45 results on '"Boswell, Stephen L."'
Search Results
2. Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV‐positive individuals
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Caniglia, Ellen C, Robins, James M, Cain, Lauren E, Sabin, Caroline, Logan, Roger, Abgrall, Sophie, Mugavero, Michael J, Hernández‐Díaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R, Seage, George R, Bonnet, Fabrice, Le Marec, Fabien, Moore, Richard D, Reiss, Peter, van Sighem, Ard, Mathews, William C, Jarrín, Inma, Alejos, Belén, Deeks, Steven G, Muga, Roberto, Boswell, Stephen L, Ferrer, Elena, Eron, Joseph J, Gill, John, Pacheco, Antonio, Grinsztejn, Beatriz, Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Justice, Amy, Tate, Janet, Bucher, Heiner C, Egger, Matthias, Furrer, Hansjakob, Miro, Jose M, Casabona, Jordi, Porter, Kholoud, Touloumi, Giota, Crane, Heidi, Costagliola, Dominique, Saag, Michael, and Hernán, Miguel A
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Epidemiology ,Statistics ,Health Sciences ,Mathematical Sciences ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Adult ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Decision Making ,Drug Monitoring ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,RNA ,Viral ,Research Design ,Survival Analysis ,Viral Load ,causal inference ,dynamic regime ,joint treatment strategies ,marginal structural model ,no direct effect ,Public Health and Health Services ,Statistics & Probability - Abstract
Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.
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- 2019
3. Evaluating the Population Impact on Racial/Ethnic Disparities in HIV in Adulthood of Intervening on Specific Targets: A Conceptual and Methodological Framework
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Howe, Chanelle J, Dulin-Keita, Akilah, Cole, Stephen R, Hogan, Joseph W, Lau, Bryan, Moore, Richard D, Mathews, W Christopher, Crane, Heidi M, Drozd, Daniel R, Geng, Elvin, Boswell, Stephen L, Napravnik, Sonia, Eron, Joseph J, Mugavero, Michael J, and Systems, for the CFAR Network of Integrated Clinical
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Epidemiology ,Health Sciences ,Sexually Transmitted Infections ,Clinical Research ,Behavioral and Social Science ,Prevention ,Minority Health ,Infectious Diseases ,HIV/AIDS ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Ethnicity ,Female ,HIV ,HIV Infections ,Health Status Disparities ,Healthcare Disparities ,Humans ,Male ,Observational Studies as Topic ,Racial Groups ,United States ,health status disparities ,CFAR Network of Integrated Clinical Systems ,Mathematical Sciences ,Medical and Health Sciences - Abstract
Reducing racial/ethnic disparities in human immunodeficiency virus (HIV) disease is a high priority. Reductions in HIV racial/ethnic disparities can potentially be achieved by intervening on important intermediate factors. The potential population impact of intervening on intermediates can be evaluated using observational data when certain conditions are met. However, using standard stratification-based approaches commonly employed in the observational HIV literature to estimate the potential population impact in this setting may yield results that do not accurately estimate quantities of interest. Here we describe a useful conceptual and methodological framework for using observational data to appropriately evaluate the impact on HIV racial/ethnic disparities of interventions. This framework reframes relevant scientific questions in terms of a controlled direct effect and estimates a corresponding proportion eliminated. We review methods and conditions sufficient for accurate estimation within the proposed framework. We use the framework to analyze data on 2,329 participants in the CFAR [Centers for AIDS Research] Network of Integrated Clinical Systems (2008-2014) to evaluate the potential impact of universal prescription of and ≥95% adherence to antiretroviral therapy on racial disparities in HIV virological suppression. We encourage the use of the described framework to appropriately evaluate the potential impact of targeted interventions in addressing HIV racial/ethnic disparities using observational data.
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- 2018
4. Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study
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Caniglia, Ellen C, Cain, Lauren E, Sabin, Caroline A, Robins, James M, Logan, Roger, Abgrall, Sophie, Mugavero, Michael J, Hernández-Díaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R, Seage, George R, Bonnet, Fabrice, Dabis, Francois, Moore, Richard D, Reiss, Peter, van Sighem, Ard, Mathews, William C, del Amo, Julia, Moreno, Santiago, Deeks, Steven G, Muga, Roberto, Boswell, Stephen L, Ferrer, Elena, Eron, Joseph J, Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Justice, Amy C, Tate, Janet P, Gill, John, Pacheco, Antonio, Veloso, Valdilea G, Bucher, Heiner C, Egger, Matthias, Furrer, Hansjakob, Porter, Kholoud, Touloumi, Giota, Crane, Heidi, Miro, Jose M, Sterne, Jonathan A, Costagliola, Dominique, Saag, Michael, Hernán, Miguel A, Collaboration, HIV-CAUSAL, and Systems, Centers for AIDS Research Network of Integrated Clinical
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Medical Microbiology ,Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Infectious Diseases ,Sexually Transmitted Infections ,Clinical Research ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Developed Countries ,Drug Monitoring ,Europe ,Female ,HIV Infections ,HIV-1 ,Humans ,Male ,Middle Aged ,Prospective Studies ,Viral Load ,Young Adult ,HIV-CAUSAL Collaboration ,Centers for AIDS Research Network of Integrated Clinical Systems ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundClinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals.MethodsIn this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per μL, 350 cells per μL, and 500 cells per μL. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count.Findings47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4·0 months and viral load every 3·8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1·05 (95% CI 0·86-1·29) for threshold 200 and 1·02 (0·91·1·14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1·08 (0·95-1·22) for threshold 200 and 1·03 (0·96-1·12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2·01 (1·17-3·43) for threshold 200 and 1·24 (0·89-1·73) for threshold 350, and 24 month mean CD4 cell count differences were 0·4 (-25·5 to 26·3) cells per μL for threshold 200 and -3·5 (-16·0 to 8·9) cells per μL for threshold 350.InterpretationDecreasing monitoring to annually when CD4 count is higher than 200 cells per μL compared with higher than 500 cells per μL does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies.FundingNational Institutes of Health.
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- 2017
5. Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice
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Drozd, Daniel R, Saag, Michael S, Westfall, Andrew O, Mathews, William Chris, Haubrich, Richard, Boswell, Stephen L, Cole, Stephen R, Porter, Donna, Kitahata, Mari M, Juday, Timothy, and Rosenblatt, Lisa
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Biomedical and Clinical Sciences ,Clinical Sciences ,HIV/AIDS ,Comparative Effectiveness Research ,Prevention ,Adult ,Anti-Retroviral Agents ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Treatment Outcome ,ART ,atripla ,comparative effectiveness ,HIV ,single tablet regimen ,CFAR Network of Integrated Clinical Systems - Abstract
We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. Temporal trends in care may have confounded results.
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- 2017
6. Using observational data to emulate a randomized trial of dynamic treatment-switching strategies: an application to antiretroviral therapy
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Cain, Lauren E, Saag, Michael S, Petersen, Maya, May, Margaret T, Ingle, Suzanne M, Logan, Roger, Robins, James M, Abgrall, Sophie, Shepherd, Bryan E, Deeks, Steven G, Gill, M John, Touloumi, Giota, Vourli, Georgia, Dabis, François, Vandenhende, Marie-Anne, Reiss, Peter, van Sighem, Ard, Samji, Hasina, Hogg, Robert S, Rybniker, Jan, Sabin, Caroline A, Jose, Sophie, del Amo, Julia, Moreno, Santiago, Rodríguez, Benigno, Cozzi-Lepri, Alessandro, Boswell, Stephen L, Stephan, Christoph, Pérez-Hoyos, Santiago, Jarrin, Inma, Guest, Jodie L, Monforte, Antonella D’Arminio, Antinori, Andrea, Moore, Richard, Campbell, Colin NJ, Casabona, Jordi, Meyer, Laurence, Seng, Rémonie, Phillips, Andrew N, Bucher, Heiner C, Egger, Matthias, Mugavero, Michael J, Haubrich, Richard, Geng, Elvin H, Olson, Ashley, Eron, Joseph J, Napravnik, Sonia, Kitahata, Mari M, Van Rompaey, Stephen E, Teira, Ramón, Justice, Amy C, Tate, Janet P, Costagliola, Dominique, Sterne, Jonathan AC, Hernán, Miguel A, and Systems, and the HIV-CAUSAL Collaboration on behalf of the Antiretroviral Therapy Cohort Collaboration the Centers for AIDS Research Network of Integrated Clinical
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Epidemiology ,Health Sciences ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Female ,HIV Infections ,HIV-1 ,Humans ,Male ,Middle Aged ,Observational Studies as Topic ,Randomized Controlled Trials as Topic ,Survival Analysis ,United Kingdom ,Viral Load ,HIV ,antiretroviral therapy ,inverse-probability weighting ,observational studies ,mortality ,dynamic strategies ,Antiretroviral Therapy Cohort Collaboration ,the Centers for AIDS Research Network of Integrated Clinical Systems ,and the HIV-CAUSAL Collaboration ,Statistics ,Public Health and Health Services ,Public health - Abstract
BackgroundWhen a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).MethodsWe review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.ResultsOf 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.ConclusionsAlthough our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.
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- 2016
7. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries
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Caniglia, Ellen C, Sabin, Caroline, Robins, James M, Logan, Roger, Cain, Lauren E, Abgrall, Sophie, Mugavero, Michael J, Hernandez-Diaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R, Seage, George R, Bonnet, Fabrice, Dabis, Francois, Moore, Richard R, Reiss, Peter, van Sighem, Ard, Mathews, William C, del Amo, Julia, Moreno, Santiago, Deeks, Steven G, Muga, Roberto, Boswell, Stephen L, Ferrer, Elena, Eron, Joseph J, Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Olson, Ashley, Justice, Amy C, Tate, Janet P, Bucher, Heiner C, Egger, Matthias, Touloumi, Giota, Sterne, Jonathan A, Costagliola, Dominique, Saag, Michael, and Hernán, Miguel A
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Infectious Diseases ,Clinical Research ,HIV/AIDS ,Prevention ,Infection ,Good Health and Well Being ,AIDS-Related Complex ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Cohort Studies ,Developed Countries ,Europe ,HIV Infections ,Humans ,Prospective Studies ,RNA ,Viral ,United States ,Viral Load ,HIV ,CD4 cell count ,HIV RNA ,monitoring ,observational studies ,mortality ,Center for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
ObjectiveTo illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART).DesignProspective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems.MethodsAntiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes.ResultsIn 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies.ConclusionsOur findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.
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- 2016
8. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.
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Caniglia, Ellen C, Sabin, Caroline, Robins, James M, Logan, Roger, Cain, Lauren E, Abgrall, Sophie, Mugavero, Michael J, Hernandez-Diaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R, Seage, George R, Bonnet, Fabrice, Dabis, Francois, Moore, Richard R, Reiss, Peter, van Sighem, Ard, Mathews, William C, Del Amo, Julia, Moreno, Santiago, Deeks, Steven G, Muga, Roberto, Boswell, Stephen L, Ferrer, Elena, Eron, Joseph J, Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Olson, Ashley, Justice, Amy C, Tate, Janet P, Bucher, Heiner C, Egger, Matthias, Touloumi, Giota, Sterne, Jonathan A, Costagliola, Dominique, Saag, Michael, Hernán, Miguel A, and Center for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration
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Center for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration ,Humans ,HIV Infections ,AIDS-Related Complex ,RNA ,Viral ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Viral Load ,Cohort Studies ,Prospective Studies ,Developed Countries ,United States ,Europe ,HIV ,CD4 cell count ,HIV RNA ,monitoring ,observational studies ,mortality ,RNA ,Viral ,Virology ,Clinical Sciences ,Public Health and Health Services - Abstract
ObjectiveTo illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART).DesignProspective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems.MethodsAntiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes.ResultsIn 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies.ConclusionsOur findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.
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- 2016
9. High Levels of Antiretroviral Use and Viral Suppression Among Persons in HIV Care in the United States, 2010
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Dombrowski, Julia C, Kitahata, Mari M, Van Rompaey, Stephen E, Crane, Heidi M, Mugavero, Michael J, Eron, Joseph J, Boswell, Stephen L, Rodriguez, Benigno, Mathews, W Christopher, Martin, Jeffrey N, Moore, Richard D, and Golden, Matthew R
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Research ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,Infection ,Adolescent ,Adult ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Cross-Sectional Studies ,Drug Administration Schedule ,Female ,HIV ,HIV Infections ,Humans ,Male ,Middle Aged ,RNA ,Viral ,United States ,Viral Load ,Young Adult ,antiretroviral therapy ,highly active ,HIV infections/drug therapy ,HIV infections/prevention & control ,patient acceptance of health care/statistics and numerical data ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundContemporary data on patterns of antiretroviral therapy (ART) use in the United States are needed to inform efforts to improve the HIV care cascade.MethodsWe conducted a cross-sectional study of patients in the Centers for AIDS Research Network of Integrated Clinical Systems cohort who were in HIV care in 2010 to assess ART use and outcomes, stratified by nadir CD4 count (≤350, 351-500, or >500 cells/mm), demographics, psychiatric diagnoses, substance use, and engagement in continuous care (≥2 visits ≥3 months apart in 2010).ResultsOf 8633 patients at 7 sites who had ≥1 medical visit and ≥1 viral load in 2010, 94% had ever initiated ART, 89% were on ART, and 70% had an undetectable viral load at the end of 2010. Fifty percent of ART-naive patients had nadir CD4 counts >500 cells per cubic millimeter, but this group comprised just 3% of the total population. Among patients who were ART naive at the time of cohort entry (N = 4637), both ART initiation and viral suppression were strongly associated with nadir CD4 count. Comparing 2009 and 2010, the percentages of patients with viral suppression among those with nadir CD4 counts 351-500 and >500 cells per cubic millimeter were 44% vs. 57% and 25% vs. 33%, respectively. Engagement in care was the only factor consistently associated with ART use and viral suppression across nadir CD4 count strata.ConclusionsOur findings suggest that ART use and viral suppression among persons in HIV care may be more common than estimated in some previous studies and increased from 2009 to 2010.
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- 2013
10. Control of HIV-1 Viremia and Protection from AIDS are Associated with HLA-Bw4 Homozygosity
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Flores-Villanueva, Pedro O., Yunis, Edmond J., Delgado, Julio C., Vittinghoff, Eric, Buchbinder, Susan, Leung, Jessica Y., Uglialoro, Adele M., Clavijo, Olga P., Rosenberg, Eric S., Kalams, Spyros A., Braun, James D., Boswell, Stephen L., Walker, Bruce D., and Goldfeld, Anne E.
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- 2001
11. Sociodemographic and Clinical Factors Associated With Increasing Bacterial Sexually Transmitted Infection Diagnoses in Men Who Have Sex With Men Accessing Care at a Boston Community Health Center (2005–2015)
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Mayer, Kenneth H, Maloney, Kevin M, Levine, Kenneth, King, Dana, Grasso, Chris, Krakower, Douglas S, Rosenberg, Eli S, and Boswell, Stephen L
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- 2017
- Full Text
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12. Multiple Imputation to Account for Measurement Error in Marginal Structural Models
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CNICS, Edwards, Jessie K., Cole, Stephen R., Westreich, Daniel, Crane, Heidi, Eron, Joseph J., Mathews, W. Christopher, Moore, Richard, Boswell, Stephen L., Lesko, Catherine R., and Mugavero, Michael J.
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- 2015
13. Characterizing HIV Transmission Networks Across the United States
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Aldous, Jeannette L., Pond, Sergei Kosakovsky, Poon, Art, Jain, Sonia, Qin, Huifang, Kahn, James S., Kitahata, Mari, Rodriguez, Benigno, Dennis, Ann M., Boswell, Stephen L., Haubrich, Richard, and Smith, Davey M.
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- 2012
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14. Comprehensive Transgender Healthcare: The Gender Affirming Clinical and Public Health Model of Fenway Health
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Reisner, Sari L., Bradford, Judith, Hopwood, Ruben, Gonzalez, Alex, Makadon, Harvey, Todisco, David, Cavanaugh, Timothy, VanDerwarker, Rodney, Grasso, Chris, Zaslow, Shayne, Boswell, Stephen L., and Mayer, Kenneth
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- 2015
- Full Text
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15. Antiretroviral Preexposure Prophylaxis: Opportunities and Challenges for Primary Care Physicians
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Mayer, Kenneth H., Krakower, Douglas S., and Boswell, Stephen L.
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- 2016
- Full Text
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16. The Ryan White HIV/AIDS Program in the Age of Health Care Reform
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Cahill, Sean R, Mayer, Kenneth H, and Boswell, Stephen L
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- 2015
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17. Improved CD4 Lymphocyte Outgrowth in Response to Effective Antiretroviral Therapy
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Merrill, Debra P., Martinez-Picado, Javier, Tremblay, Cécile, Sax, Paul E., Boswell, Stephen L., Wong, Johnson T., D'Aquila, Richard T., Walker, Bruce D., and Hirsch, Martin S.
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- 1999
18. Potential Clinical Implications of Interlaboratory Variability in CD4⁺ T-Lymphocyte Counts of Patients Infected with Human Immunodeficiency Virus
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Sax, Paul E., Boswell, Stephen L., and Hirsch, Martin S.
