22 results on '"Ribaudo, Heather J"'
Search Results
2. Ideal cardiovascular health, biomarkers, and coronary artery disease in persons with HIV
- Author
-
Douglas, Pamela S., McCallum, Sara, Lu, Michael T., Umbleja, Triin, Fitch, Kathleen V., Foldyna, Borek, Zanni, Markella V., Fulda, Evelynne S., Bloomfield, Gerald S., Fichtenbaum, Carl J., Overton, Edgar T., Aberg, Judith A., Malvestutto, Carlos D., Burdo, Tricia H., Arduino, Roberto C., Ho, Ken S., Yin, Michael T., Ribaudo, Heather J., and Grinspoon, Steven K.
- Published
- 2023
- Full Text
- View/download PDF
3. Diet in a global cohort of adults with HIV at low-to-moderate traditional cardiovascular disease risk
- Author
-
Fitch, Kathleen V., McCallum, Sara A., Erlandson, Kristine M., Overton, Edgar Turner, Zanni, Markella V., Fichtenbaum, Carl, Aberg, Judith A., Fulda, Evelynne S., Kileel, Emma M., Moran, Laura E., Bloomfield, Gerald S., Novak, Richard M., Pérez-Frontera, Sigrid, Abrams-Downey, Alexandra, Pierone, Gerald, Kumarasamy, Nagalingeswaran, Ruxrungtham, Kiat, Mngqibisa, Rosie, Douglas, Pamela S., Ribaudo, Heather J., and Grinspoon, Steven K.
- Published
- 2022
- Full Text
- View/download PDF
4. Successful recruitment of a multi-site international randomized placebo-controlled trial in people with HIV with attention to diversity of race and ethnicity: critical role of central coordination.
- Author
-
Fitch, Kathleen V., Kileel, Emma M., Looby, Sara E., Zanni, Markella V., Sanchez, Laura R., Fichtenbaum, Carl J., Overton, Edgar T., Malvestutto, Carlos, Aberg, Judith A., Klingman, Karin L., Alston-Smith, Beverly, Lavelle, Judith, Rancourt, Anne, Badal-Faesen, Sharlaa, Cardoso, Sandra Wagner, Avihingsanon, Anchalee, Patil, Sandesh, Sponseller, Craig A., Melbourne, Kathleen, and Ribaudo, Heather J.
- Subjects
ETHNICITY ,MINORITY women ,AFRICAN Americans ,MINORITIES - Abstract
Background: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is a multicenter, randomized, placebo-controlled trial, designed to test whether a statin medication can prevent cardiovascular disease in people with HIV. REPRIEVE recently completed enrollment of 7557 participants at over 100 clinical sites globally. Participant groups of focus were women, and racial and ethnic minorities. Objective: To describe recruitment methods and strategies developed by the REPRIEVE Clinical Coordinating Center (CCC) and share best practices learned from the recruitment process. Methods: Enrollment targets were agreed upon with the primary funder, the National Heart, Lung, and Blood Institute (NHLBI) and were milestone driven. Milestones included number of sites activated, number of participants enrolled within specific time frames, and proportion of women and minorities enrolled. Strategies to achieve these milestones included structured interviews with site-designated REPRIEVE Recruitment Champions to develop best practices, development of a multimedia campaign, and site level recruitment support. Results: Recruitment initiated March, 2015 and completed March, 2019. The final accrual target was 7500 participants over 48 months. The trial met this target within the time specified. Overall, 10,613 screens were completed, 48% of participants enrolled from sites outside of North America, 32% were female, 44% were Black or African American, and 25% were Hispanic or Latino. Conclusions: REPRIEVE met its overall projected recruitment goal by using multiple, simultaneous strategies to specifically target a diverse population including minority subgroups. REPRIEVE benefited from the development of recruitment strategies with clear targets and communication of accrual targets to study teams. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
5. Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).
- Author
-
Grinspoon, Steven K., Fitch, Kathleen V., Overton, Edgar Turner, Fichtenbaum, Carl J., Zanni, Markella V., Aberg, Judith A., Malvestutto, Carlos, Lu, Michael T., Currier, Judith S., Sponseller, Craig A., Waclawiw, Myron, Alston-Smith, Beverly, Cooper-Arnold, Katharine, Klingman, Karin L., Desvigne-Nickens, Patrice, Hoffmann, Udo, Ribaudo, Heather J., Douglas, Pamela S., and REPRIEVE Investigators
- Abstract
Background: Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score >7.5% (LDL-C <190 mg/dL for risk score <7.5%, LDL-C <160 mg/dL for risk score 7.6%-10%, and LDL-C<130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety.Results: To date, REPRIEVE has enrolled >7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial.Conclusions: REPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
6. Vitamin D does not Modulate Immune-Mediated Bone loss during ART Initiation
- Author
-
Yin, Michael T, Chan, Ellen S, Brown, Todd T, Kinslow, Jennifer, Martinson, Jeffrey, Landay, Alan, Melbourne, Kathleen M, Ribaudo, Heather J, and Overton, Edgar T
- Abstract
Background Vitamin D (VitD) and calcium (Ca) supplementation attenuates antiretroviral therapy (ART)-associated bone loss, but it is unclear whether this effect is mediated through immunomodulation.Methods In this exploratory analysis of A5280, a 48-week, randomized, double-blind, placebo-controlled study of VitD/Ca supplementation with ART initiation, we characterized lymphocyte phenotypes and receptor activator of nuclear factor kappa-B ligand (RANKL) expression by median fluorescence intensity (MFI) at baseline and 48 weeks. Changes were evaluated within and between treatment groups by Wilcoxon signed rank and rank sum tests, respectively. Spearman correlations estimated relationships between cellular phenotypes and bone mineral density (BMD).Results Of 165 participants enrolled, 138 had samples for cellular phenotypes (64 VitD/Ca, 74 placebo). Markers of CD4, CD8 activation (CD38+HLA-DR+) declined (all P<0.001), but did not differ between arms. There was no decline in either %T-cells (CD4 and CD8) expressing RANKL or expression of RANKL by MFI. CD4 and CD8 activation markers were not correlated with BMD at baseline (r<0.15 and P>0.09 for all), but greater declines in CD4 activation correlated with greater declines in hip and spine BMD in both arms (0.25 =r =0.37, all P<0.05). A greater decline in CD8 activation was correlated with greater declines in both hip and spine BMD in the placebo arm only (hip r=0.31, P=0.009; spine r=0.25, P=0.035).Conclusions Reductions in T-cell activation are characteristic of ART initiation, but only correlated modestly with bone loss. VitD/Ca supplementation does not appear to mitigate bone loss through modulation of immune activation or expression of RANKL. Trial registration number: NCT01403051.
- Published
- 2019
- Full Text
- View/download PDF
7. Hyperlipidaemia in HIV-Infected Patients on Lopinavir/Ritonavir Monotherapy in Resource-Limited Settings
- Author
-
Matoga, Mitch M, Hosseinipour, Mina C, Aga, Evgenia, Ribaudo, Heather J, Kumarasamy, Nagalingeswaran, Bartlett, John, and Hughes, Michael D
- Abstract
Background Cardiovascular disease (CVD) is an emerging concern for HIV-infected patients. Hyperlipidaemia is a risk factor for CVD and a complication of protease-inhibitor-based antiretroviral therapy, but little is known about its incidence and risk factors in treated patients in resource-limited settings (RLS).Methods We conducted a secondary analysis of ACTG A5230 trial in which HIV-infected adults from India, Malawi, Tanzania, Thailand and South Africa, with virological relapse on first-line therapy were initiated on lopinavir/ritonavir (LPV/r) monotherapy. Hyperlipidaemia was a grade 2+ elevated fasting total cholesterol (FTC=240 mg/dl) or fasting triglycerides (FTG=500 mg/dl) or calculated low-density lipoprotein cholesterol (LDL=160 mg/dl) based on measurements at weeks 12, 24, 48, 68 and 104. We evaluated factors potentially associated with quantitative lipid changes from baseline to week 12. These were age, sex, race, site and baseline body mass index, CD4+T-cell count, HIV-1 RNA level and lipids.Results 106 participants without hyperlipidaemia at baseline started LPV/r; median age 39 years, 68% Black African, 55% female. The cumulative incidence of hyperlipidaemia at week 104 was 48% (95% CI 36, 58%). At week 12, there were significant mean increases from baseline in FTC (17 mg/dl, P<0.001) and FTG (104 mg/dl, P<0.001). In multivariable analysis, higher baseline FTC (P=0.044), FTG (P=0.025), Thai (P<0.001) or Indian sites (P=0.020) versus African sites were associated with increased risk of hyperlipidaemia.Conclusions In HIV-infected adults in RLS initiating LPV/r, hyperlipidaemia was common. Baseline lipid measurements and routine monitoring should be recommended in individuals starting LPV/r-based treatments with borderline high lipids.
