 cells per milliliter, ranging from 79 (Peru) to 163 (Argentina). Mortality estimates adjusting for CD4 were similar across sites (1.1%-2.8% for CD4 = 200), except for Haiti, 7.5%, and Honduras, 7.0%. Death was associated with lower CD4 [adjusted hazard ratio for CD4 = 200 vs. CD4 = 50 was 0.58; 95% CI: 0.40 to 0.85] and clinical AIDS (hazard ratio = 3.1; 95% CI: 2.1 to 4.5). Conclusions: Mortality rates were similar to those reported elsewhere for resource-limited settings. Disease stage at HAART initiation, treatment eligibility criteria, program age, and background mortality rates may explain some variability in prognosis between sites.
  • Thumbnail Image
    Item
    Rates and Reasons for Early Change of First HAART in HIV-1-Infected Patients in 7 Sites throughout the Caribbean and Latin America
    (2010) Cesar, Carina; Shepherd, Bryan E.; Krolewiecki, Alejandro J.; Fink, Valeria; Schechter, Mauro; Tuboi, Suely H.; Wolff, Marcelo; Pape, Jean W.; Leger, Paul; Padgett, Denis; Sierra Madero, Juan; Gotuzzo, Eduardo; Sued, Omar; McGowan, Catherine C.; Masys, Daniel R.; Cahn, Pedro; Caribbean, Central and South America Network for HIV Research (CCASAnet) Collaboration; International Epidemiologic Databases to Evaluate AIDS (IeDEA) Program
    Background: HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%-70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. Methodology: Antiretroviral-naïve patients >or= 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. Principal findings: Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31-44), and median CD4 count was 105 cells/uL (IQR, 38-200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15-17%) and 28% (95% CI 27-29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1-2.6) and 2.1 (95% CI 1.7-2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1-1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens. Conclusions: Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation.