Browsing by Author "Cesar, Carina"

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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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    A phase 4, single-arm, open-label, pilot study of maraviroc, raltegravir and darunavir/r in HIV-1 adults with triple class failure: TERCETO study
    (2012) Patterson, Patricia; Magneres, Claudia; Sued, Omar; Fink, Valeria; Figueroa, Maria Ines; Cesar, Carina; Gun, Ana; Cahn, Pedro; Krolewiecki, Alejandro J.
    The purpose of this phase 4, single-arm, open-label study was to evaluate the safety, tolerability, efficacy, antiviral and immunological activity of maraviroc (MVC) in combination with raltegravir (RGV) and darunavir/r (DRV/r) in adult HIV-1 infected patients (pts) with limited treatment options. HIV-1 pts with documented virologic triple class failure or multi-drug class resistance defined as the presence of Q151 complex, 69 insertion complex and/or≥3 TAMs for NRTIs and K103N, G190S+Y181C or Y188L mutants for NNRTIs and≥3 RAMs (L10F/I/R/V; M46I/L; I54V/M/L; V82A/F/T/S; I84V; L90M) for protease inhibitors (PIs) were offered a triple drug regimen consisting of MVC 150 mg BID, RGV 400 mg BID and DRV/r 600/100 mg BID. Safety, lipid profile and virologic efficacy were evaluated at week 4, 12, 24, 36 and 48. Between January 2010 and March 2012, 27 pts were enrolled. Screening failure rate was 52% due to undetectable viral load (pVL) or non R5 tropism type (Trofile™). Despite being heavily pre-treated pts, only 26% had negative tropism test at SCR. Baseline characteristics of 13 included pts were: 77% male, median age 43 years (IQR: 40.1–48.6), 38% had a prior AIDS-defining condition. Median BSL pVL was 23,350 cps/mL (4.4 log10) (IQR: 11,236–55,785) and median CD4 was 222 cells/mm3 (IQR: 179–318). Median time on NRTIs, NNRTIs and PIs were 10.7 (8.6–13.7), 1.7 (1.3–7.6) and 5.4 (4.7–10) years respectively. Pts had received a median of 2 PIs (IQR: 2–3). 8/13 pts showed thymidine analogue-associated mutations (TAMs), and≥2 were present in 5/13. Detectable NNRTI resistance-associated mutations (RAMs) were present in 10/13 patients. 9/13 had≥4 primary PI RAMs. At 48 weeks, 2 pts had discontinued therapy (OIs related death (cryptococcal meningitis)=1, withdrawn from the study on W36 due to blips despite not achieving criteria for virologic failure=1) and the remaining pts (11/13) achieved undetectable pVL and increased CD4 in 133 cell/mm3 from BSL (IQR: 81–174.5). Median total cholesterol levels increased from 162 mg/dL (IQR: 135-188) to 215 mg/dL (IQR: 182–237) between BSL/W48; median change in cholesterol levels: 40 mg/dL (IQR: 6.5-66). Salvage therapy including MVC, RGV and DRV/r achieved sustained reductions in pVL (<50 copies/mL) through 48 weeks of therapy in this pilot study with no treatment limiting toxicity.
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    A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts
    (2016-04-04) Althoff, Keri N; Rebeiro, Peter F; Hanna, David B; Padgett, Denis; Horberg, Michael A; Grinsztejn, Beatriz; Abraham, Alison G; Hogg, Robert; Gill, M John; Wolff, Marcelo J; Mayor, Angel; Rachlis, Anita; Williams, Carolyn; Sterling, Timothy R; Kitahata, Mari M; Buchacz, Kate; Thorne, Jennifer E; Cesar, Carina; Cordero, Fernando M; Rourke, Sean B; Sierra-Madero, Juan; Pape, Jean W; Cahn, Pedro; McGowan, Catherine
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    Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters
    (2011) Socias, Maria E.; Sued, Omar; Laufer, Natalia; Lázaro, Maria E.; Mingrone, Hugo; Remondegui, Claudio; Figueroa, Maria Ines; Cesar, Carina; Gun, Ana; Turk, Gabriela; Bouzas, Maria B.; Kavasery, Rosanna; Krolewiecki, Alejandro J.; Perez, Hector; Salomon, Horacio; Pryluka, Damian
    Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.
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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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    Biterapia con atazanavir/ritonavir más raltegravir versus terapia triple en segunda línea: Ensayo ARTE
    (Fundación Huésped - Sociedad Argentina de Infectología, 2023-07) Figueroa, María Inés; Sued, Omar; Cesar, Carina; Patterson, Patricia; Yamamoto, Cleyton; Fink, Valeria; Luna, Norma; Camiro-Zúñiga, Antonio; Gun, Ana; Cahn, Pedro
    Antecedentes: La terapia dual ha surgido como un nuevo concepto para el tratamiento del VIH. Este estudio tenía como objetivo comparar un régimen dual basado en ATV/r + RAL (TD) frente a estándar de tres drogas con ATV/r + TDF/FTC (TT) luego del fracaso de un primer esquema ba- sado en INNTR.ClinicalTrials.gov, Número: NCT01829802. Método: Estudio piloto abierto, multicéntrico y aleatoriza- do. Resultado primario: proporción de sujetos con ARN del VIH-1 menor a 50 copias/mL en semana 48 (S48). Resulta- dos secundarios: discontinuaciones asociadas a eventos adversos (EA), tiempo transcurrido hasta la supresión viral, desarrollo de mutaciones de resistencia a la integrasa y proteasa, cambio en recuento de CD4. Resultados: De los 57 participantes seleccionados, 34 fue- ron asignados aleatoriamente para recibir: TD (n: 18) o TT (n: 16). En semana 48, 67% (n: 12/18) en TD tuvo respues- ta virológica y 88% (n: 14/16) en rama según el análisis FDA, intención de tratamiento/expuestos (p = NS) y 73% (TD) y 93% (TT) según análisis por protocolo (p = NS). El cambio de CD4 entre basal - S48: +119 y +52 células/μL en DT y TT, respectivamente. Cuatro participantes en TD y uno en TT presentaron fracaso virológico en la semana 48. Un participante desarrolló una mutación de resistencia a integrasa (155H). Conclusión: ATV/r+RAL como terapia dual de segunda línea mostró una tendencia al fracaso virológico más frecuente, en comparación con TT, aunque el estudio piloto no tenía potencia para demostrar esta diferencia. Este estudio está registrado en ClinicalTrials.gov, Número: NCT01829802.
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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.
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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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    Clinical-epidemiological features of HIV-infected patients diagnosed at age of 50 years or older
    (2012) Patterson, Patricia; Cahn, Susana; Sued, Omar; Fink, Valeria; Figueroa, Maria Ines; Cesar, Carina; Rojo, Marina; Ben, Graciela; Vazquez, Mariana; Cahn, Pedro
    HIV/AIDS prevention and care efforts are directed to individuals of reproductive age (15–49 yrs). With the extension of sexual life of older people, they became a growing population at risk of HIV infection, usually not included in prevention strategies. In order to evaluate clinical profile of HIV/AIDS pts diagnosed at 50 yrs or older assisted in an HIV outpatient center in Buenos Aires, we retrospectively assessed clinical records of pts initiating care between Jan 1986 and Dec 2011. Age, CD4 cells and viral load (pVL) at HIV diagnosis and most recent value, opportunistic infections (OIs), co-morbidities and antiretroviral therapy (ARV) were recorded. Of 10,998 pts assisted in the 26-yr period, 495 (4.5%) were≥50 yrs old at HIV diagnosis; median annual diagnoses: 18.5 (IQR 3.3–30.3) without significant changes in the last 20 yrs. Demographics: median age 54.7 yrs (IQR 51.8–59.2, rank 50–80), 76.6% male. Risk behavior: HTX 61.4%, MSM 34.1%, others 4.4%. 55.4% of HIV diagnoses occurred during hospitalization or simultaneously with acute OIs. One third (n=176) had AIDS at diagnosis, 24% had history of STDs. HCV co-infection 5.7%, past HBV infection 28.1% and chronic HBV infection 5.1%. Median CD4 cells at HIV diagnosis: 223.5 (13.7%) (IQR 98.8–420.3), initial pVL 60,000 cp/mL (IQR 9,995.5–208,391). 69.3% of pts started ARV therapy during follow-up (FU), and the median time between diagnosis and treatment initiation was 3.4 mo (IQR 0.7–14); 56.9% of them started a non-nucleoside-based regimen (ZDV/3TC/EFV), 28.3% a PI-based regimen (ZDV/3TC/IDV) and 14.6% a nucleoside-based regimen (ZDV/ddI pre-HAART era). After a year (±6 mo), 63.8% pts achieved undetectable pVL and gained 136 CD4 cells from BSL (IQR 83–204). After 40.6 mo of FU (IQR 6.7-89.8), 66.3% are alive, 7.1% died (68.6% of HIV-related diseases) and 26.7% are lost to FU. Co-morbidities were present in 125 (25.3%), mainly hypertension, increased lipids, CVD and DBT. Among treated pts, 70.6% achieved pVL<50 cp/mL, with a median increase of CD4 cells up to 410 (22%) (IQR 281.5–563.9) from BSL. 51% (176) changed ARV therapy due to toxicity/AE: 54.5%, ARV failure: 29.5% and simplification: 14.8%. Stable HIV epidemic in older people reinforce the need of specific prevention approaches, while growing age of HIV individuals in care highlights to consider risks associated to older age. Late presentation to care needs to be specifically addressed. Response to treatment is remarkable high in this population.