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- 1995
19. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection
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Rodriguez, Benigno, Sethi, Ajay K., Cheruvu, Vinay K., Mackay, Wilma, Bosch, Ronald J., Kitahata, Mari, Boswell, Stephen L., Mathews, W. Christopher, Bangsberg, David R., Martin, Jeffrey, Whalen, Christopher C., Sieg, Scott, Yadavalli, Suhrida, Deeks, Steven G., and Lederman, Michael M.
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CD4 lymphocytes -- Measurement ,HIV infection -- Care and treatment ,RNA -- Synthesis - Abstract
The proportion of variability is estimated in rate of CD4 cell loss predicted by presenting plasma HIV RNA levels in untreated plasma human immunodeficiency virus (HIV)-infected persons. The HIV RNA levels predict the rate of CD4 cell decline only minimally in untreated persons, which have implications for treatment decisions in HIV infection and for understanding the pathogenesis of progressive immune deficiency.
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- 2006
20. Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals
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Caniglia, Ellen C. Robins, James M. Cain, Lauren E. Sabin, Caroline Logan, Roger Abgrall, Sophie Mugavero, Michael J. and Hernandez-Diaz, Sonia Meyer, Laurence Seng, Remonie and Drozd, Daniel R. Seage, III, George R. Bonnet, Fabrice Le Marec, Fabien Moore, Richard D. Reiss, Peter van Sighem, Ard and Mathews, William C. Jarrin, Inma Alejos, Belen Deeks, Steven G. Muga, Roberto Boswell, Stephen L. Ferrer, Elena and Eron, Joseph J. Gill, John Pacheco, Antonio Grinsztejn, Beatriz Napravnik, Sonia Jose, Sophie Phillips, Andrew and Justice, Amy Tate, Janet Bucher, Heiner C. Egger, Matthias and Furrer, Hansjakob Miro, Jose M. Casabona, Jordi Porter, Kholoud Touloumi, Giota Crane, Heidi Costagliola, Dominique and Saag, Michael Hernan, Miguel A.
- Abstract
Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the “no direct effect” assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/mu l compared with 500 cells/mu l and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The “no direct effect” assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.
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- 2019
21. A 38-year-old man with the acquired immunodeficiency syndrome and cavitary pulmonary lesions
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Boswell, Stephen L. and Van Gorder, Mark
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Pneumocystis carinii pneumonia -- Diagnosis ,AIDS patients -- Health aspects - Abstract
A 38-year-old man was admitted to a hospital because of increasing shortness of breath, chest pain and a chronic lung condition. He had been diagnosed with AIDS one year earlier. Even though he had a chronic lung disease, samples of sputum and bronchoalveolar lavage had consistently tested negative for Pneumocystis carinii. This organism is a common cause of lung infection in AIDS patients. During his hospitalization a section of his lung was removed and microscopic examination revealed that he had Pneumocystis carinii infection. This infection is usually much easier to diagnose.
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- 1997
22. Immunologic and Virologic Effects of Subcutaneous Interleukin 2 in Combination With Antiretroviral Therapy: A Randomized Controlled Trial
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Davey, Richard T., Jr, Murphy, Robert L., Graziano, Frank M., Boswell, Stephen L., Pavia, Andrew T., Cancio, Margarita, Nadler, Jeffrey P., Chaitt, Doreen G., Dewar, Robin L., Sahner, David K., Duliege, Anne-Marie, Capra, William B., Leong, Wai-Ping, Giedlin, Martin A., Lane, H. Clifford, and Kahn, James O.
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- 2000
23. The History of Transfusion AIDS: Practice and Policy Alternatives
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Sapolsky, Harvey M., primary and Boswell, Stephen L., additional
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- 1992
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24. Weekly Clinicopathological Exercises: Case 27-1997: A 38-Year-Old Man with the Acquired Immunodeficiency Syndrome and Cavitary Pulmonary Lesions
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Boswell, Stephen L. and van Gorder, Mark
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- 1997
25. Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study
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Caniglia, Ellen C. Cain, Lauren E. Sabin, Caroline A. and Robins, James M. Logan, Roger Abgrall, Sophie Mugavero, Michael J. Hernandez-Diaz, Sonia Meyer, Laurence Seng, Remonie Drozd, Daniel R. Seage, III, George R. Bonnet, Fabrice Dabis, Francois Moore, Richard D. Reiss, Peter and van Sighem, Ard Mathews, William C. del Amo, Julia Moreno, Santiago Deeks, Steven G. Muga, Roberto Boswell, Stephen L. and Ferrer, Elena Eron, Joseph J. Napravnik, Sonia Jose, Sophie Phillips, Andrew Justice, Amy C. Tate, Janet P. and Gill, John Pacheco, Antonio Veloso, Valdilea G. Bucher, Heiner C. Egger, Matthias Furrer, Hansjakob Porter, Kholoud and Touloumi, Giota Crane, Heidi Miro, Jose M. Sterne, Jonathan A. Costagliola, Dominique Saag, Michael Hernan, Miguel A. HIV-CAUSAL Collaboration Ctr AIDS Res Network Integra
- Abstract
Background Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on time-varying CD4 cell counts in virologically suppressed HIV-positive individuals. Methods In this observational study, we used data from prospective studies of HIV-positive individuals in Europe (France, Greece, the Netherlands, Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies that differ in the threshold used to measure CD4 cell count and HIV RNA viral load every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the threshold CD4 counts of 200 cells per mu L, 350 cells per mu L, and 500 cells per mu L. Using inverse probability weighting to adjust for baseline and time-varying confounders, we estimated hazard ratios (HRs) of death and of AIDS-defining illness or death, risk ratios of virological failure, and mean differences in CD4 cell count. Findings 47 635 individuals initiated an antiretroviral therapy regimen between Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in our study. During follow-up, CD4 cell count was measured on average every 4.0 months and viral load every 3.8 months. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1.05 (95% CI 0.86-1.29) for threshold 200 and 1.02 (0.91.1.14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1.08 (0.95-1.22) for threshold 200 and 1.03 (0.96-1.12) for threshold 350. Compared with threshold 500, the 24 month risk ratios of virological failure (viral load more than 200 copies per mL) were 2.01 (1.17-3.43) for threshold 200 and 1.24 (0.89-1.73) for threshold 350, and 24 month mean CD4 cell count differences were 0.4 (-25.5 to 26.3) cells per mu L for threshold 200 and -3.5 (-16.0 to 8.9) cells per mu L for threshold 350. Interpretation Decreasing monitoring to annually when CD4 count is higher than 200 cells per mu L compared with higher than 500 cells per mu L does not worsen the short-term clinical and immunological outcomes of virally suppressed HIV-positive individuals. However, more frequent virological monitoring might be necessary to reduce the risk of virological failure. Further follow-up studies are needed to establish the long-term safety of these strategies.