- Published
- 2017
- Full Text
- View/download PDF
8. Changes in Plasma Levels of Oxidized Lipoproteins and Lipoprotein Subfractions with Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy and Associations with Common Carotid Artery Intima-Media Thickness: ACTG 5260s
- Author
-
Kelesidis, Theodoros, Tran, Thuy Tien T, Brown, Todd T, Moser, Carlee, Ribaudo, Heather J, Dube, Michael P, Yang, Otto O, McComsey, Grace A, Stein, James H, and Currier, Judith S
- Abstract
Background The role of oxidized lipoproteins (high-density [HDLox] and low-density [LDLox]) and total lipoprotein particle (Lp) number and size in HIV-related cardiovascular disease (CVD) is unclear. The goal of this study was to evaluate changes of these biomarkers and their associations with rate of carotid intima media thickness progression over 3 years (?CIMT) in chronic HIV infection.Methods Prospective study of 234 HIV-infected anti-retroviral treatment-naive participants without CVD who were randomized to receive tenofovir-emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir or raltegravir (RAL) and achieved plasma HIV-1 RNA <50 copies/ml by week 24 and thereafter. Biomarker changes over 24, 48 or 96 weeks from baseline and pairwise treatment group comparisons were examined. Associations of these bio-markers with dCIMT were analysed with mixed effects linear regression.Results HDLp number increased with both protease inhibitors (PIs) over 48 weeks, while LDLp number declined with RAL; Lp size did not change. Over 96 weeks, normalized HDLox declined with both PIs; LDLox increased in all groups. Few treatment group differences were observed across all biomarkers. Associations between ?CIMT and oxidized lipoproteins at all time points were not apparent (P=0.10). There was some evidence of slower ?CIMT for higher HDLp number (P=0.06) and for lower LDLp number (P=0.08) measured at baseline.Conclusions Unexpectedly, LDLox increased modestly in all treatment groups after ART initiation. Associations of plasma HDLox and LDLox with ?CIMT were not apparent. While plasma levels of abnormal lipoproteins have been shown to be associated with CVD outcomes, clear associations with sub-clinical atherosclerosis progression were not apparent in our study.
- Published
- 2017
- Full Text
- View/download PDF
9. Differential CD4+cell count increase and CD4+ : CD8+ratio normalization with maraviroc compared with tenofovir
- Author
-
Chan, Ellen S., Landay, Alan L., Brown, Todd T., Ribaudo, Heather J., Mirmonsef, Paria, Ofotokun, Igho, Weitzmann, M. Neale, Martinson, Jeffrey, Klingman, Karin L., Eron, Joseph J., Fichtenbaum, Carl J., Plants, Jill, and Taiwo, Babafemi O.
- Published
- 2016
- Full Text
- View/download PDF
10. A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness
- Author
-
Stein, James H., Ribaudo, Heather J., Hodis, Howard N., Brown, Todd T., Tran, Thuy Tien T., Yan, Mingzhu, Brodell, Elizabeth Lauer, Kelesidis, Theodore, McComsey, Grace A., Dube, Michael P., Murphy, Robert L., and Currier, Judith S.
- Abstract
Supplemental Digital Content is available in the text
- Published
- 2015
- Full Text
- View/download PDF
11. Comparison of Three Different FDA-Approved Plasma HIV-1 RNA Assay Platforms Confirms the Virologic Failure Endpoint of 200 Copies per Milliliter Despite Improved Assay Sensitivity
- Author
-
Lalama, Christina M., Jennings, Cheryl, Johnson, Victoria A., Coombs, Robert W., McKinnon, John E., Bremer, James W., Cobb, Bryan R., Cloherty, Gavin A., Mellors, John W., and Ribaudo, Heather J.