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    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.
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    Decision-making in HIV clinical trials: a study with patients enrolled in antiretroviral trials
    (2021) Feijoo-Cid, Maria; Rivero-Santana, Amado; Moriña, David; Cesar, Carina; Fink, Valeria; Sued, Omar
    Abstract Objective: To explore the decisional process of people living with human immunodeficiency virus (HIV) currently enrolled in antiretroviral clinical trials. Method: Cross-sectional retrospective study. Outcome variables were reasons to participate, perceived decisional role (Control Preference Scale), the Decisional Conflict Scale and the Decisional Regret Scale. Descriptive statistics were calculated, and associations among these variables and with sociodemographic and clinical characteristics were analyzed with non-parametric techniques. Results: Main reasons to participate were gratitude towards Fundación Huesped (47%), the doctor's recommendation (32%), and perceived difficulty to access treatment in a public hospital (28%). Most patients thought that they made their decision alone (54.8%) or collaboratively with the physician (43%). Decisional conflict was low, with only some conflict in the support subscale (median=16.67). Education was the only significant correlate of the total decisional conflict score (higher in less educated patients; p=0.018), whereas education, recent diagnosis, living alone, lower age, being man and doctor's recommendation to go to Fundación Huésped related to higher conflict in different subscales. Nobody regretted to participate. Conclusions: The decision making regarding participation in HIV trials, from the perspective of participants, was made respecting their autonomy and with very low decisional conflict. Currently, patients show no signs of regret. However, even in this favorable context, results highlight the necessity of enhancing the decision support in more vulnerable patients (e.g., less educated, recently diagnosed or with less social support), thus warranting equity in the quality of the decision making process. Keywords: Clinical trial; Conflicto decisional; Decisional conflict; Ensayo clínico; Human immunodeficiency virus; Participación del paciente; Patient participation; Virus de la inmunodeficiencia humana. ©2020 SESPAS. Published by Elsevier España, S.L.U. This is an open access article under the CCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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    Design and Development of an Electronic Health Record According to Argentine Gender Identity La
    (2022-06) Giraldo, Liliana; Fink, Valeria; Cahn, Florencia; Aristegui, Ines; Caceres, Betiana; Sued, Omar; Cesar, Carina
    Health information systems face the challenge of collecting data on patients’ gender identity. The absence of this information may lead the patients to situations of vulnerability and discrimination. The objective of this study is to describe the process of designing and developing an Electronic Health Record according to the Argentine Gender Identity Law. This health record allows clinics to record legal names and surnames, other social names, gender identity, sex at birth, and legal sex.
