Browsing by Author "Wolff, Marcelo"
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Item 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 CBackground: 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.Item 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 RHow 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.Item Efficacy and Safety of Emtricitabine vs Stavudine in Combination Therapy in Antiretroviral-Naive Patients(2004) Saag, Michael S.; Cahn, Pedro; Raffi, Francois; Wolff, Marcelo; Pearce, David; Molina, Jean-Michel; Powderly, William; Shaw, Aaron L.; Mondou, Eric; Hinkle, Jonathan; Borroto-Esoda, Kristina; Quinn, John B.; Barry, David W.; Rousseau, Frederic; FTC-301A Study TeamContext: Tenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue reverse transcriptase inhibitor. Objective: To evaluate the efficacy and safety of tenofovir DF compared with stavudine in antiretroviral-naive patients. Design, setting, and participants: A prospective, randomized, double-blind study conducted at 81 centers in the United States, South America, and Europe from June 9, 2000, to January 30, 2004. A total of 753 patients infected with HIV who were antiretroviral naive were screened and 602 patients entered the study. Intervention: Patients were randomized to receive either tenofovir DF (n = 299) or stavudine (n = 303), with placebo, in combination with lamivudine and efavirenz. Main outcome measure: Proportion of patients with HIV RNA levels of less than 400 copies/mL at week 48. Results: In the primary intent-to-treat analysis in which patients with missing data or who added or switched antiretroviral medications before week 48 were considered as failures, the proportion of patients with HIV RNA of less than 400 copies/mL at week 48 was 239 (80%) of 299 in patients receiving tenofovir DF and 253 (84%) of 301 in patients receiving stavudine (95% confidence interval, -10.4% to 1.5%), exceeding the predefined -10% limit for equivalence. However, equivalence was demonstrated in the secondary analyses (HIV RNA <50 copies/mL) at week 48 and through 144 weeks. Virologic failure was associated most frequently with efavirenz and lamivudine resistance. Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups, respectively (P =.06). A more favorable mean change from baseline in fasting lipid profile was noted in the tenofovir DF group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n = 170] vs +134 mg/dL for stavudine [n = 162], P<.001), total cholesterol (+30 mg/dL [n = 170] vs +58 mg/dL [n = 162], P<.001), direct low-density lipoprotein cholesterol (+14 mg/dL [n = 169] vs +26 mg/dL [n = 161], P<.001), and high-density lipoprotein cholesterol (+9 mg/dL [n = 168] vs +6 mg/dL [n = 154], P =.003). Investigator-reported lipodystrophy was less common in the tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58 [19%] of 301, P<.001). The number of bone fractures and the renal safety profile were similar between the 2 groups. Conclusions: Through 144 weeks, the combination of tenofovir DF, lamivudine, and efavirenz was highly effective and comparable with stavudine, lamivudine, and efavirenz in antiretroviral-naive patients. However, tenofovir DF appeared to be associated with better lipid profiles and less lipodystrophy.Item 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.Item 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.Item 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.Item 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; CCASAnetObjective: 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.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.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) ProgramBackground: 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.Item Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America(2016-06-07) Crabtree-Ramírez, Brenda; Caro-Vega, Yanink; Shepherd, Bryan E; Grinsztejn, Beatriz; Wolff, Marcelo; Cortes, Claudia; Padgett, Denis; Carriquiry, Gabriela; Fink, Valeria; Jayathilake, Karu; Person, Anna K; McGowan, Catherine; Sierra-Madero, Juan; Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet), of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) ProgramBackground Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in “real life” settings in Latin America has not been evaluated. Methods Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) ≥18 years of age at enrolment, from 2001–2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS-defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. Results A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8–12.1) weeks before 2009 to 4.3 (IQR 2.0–7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). Discussion The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the publication of evidence of its benefit. We found important heterogeneity between sites which may reflect differences in clinical practices, local guidelines, and access to HAART. The impact of the timing of HAART initiation after OI on patient survival in this “real life” context needs further evaluation.