- Abstract
ABSTRACTDiscrepancies between HIV-1 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial participants during the second year of antiretroviral treatment were assayed with three FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, v1.5 (Monitor), the Abbott RealTime HIV-1 test on the m2000 system (Abbott), and the Roche TaqMan HIV-1 test, v2.0 (TaqMan). Samples from 61 additional participants with confirmed HIV-1 RNA levels of >50 copies/ml during trial follow-up were also included. Endpoints were HIV-1 RNA quantification of =50 copies/ml versus >50 copies/ml at an individual-sample level (primary) and determination of confirmed virologic failure (VF) from longitudinal samples. A total of 389 participants had results obtained from all assays on at least one sample (median = 6). Proportions of results of >50 copies/ml were 19% (Monitor), 22% (TaqMan), and 25% (Abbott). Despite indication of strong agreement (Cohen's kappa, 0.76 to 0.82), Abbott was more likely to detect HIV-1 RNA levels of >50 copies/ml than Monitor (matched-pair odds ratio [mOR] = 4.2; modified Obuchowski P< 0.001) and TaqMan (mOR = 2.1; P< 0.001); TaqMan was more likely than Monitor (mOR = 2.6; P< 0.001). Despite strong agreement in classifying VF across assay comparisons (kappa, 0.75 to 0.92), at a 50-copies/ml threshold, differences in the probability of VF classification (in the same direction as primary) were apparent (all McNemar's P< 0.007). At a 200-copies/ml VF threshold, no differences between assays were apparent (all P> 0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting HIV-1 RNA levels of >50 copies/ml and identifying VF at the 50-copies/ml threshold. This has important implications for the definition of VF in clinical trials and clinical practice.
- Published
- 2015
- Full Text
- View/download PDF
12. Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols
- Author
-
Lehmann, David S., Ribaudo, Heather J., Daar, Eric S., Gulick, Roy M., Haubrich, Richard H., Robbins, Gregory K., Bakker, Paul I.W. de, Haas, David W., and McLaren, Paul J.
- Abstract
Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols.
- Published
- 2015
- Full Text
- View/download PDF
13. Pharmacogenomics of HIV Therapy: Summary of a Workshop Sponsored by the National Institute of Allergy and Infectious Diseases.
- Author
-
Haas, David W., Kuritzkes, Daniel R., Ritchie, Marylyn D., Amur, Shashi, Gage, Brian F., Maartens, Gary, Masys, Dan, Fellay, Jacques, Phillips, Elizabeth, Ribaudo, Heather J., Freedberg, Kenneth A., Petropoulos, Christos, Manolio, Teri A., Gulick, Roy M., Haubrich, Richard, Kim, Peter, Dehlinger, Marjorie, Abebe, Rahel, Telenti, Amalio, and on behalf of participants in the workshop, Pharmacogenomics - A Path Towards Personalized HIV Care*
- Published
- 2011
14. Change in High-Sensitivity C-Reactive Protein Levels Following Initiation of Efavirenz-Based Antiretroviral Regimens in HIV-Infected Individuals.
- Author
-
Shikuma, Cecilia M., Ribaudo, Heather J., Zheng, Yu, Gulick, Roy M., Meyer, William A., Tashima, Karen T., Bastow, Barbara, Kuritzkes, Daniel R., and Glesby and the AIDS Clinical Trials Group A5095 Study Team, Marshall J.
- Abstract
AbstractElevations in C-reactive protein (CRP) are associated with increased cardiovascular disease (CVD) risk, increased HIV disease progression, and death in HIV-infected patients. Use of abacavir has been reported to increase CVD risk. We assessed the effect of virologically suppressive efavirenz (EFV)-based antiretroviral therapy on high sensitivity CRP (hsCRP) levels over a 96-week period with particular attention to the effect of gender and abacavir use. Banked sera from entry and week 96 visits of AIDS Clinical Trials Group A5095 participants were assayed for hsCRP, then analyzed by gender, abacavir randomization, and for correlation with changes in fasting metabolic parameters. Analyses of hsCRP were conducted in two phases and involved a total of 145 men and 51 women. hsCRP did not differ by gender at baseline but higher levels were seen at week 96 in women (median 6 mg/liter; Q1, Q3, 1.8, 13.8) compared to men (median 1.6 mg/liter; Q1, Q3, 0.9, 4.2, p< 0.001), with an estimated shift in hsCRP by gender of 2.5 mg/liter (95% CI 1.0, 5.1). There was no difference in hsCRP levels by abacavir use. Changes in hsCRP did not correlate with changes in insulin resistance or with changes in fasting lipids. Durably virologically suppressive therapy with EFV-based regimens did not decrease hsCRP levels over a 96-week period. hsCRP levels increased significantly only in women. Randomization to abacavir had no effect on changes in hsCRP levels. Changes in hsCRP levels did not correlate with changes in fasting metabolic parameters. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