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    Dual therapy (ritonavir boosted atazanavir+raltegravir) versus standard triple therapy (ritonavir boosted atazanavir+tenofovir/emtricitabine) in patients failing first line therapy: 48 week results from a randomized pilot study
    (2018-08) Sued, Omar; Figueroa, MI; Cesar, Carina; Patterson, Patricia; Yamamoto, C; Fink, N; Gun, Ana; Cahn, Pedro
    Background: Dual therapy has emerged as a novel concept in treatment optimization in naive and supressed HIV patients. This study aimed at exploring virological response, safety and inflammation markers of a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among patients failing first NNRTI-containing treatment. Methods & Materials: Randomized open label pilot study. Primary outcome measures were proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/uL) and proportion of subjects discontinuing due to adverse events (AEs) during the first 48 weeks. ClinicalTrials.gov Identifier: NCT01829802. Results: Out of 57 patients screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At baseline 80% males, 50% MSM, median age 38 years, CDC stage C:35%, Median pVL: 3.9 Log10, CD4: 289 cells/uL. At week 48, data from 32 participants (2 did not reach week 48 yet) showed virological response in 69% (n: 11/16) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and 73% (DT) and 93% (TT) by per-protocol analysis (p = NS). CD4 cell count median change from baseline to week 48 was +119 and + 52 cell/uL in DT and TT, respectively. No deaths were recorded. Three SAEs occurred in 2 participants (pneumonia and stroke and, Belĺs paralysis), none related to study drugs. Eight Grade 2, probably drug-related AEs were observed: 1 in DT (gastrointestinal) and 7 in TT (5 gastrointestinal, 1 renal stone and 1 rash). Hyperbilirubinemia Grade 2/3 was seen in 77% in DT and 94% in TT, none requiring stopping ART. Two participants were discontinued due to loss of follow-up, one in each arm. Five participants had virological failure at W48, 4 in DT and 1 in TT, all with low pVL (52-589 copies/uL). One participant developed integrase resistance mutation and suppressed later on TT. Conclusion: ATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.
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    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.
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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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    Exploring the Decision‑Making Process of People Living with HIV Enrolled in Antiretroviral Clinical Trials: A Qualitative Study of Decisions Guided by Trust and Emotions
    (Springer Nature, 2023-07) Feijoo-Cid, Maria; Arreciado Marañón, Antonia; Huertas, Ariadna; Rivero-Santana, Amado; Cesar, Carina; Fink, Valeria; Fernández-Cano, María Isabel; Sued, Omar
    The informed consent is an ethical and legal requirement for potential participants to enroll in a study. There is ample of evidence that understanding consent information and enrollment is challenging for participants in clinical trials. On the other hand, the reasoning process behind decision-making in HIV clinical trials remains mostly unexplored. This study aims to examine the decision-making process of people living with HIV currently participating in antiretroviral clinical trials and their understanding of informed consent. We conducted a qualitative socio-constructivist study using semi-structured interviews. Eleven participants were selected by purposive sampling in Argentina until data saturation was reached. A content analysis was performed. The findings highlight the fact that some participants decided to enroll on the spot, while others made the decision a few days later. In all cases, the decision was based on different aspects of trust (in doctors, in the clinical research site, in the clinical trials system) but also on emotions associated with HIV and/or treatment. Moreover, while people living with HIV felt truly informed after the consent dialogue with a researcher, consent forms were unintelligible and unfriendly. The immediacy of patient decision-making has rarely been described before. Enrollment in an HIV clinical trial is mainly a trust-based decision but this does not contradict the ethical values of autonomy, voluntariness, non-manipulation, and non‐exploitation. Thus, trust is a key issue to be included in reshaping professional practices to ensure the integrity of the informed consent process.
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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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    Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America
    (2016-03-18) Cesar, Carina; Koethe, John R; Giganti, Mark J; Rebeiro, Peter; Althoff, Keri N; Napravnik, Sonia; Mayor, Angel; Grinsztejn, Beatriz; Wolff, Marcelo; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Sterling, Timothy R; Willig, James; Levison, Julie; Kitahata, Mari; Rodriguez-Barradas, Maria C; Moore, Richard D; McGowan, Catherine; Bryan E, Shepherd; Cahn, Pedro; for the Caribbean, Central and South America Network for HIV epidemiology (CCASAnet) and the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)
    Introduction Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). Conclusions HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.
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    HIV Viral Load Suppression in Adults and Children Receiving Antiretroviral Therapy—Results From the IeDEA Collaboration
    (2017-11-01) Jiamsakul, Awachana; Awachana, Azar; Althoff, Keri N; Cesar, Carina; Cortes, Claudia; Davies, Mary-Ann; Do, Viet Chau; Eley, Brian; Gill, John; Kumarasamy, Nagalingeswaran; Machado, Daisy Maria; Moore, Richard; Prozesky, Hans; Zaniewski, Elizabeth; Law, Matthew
    Machado