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- 2017
26. Comparing dynamic monitoring strategies based on evolving CD4 cell counts in virologically suppressed HIV-positive individuals on cART : a prospective observational study in high-income countries
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Caniglia, Ellen C, Cain, Lauren E., Sabin, Caroline A., Robins, James M., Logan, Roger, Abgrall, Sophie, Mugavero, Michael J., Hernández-Díaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R., Seage, George R., Dabis, Francois, Fabrice, Bonnet, Richard, D. Moore, Reiss, Peter, van Sighem, Ard, Mathews, William C., Del Amo, Julia, Moreno, Santiago, Deeks, Steven G., Muga, Roberto, Boswell, Stephen L., Ferrer, Elena, Eron, Joseph J., Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Justice, Amy C., Tate, Janet P., Gill, John, Pacheco, Antonio, Veloso, Valdilea G., Bucher, Heiner C., Egger, Matthias, Furrer, Hansjakob, Kholoud, Porter, Touloumi, Giota, Crane, Heidi, Miró, José M, Sterne, Jonathan A., Dominique, Costagliola, Saag, Michael, and Hernán, Miguel A.
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HIV-RNA ,Monitoring ,CD4 cell count ,Mortality ,Observational studies - Abstract
Altres ajuts: This research was supported by NIH grant R01 AI073127; by NIH grant T32 AI007433 from the National Institute of Allergy and Infectious Diseases; and by the CFAR Network of Integrated Clinical SystemsCNICS, an NIH funded program (R24 AI067039) that was made possible by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Heart, Lung and Blood Institute (NHLBI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Clinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on evolving CD4 cell counts in virologically suppressed HIV-positive individuals. We used data from prospective studies of HIV-positive individuals in Europe and the Americas in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies, which differ with respect to the CD4 cell count threshold that is used to measure CD4 cell count and HIV-RNA every 3-6 months (when below the threshold) or every 9-12 months (when above the threshold). The strategies were defined by the thresholds 200, 350, and 500 cells/μl. We estimated hazard ratios of death and of AIDS-defining illness or death, risk ratios of virologic failure, and mean differences in CD4 cell count using inverse probability weighting to adjust for baseline and time-varying confounders. 47,635 eligible individuals initiated a cART regimen between January, 2000 and November, 2015 and met the eligibility criteria for our study. During follow-up, CD4 cell count and HIV-RNA were measured on average every 4 and 3.8 months, respectively. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1,091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality hazard ratio (95% CI) was 1.05 (0.86, 1.29) for threshold 200 and 1.02 (0.91, 1.14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1.08 (0.95, 1.22) and 1.03 (0.96, 1.12), respectively. The respective 24-month risk ratios (95% CI) of virologic failure (HIV-RNA>200 copies/ml) were 2.01 (1.17, 3.43) and 1.24 (0.89, 1.73) and 24-month mean CD4 cell count differences (95% CIs) were 0.4 (−25.5, 26.3) cells/μl and −3.5 (−16.0, 8.9) cells/μl. Our findings suggest that decreasing monitoring to annually when CD4 cell count>200 cells/μl compared with >500 cells/μl does not worsen the short-term clinical and immunologic outcomes of virologically suppressed HIV-positive individuals, but more frequent virologic monitoring may be necessary to decrease the risk of virologic failure. Further follow-up is needed to establish the long-term safety of these strategies.
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- 2017
27. Aerosol pentamidine prophylaxis following Pneumocystis carinii pneumonia in AIDS patients: results of a blinded dose-comparison study using an ultrasonic nebulizer
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Murphy, Robert L., Lavelle, James P., Allan, J. Davis, Gordin, Fred M., Dupliss, Robert, Boswell, Stephen L., Waskin, Hetty A., Davies, Scott F., Graziano, Frank M., Saag, Michael S., Walter, Jonne B., Crane, Lawrence R., MacDonnell, Keith B., Hodges, Teri L., and Pierce, Phillip F.