15. Cost-Effectiveness Analysis of Ugt1A1Genetic Testing to Inform Antiretroviral Prescribing in HIV Disease
- Author
-
Schackman, Bruce R, Haas, David W, Becker, Jessica E, Berkowitz, Bethany K, Sax, Paul E, Daar, Eric S, Ribaudo, Heather J, and Freedberg, Kenneth A
- Abstract
Background Homozygosity for UGT1A1*28/*28has been reported to be associated with atazanavir-associated hyperbilirubinaemia and premature atazanavir discontinuation. We assessed the potential cost-effectiveness of UGT1A1testing to inform the choice of an initial protease-inhibitor-containing regimen in antiretroviral therapy (ART)-naive individuals.Methods We used the Cost-Effectiveness of Preventing AIDS Complications computer simulation model to project quality-adjusted life years (QALYs) and lifetime costs (2009 USD) for atazanavir-based ART with or without UGT1A1testing, using darunavir rather than atazanavir when indicated. We assumed the UGT1A1-associated atazanavir discontinuation rate reported in the Swiss HIV Cohort Study (a *28/*28frequency of 14.9%), equal efficacy and cost of atazanavir and darunavir and a genetic assay cost of $107. These parameters, as well as the effect of hyperbilirubinaemia on quality of life and loss to follow up, were varied in sensitivity analyses. Costs and QALYs were discounted at 3% annually.Results Initiating atazanavir-based ART at CD4+T-cell counts <500 cells/µl without UGT1A1testing had an average discounted life expectancy of 16.02 QALYs and $475,800 discounted lifetime cost. Testing for UGT1A1increased QALYs by 0.49 per 10,000 patients tested and was not cost-effective (>$100,000/QALY). Testing for UGT1A1was cost-effective (<$100,000/QALY) if assay cost decreased to $10, or if avoiding hyperbilirubinaemia by UGT1A1testing reduced loss to follow-up by 5%. If atazanavir and darunavir differed in cost or efficacy, testing for UGT1A1was not cost-effective under any scenario.Conclusions Testing for UGT1A1may be cost-effective if assay cost is low and if testing improves retention in care, but only if the comparator ART regimens have the same drug cost and efficacy.
- Published
- 2013
- Full Text
- View/download PDF
16. Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naive individuals with HIV infection
- Author
-
Stein, James H., Brown, Todd T., Ribaudo, Heather J., Chen, Yun, Yan, Mingzhu, Lauer-Brodell, Elizabeth, McComsey, Grace A., Dubé, Michael P., Murphy, Robert L., Hodis, Howard N., and Currier, Judith S.
- Abstract
To evaluate associations between traditional cardiovascular disease (CVD) risk factors, inflammatory markers and markers of HIV disease activity with ultrasonographic measures of CVD risk in patients with HIV who are not receiving antiretroviral therapy (ART).
- Published
- 2013
- Full Text
- View/download PDF
17. Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS Clinical Trials Group protocols implicates several CYP2B6variants
- Author
-
Holzinger, Emily R., Grady, Benjamin, Ritchie, Marylyn D., Ribaudo, Heather J., Acosta, Edward P., Morse, Gene D., Gulick, Roy M., Robbins, Gregory K., Clifford, David B., Daar, Eric S., McLaren, Paul, and Haas, David W.
- Abstract
Prior candidate gene studies have associated CYP2B6516G→T rs3745274 and 983T→C rs28399499 with increased plasma efavirenz exposure. We sought to identify novel variants associated with efavirenz pharmacokinetics.
- Published
- 2012
- Full Text
- View/download PDF
18. Lopinavirritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings
- Author
-
Bartlett, John A., Ribaudo, Heather J., Wallis, Carole L., Aga, Evgenia, Katzenstein, David A., Stevens, Wendy S., Norton, Michael R., Klingman, Karin L., Hosseinipour, Mina C., Crump, John A., Supparatpinyo, Khuanchai, Badal-Faesen, Sharlaa, Kallungal, Beatrice A., and Kumarasamy, Nagalingeswaran
- Abstract
To evaluate virologic response rates of lopinavirritonavir (LPVr) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs).
- Published
- 2012
- Full Text
- View/download PDF
19. Relationship between minority nonnucleoside reverse transcriptase inhibitor resistance mutations, adherence, and the risk of virologic failure
- Author
-
Li, Jonathan Z., Paredes, Roger, Ribaudo, Heather J., Svarovskaia, Evguenia S., Kozal, Michael J., Hullsiek, Katherine H., Miller, Michael D., Bangsberg, David R., and Kuritzkes, Daniel R.
- Abstract
To evaluate the risk of virologic failure conferred by suboptimal adherence to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and minority NNRTI resistance mutations.
- Published
- 2012
- Full Text
- View/download PDF
20. Design Issues in Initial HIV-Treatment Trials: Focus on Actg A5095
- Author
-
Ribaudo, Heather J, Kuritzkes, Daniel R, Schackman, Bruce R, Acosta, Edward P, Shikuma, Cecilia M, and Gulick, Roy M
- Abstract
ACTG (AIDS Clinical Trials Group) A5095 was a double-blinded Phase III clinical trial designed to compare three simple strategies for the initial treatment of HIV-1 infection: a non-nucleoside reverse transcriptase inhibitor (NNRTI) combined with two nucleosides, a triple-nucleoside regimen, and an NNRTI combined with three nucleosides. The study was designed to provide a rigorous evaluation of the relative effectiveness of the three different treatment strategies in achieving and maintaining durable HIV-1 RNA suppression using both superiority and non-inferiority designs. At the same time, we sought to provide study participants with flexible treatment management options that closely reflected clinical care approaches available outside the setting of a clinical trial in this rapidly changing field of medicine. Fulfilling both of these goals required making decisions about the primary endpoint definition, blinding, treatment changes, and stopping guidelines for the primary efficacy hypotheses. In this paper we describe the study design decisions that were made, in the context of randomized HIV treatment trials in general. We hope that the discussion will inform the design of treatment strategy trials, both for HIV and for other diseases where clinical standards change rapidly. We also hope to inform the field regarding issues in choosing composite versus virological endpoints as well as other key considerations in trial design and monitoring.
- Published
- 2006
- Full Text
- View/download PDF
21. A joint analysis of quality of life and survival using a random effect selection model
- Author
-
Ribaudo, Heather J., Thompson, Simon G., and Allen‐Mersh, Timothy G.
- Abstract
In studies of patients with advanced disease, longitudinal quality of life data may be truncated as a result of early death. Since survival and quality of life are likely to be related, modelling of the quality of life response needs to account for these different survival patterns. Here we discuss the application of a random effect selection model, in the form of a trivariate Normal model for the joint analysis of quality of life response (intercept and slope) and log survival time. Under certain assumptions this can give an unbiased description of the quality of life responses and valid inferences comparing treatment strategies in a clinical trial. It also indicates how quality of life and survival are related, by estimating the expected quality of life responses conditional on different survival times. Model parameters can be estimated using a restricted iterative generalized least‐squares (RIGLS) procedure within standard software, extended to handle censoring of survival outcome using an EM algorithm. The model is applied to a physical quality of life score and survival data from a trial of treatment for patients with colorectal hepatic metastases. Survival differed between the treatment groups, and quality of life repsonse tended to be worse, both in initial level and change over time, for those patients who died earlier. The parameter estimates obtained agreed well with those from analysing the extended trial data set with complete survival information. Residual diagnostics used to check the necessary underlying assumptions of the model are exemplified. We conclude that such models can give an informative description of longitudinal responses when these are truncated by differential survival patterns. Copyright © 2000 John Wiley & Sons, Ltd.
- Published
- 2000
- Full Text
- View/download PDF
22. A joint analysis of quality of life and survival using a random effect selection model
- Author
-
Ribaudo, Heather J., Thompson, Simon G., and Allen-Mersh, Timothy G.
- Abstract
In studies of patients with advanced disease, longitudinal quality of life data may be truncated as a result of early death. Since survival and quality of life are likely to be related, modelling of the quality of life response needs to account for these different survival patterns. Here we discuss the application of a random effect selection model, in the form of a trivariate Normal model for the joint analysis of quality of life response (intercept and slope) and log survival time. Under certain assumptions this can give an unbiased description of the quality of life responses and valid inferences comparing treatment strategies in a clinical trial. It also indicates how quality of life and survival are related, by estimating the expected quality of life responses conditional on different survival times. Model parameters can be estimated using a restricted iterative generalized least-squares (RIGLS) procedure within standard software, extended to handle censoring of survival outcome using an EM algorithm. The model is applied to a physical quality of life score and survival data from a trial of treatment for patients with colorectal hepatic metastases. Survival differed between the treatment groups, and quality of life repsonse tended to be worse, both in initial level and change over time, for those patients who died earlier. The parameter estimates obtained agreed well with those from analysing the extended trial data set with complete survival information. Residual diagnostics used to check the necessary underlying assumptions of the model are exemplified. We conclude that such models can give an informative description of longitudinal responses when these are truncated by differential survival patterns. Copyright © 2000 John Wiley & Sons, Ltd.
- Published
- 2000
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.