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Pentamidine isethionate -- Dosage and administration ,HIV infection -- Complications ,Pneumocystis carinii pneumonia -- Drug therapy ,AIDS (Disease) -- Complications ,Health ,Health care industry - Abstract
PURPOSE: To compare the efficacy and safety of three different doses of prophylactic aerosol Pentamidine in patients with one Prior episode of Pneumocystis carinii pneumonia (PCP) and the acquired immunodeficiency syndrome. PATIENTS AND METHODS: The design of the study was a double-blind, randomized, dose-comparison clinical trial conducted at 13 medical centers within the United States. In stage 1 of the trial, Patients were randomized to receive either 5 mg, 60 mg, or 120 mg of aerosol pentamidine delivered biweekly with the Fisoneb (Fisons, Inc., Rochester, New York) ultrasonic nebulizer. After 24 weeks of therapy, patients entered stage II of the trial, where the 5-mg grOuP was re-randomized to either the 60-mg or 120-mg group. RESULTS: One hundred seventy- five patients entered stage I of the trial and received prophylaxis for a mean of 123.6 days. Seven assigned to the 5-mg biweekly dosing schedule had a confirmed recurrence Of PCP, compared with none in the 60-mg group (p = 0.007) and three in the 120-mg group (p = 0.304). During stage II of the trial, eight patients in the 60-mg group and one additiOnal patient in the 120-mg group had recurrent PCP. After 52 weeks of observation, the likelihood of being PCP-free was 88.0% in the 60-mg group and 93% in the 120-mg group (p= 0.712). Minor adverse events related to aerosol Pentamidine administration included cough, taste perversion, chest Pain, bronchospasm, and dyspnea. These side effects were more common in the 60-mg and 120-mg treatment groups and resulted in withdrawal from the study by one Patient. Serious events were more common after 24 weeks of therapy and included asymptomatic hypoglycemia five), Pancreatitis (two), pneumothorax (one), and extrapulmonary pneumocytosis (one). CONCLUSIONS: These results demonstrate that biweekly administration of 60 mg or 120 mg of aerosol pentamidine significantly decreases PCP recurrence when compared with a 5-mg regimen or findings in historic controls and is generally well tolerated. There is no significant difference in effect or safety between these two dosing regimens in patients followed for at least 52 weeks of therapy., Pneumocystis carinii pneumonia (PCP) was early recognized to occur frequently in AIDS patients. Many times it recurs and often leads to death. The drug pentamidine was found to help prevent such recurrences. Given orally, it was found to cause severe side effects in many patients, so an aerosol method of delivery was developed. This method used a nebulizing (misting) device that gave a continuous flow of the drug. Studies using this method found it to be safe and effective and it is widely used today. Whether it was the best delivery method or whether other aerosol delivery methods might give better results was not studied. Another aerosol delivery method, the Fisons ultrajet nebulizer, was evaluated for prevention of recurrence of pneumonia in AIDS patients. This device is hand held, and delivers the drug on demand rather than in a continuous flow. It also delivers mist particles of a different size than the continuous flow method, which alters distribution of the drug in the lungs. It was tested in 175 AIDS patients who had had one bout of pneumocystis pneumonia. Three dosages were tested: 5 mg, 60 mg, and 120 mg every two weeks. After 24 weeks of treatment, seven patients in the 5 mg group had a relapse of PCP, none in the 60 mg group had a relapse, and three in the 120 mg group had a relapse. The patients in the 5 mg group were reassigned to the other two groups because the early results indicated it was an ineffective dose. The study then continued for another 28 weeks. Final results revealed that 88 percent of the patients receiving the 60 mg dose and 93 percent receiving the 120 mg dose did not have a relapse of PCP. This compares to relapse rates of 60 percent when no treatment is given. Mild side effects occurred in 5 percent of the patients. This aerosol method is both safe and effective. It compares favorably with the more commonly used nebulizer because it uses a lower dose, and the hand-held delivery system is easier to use and will probably cost less. (Consumer Summary produced by Reliance Medical Information, Inc.)
- Published
- 1991
28. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study
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Caniglia, Ellen C. Sabin, Caroline Robins, James M. Logan, Roger Cain, Lauren E. Abgrall, Sophie Mugavero, Michael J. and Hernandez-Diaz, Sonia Meyer, Laurence Seng, Remonie and Drozd, Daniel R. Seage, III, George R. Bonnet, Fabrice and Dabis, Francois Moore, Richard R. Reiss, Peter van Sighem, Ard Mathews, William C. del Amo, Julia Moreno, Santiago and Deeks, Steven G. Muga, Roberto Boswell, Stephen L. Ferrer, Elena Eron, Joseph J. Napravnik, Sonia Jose, Sophie and Phillips, Andrew Olson, Ashley Justice, Amy C. Tate, Janet P. Bucher, Heiner C. Egger, Matthias Touloumi, Giota and Sterne, Jonathan A. Costagliola, Dominique Saag, Michael and Hernan, Miguel A. Ctr AIDS Res Network Integrated
- Abstract
Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 +/- 1 months, (2) 6 +/- 1 months, and (3) 9-12 +/- 1 months. We used inverseprobability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -25.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.
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- 2016
29. Using observational data to emulate a randomized trial of dynamic treatment switching strategies
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van Sighem, Ard, Olson, Ashley, Saag, Michael S., Abgrall, Sophie, Cain, Lauren E., Vandenhende, Marie-Anne, Shepherd, Bryan E., Justice, Amy C., Geng, Elvin H., Ingle, Suzanne M., Jose, Sophie, Kitahata, Mari M., Seng, Rémonie, Bucher, Heiner C., Cozzi-Lepri, Alessandro, Campbell, Colin N.J., Van Rompaey, Stephen E., Vourli, Georgia, del Amo, Julia, Robins, James M., Haubrich, Richard, Mugavero, Michael J., Rybniker, Jan, Antinori, Andrea, Stephan, Christoph, Moore, Richard, Dabis, François, Egger, Matthias, Hernán, Miguel A., Sabin, Caroline A., Boswell, Stephen L., Phillips, Andrew N., Petersen, Maya, D'ArminioMonforte, Antonella, Gill, M. John, Pérez-Hoyos, Santiago, Tate, Janet P., Samji, Hasina, Costagliola, Dominique, Rodríguez, Benigno, Guest, Jodie L., Sterne, Jonathan A.C., Eron, Joseph J., Hogg, Robert S., Reiss, Peter, Meyer, Laurence, Teira, Ramó n, Touloumi, Giota, Casabona, Jordi, Jarrin, Inma, Deeks, Steven G., Logan, Roger, Moreno, Santiago, Napravnik, Sonia, and May, Margaret T.
- Abstract
BACKGROUND: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).METHODS: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.RESULTS: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.CONCLUSIONS: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.
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- 2016
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30. Using observational data to emulate a randomized trial of dynamic treatment-switching strategies: an application to antiretroviral therapy
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Cain, Lauren E. Saag, Michael S. Petersen, Maya May, Margaret T. Ingle, Suzanne M. Logan, Roger Robins, James M. and Abgrall, Sophie Shepherd, Bryan E. Deeks, Steven G. and Gill, M. John Touloumi, Giota Vourli, Georgia Dabis, Francois Vandenhende, Marie-Anne Reiss, Peter van Sighem, Ard Samji, Hasina Hogg, Robert S. Rybniker, Jan Sabin, Caroline A. Jose, Sophie del Amo, Julia Moreno, Santiago and Rodriguez, Benigno Cozzi-Lepri, Alessandro Boswell, Stephen L. and Stephan, Christoph Perez-Hoyos, Santiago Jarrin, Inma and Guest, Jodie L. Monforte, Antonella D'Arminio Antinori, Andrea and Moore, Richard Campbell, Colin N. J. Casabona, Jordi and Meyer, Laurence Seng, Remonie Phillips, Andrew N. Bucher, Heiner C. Egger, Matthias Mugavero, Michael J. Haubrich, Richard Geng, Elvin H. Olson, Ashley Eron, Joseph J. and Napravnik, Sonia Kitahata, Mari M. Van Rompaey, Stephen E. and Teira, Ramon Justice, Amy C. Tate, Janet P. Costagliola, Dominique Sterne, Jonathan A. C. Hernan, Miguel A. and Antiretroviral Therapy Cohort Ctr Aids Res Network Integra and HIV-CAUSAL Collaboration
- Abstract
Background: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual’s time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy). Methods: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting. Results: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death. Conclusions: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses.
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- 2016
31. Emerging models of clinical services for men who have sex with men: focused versus comprehensive approaches
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Mayer, Kenneth H., primary, Vanderwarker, Rodney, additional, Grasso, Chris, additional, and Boswell, Stephen L., additional
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- 2017
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32. Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis
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Kim, H. Nina, primary, Nance, Robin, additional, Van Rompaey, Stephen, additional, Delaney, Joseph C., additional, Crane, Heidi M., additional, Cachay, Edward R., additional, Geng, Elvin, additional, Boswell, Stephen L., additional, Rodriguez, Benigno, additional, Eron, Joseph J., additional, Saag, Michael, additional, Moore, Richard D., additional, and Kitahata, Mari M., additional
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- 2016
- Full Text
- View/download PDF
33. Antiretroviral Preexposure Prophylaxis
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Mayer, Kenneth H., primary, Krakower, Douglas S., additional, and Boswell, Stephen L., additional
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- 2016
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34. Factors Associated With Gaps in Medicaid Enrollment Among People With HIV and the Effect of Gaps on Viral Suppression.
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Monroe, Anne K., Myint, Leslie, Rutstein, Richard M., Aberg, Judith, Boswell, Stephen L., Agwu, Allison L., Gebo, Kelly A., and Moore, Richard D.
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- 2018
- Full Text
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35. Multiple Imputation to Account for Measurement Error in Marginal Structural Models
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Edwards, Jessie K., primary, Cole, Stephen R., additional, Westreich, Daniel, additional, Crane, Heidi, additional, Eron, Joseph J., additional, Mathews, W. Christopher, additional, Moore, Richard, additional, Boswell, Stephen L., additional, Lesko, Catherine R., additional, and Mugavero, Michael J., additional
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- 2015
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- View/download PDF
36. Transmitted Drug Resistance in the CFAR Network of Integrated Clinical Systems Cohort: Prevalence and Effects on Pre-Therapy CD4 and Viral Load
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Poon, Art F. Y., primary, Aldous, Jeannette L., additional, Mathews, W. Christopher, additional, Kitahata, Mari, additional, Kahn, James S., additional, Saag, Michael S., additional, Rodríguez, Benigno, additional, Boswell, Stephen L., additional, Frost, Simon D. W., additional, and Haubrich, Richard H., additional
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- 2011
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37. Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice
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Drozd, Daniel R., Saag, Michael S., Westfall, Andrew O., Mathews, William Chris, Haubrich, Richard, Boswell, Stephen L., Cole, Stephen R., Porter, Donna, Kitahata, Mari M., Juday, Timothy, and Rosenblatt, Lisa
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Observational Study ,ART ,atripla ,comparative effectiveness ,HIV ,single tablet regimen - Abstract
We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. Temporal trends in care may have confounded results.
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- 2017
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38. Case 27-1997
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Boswell, Stephen L., primary and van Gorder, Mark, additional
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- 1997
- Full Text
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39. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study
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Caniglia, Ellen C., Sabin, Caroline, Robins, James M., Logan, Roger, Cain, Lauren E., Abgrall, Sophie, Mugavero, Michael J., Hernandez-Diaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R., Seage, George R., Bonnet, Fabrice, Dabis, Francois, Moore, Richard R., Reiss, Peter, van Sighem, Ard, Mathews, William C., del Amo, Julia, Moreno, Santiago, Deeks, Steven G., Muga, Roberto, Boswell, Stephen L., Ferrer, Elena, Eron, Joseph J., Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Olson, Ashley, Justice, Amy C., Tate, Janet P., Bucher, Heiner C., Egger, Matthias, Touloumi, Giota, Sterne, Jonathan A., Costagliola, Dominique, Saag, Michael, and Hernán, Miguel A.
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HIV ,CD4 cell count ,HIV RNA ,monitoring ,observational studies ,mortality - Abstract
Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9–12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9–12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.
- Published
- 2016
- Full Text
- View/download PDF
40. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study
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Hernán, Miguel A, Justice, Amy C, Del Amo, Julia, Sabin, Caroline, Cain, Lauren E, Reiss, Peter, Abgrall, Sophie, Dabis, Francois, Costagliola, Dominique, Mugavero, Michael J, Drozd, Daniel R, Moore, Richard R, Logan, Roger, Egger, Matthias, Robins, James M, Olson, Ashley, Mathews, William C, Deeks, Steven G, Van Sighem, Ard, Saag, Michael, Bucher, Heiner C, Sterne, Jonathan A, Ferrer, Elena, Hernandez-Diaz, Sonia, Eron, Joseph J, Muga, Roberto, Caniglia, Ellen C, Meyer, Laurence, Jose, Sophie, Touloumi, Giota, Seng, Remonie, Phillips, Andrew, Boswell, Stephen L, Seage, George R, Tate, Janet P, Napravnik, Sonia, Bonnet, Fabrice, and Moreno, Santiago
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610 Medicine & health ,360 Social problems & social services ,3. Good health - Abstract
OBJECTIVE To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). DESIGN Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. METHODS Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. RESULTS In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. CONCLUSIONS Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.
41. Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals
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Caniglia, Ellen C, Robins, James M, Cain, Lauren E, Sabin, Caroline, Logan, Roger, Abgrall, Sophie, Mugavero, Michael J, Hernández-Díaz, Sonia, Meyer, Laurence, Seng, Remonie, Drozd, Daniel R, Seage Iii, George R, Bonnet, Fabrice, Le Marec, Fabien, Moore, Richard D, Reiss, Peter, Van Sighem, Ard, Mathews, William C, Jarrín, Inma, Alejos, Belén, Deeks, Steven G, Muga, Roberto, Boswell, Stephen L, Ferrer, Elena, Eron, Joseph J, Gill, John, Pacheco, Antonio, Grinsztejn, Beatriz, Napravnik, Sonia, Jose, Sophie, Phillips, Andrew, Justice, Amy, Tate, Janet, Bucher, Heiner C, Egger, Matthias, Furrer, Hansjakob, Miro, Jose M, Casabona, Jordi, Porter, Kholoud, Touloumi, Giota, Crane, Heidi, Costagliola, Dominique, Saag, Michael, and Hernán, Miguel A
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610 Medicine & health ,360 Social problems & social services ,3. Good health - Abstract
Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.
42. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study
- Author
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Moore, Richard R., Sterne, Jonathan A., Del Amo, Julia, Justice, Amy C., Hernán, Miguel A., Abgrall, Sophie, Cain, Lauren E., Moreno, Santiago, Ferrer, Elena, Logan, Roger, Mathews, William C., Jose, Sophie, Van Sighem, Ard, Drozd, Daniel R., Dabis, Francois, Egger, Matthias, Tate, Janet P., Hernandez-DIaz, Sonia, Phillips, Andrew, Napravnik, Sonia, Olson, Ashley, Costagliola, Dominique, Touloumi, Giota, Bucher, Heiner C., Sabin, Caroline, Saag, Michael, Muga, Roberto, Meyer, Laurence, Robins, James M., Deeks, Steven G., Seng, Remonie, Bonnet, Fabrice, Seage, George R., Mugavero, Michael J., Reiss, Peter, Eron, Joseph J., Boswell, Stephen L., and Caniglia, Ellen C.
- Subjects
virus diseases ,3. Good health - Abstract
To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART).
43. Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice
- Author
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Rosenblatt, Lisa, Cole, Stephen R., Mathews, William Chris, Westfall, Andrew O., Juday, Timothy, Kitahata, Mari M., Porter, Donna, Saag, Michael S., Boswell, Stephen L., Drozd, Daniel R., and Haubrich, Richard
- Subjects
virus diseases ,3. Good health - Abstract
We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. Temporal trends in care may have confounded results.
44. Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis.
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Kim HN, Nance R, Van Rompaey S, Delaney JC, Crane HM, Cachay ER, Geng E, Boswell SL, Rodriguez B, Eron JJ, Saag M, Moore RD, and Kitahata MM
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- Adult, CD4 Lymphocyte Count, Coinfection complications, Disease Progression, Female, HIV Infections physiopathology, Hepatitis C complications, Hepatitis C physiopathology, Humans, Incidence, Liver Cirrhosis physiopathology, Male, Middle Aged, Prospective Studies, Risk Factors, United States epidemiology, Viral Load, HIV Infections complications, HIV Infections drug therapy, Liver Cirrhosis etiology
- Abstract
Background: Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression., Methods: We determined the incidence and predictors of advanced hepatic fibrosis measured by the Fibrosis-4 index (≥3.25) in a large diverse population of HIV-infected patients without significant liver disease at baseline (Fibrosis-4 score <1.45) in care between January 2000 and March 2014. We used Cox proportional hazards analysis to examine factors associated with progression to Fibrosis-4 score ≥3.25., Results: Among 14,198 HIV-infected patients, hepatitis C virus (HCV) coinfection [adjusted hazard ratio (aHR) 1.9, 95% confidence interval (CI): 1.6 to 2.1], hepatitis B virus coinfection (aHR 1.5, 95% CI: 1.2 to 1.8), alcohol-use disorder (aHR 1.4, 95% CI: 1.2 to 1.6), and diabetes (aHR 1.9, 95% CI: 1.6 to 2.3) were associated with progression to advanced fibrosis in multivariable analysis. In addition, patients at each lower level of time-varying CD4 cell count had a significantly greater risk of progression, with ∼7-fold higher risk in those with CD4 <100 cells per cubic millimeter (aHR 6.9, 95% CI: 5.8 to 8.3) compared with CD4 ≥500 cells per cubic millimeter. An increasing gradient of risk was also observed among patients with higher time-varying HIV viral load (VL), with the greatest risk noted with VL ≥100,000 copies per milliliter (aHR 2.6, 95% CI: 2.2 to 3.1) compared with VL <500 copies per milliliter., Conclusions: Lower CD4 cell count and higher HIV VL were significantly associated with progression to advanced hepatic fibrosis in a dose-dependent manner, independent of the risk associated with traditional factors: hepatitis C virus or hepatitis B virus coinfection, alcohol, and diabetes. Our findings suggest that early treatment of HIV infection could mitigate liver disease.
- Published
- 2016
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- View/download PDF
45. High levels of antiretroviral use and viral suppression among persons in HIV care in the United States, 2010.
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Dombrowski JC, Kitahata MM, Van Rompaey SE, Crane HM, Mugavero MJ, Eron JJ, Boswell SL, Rodriguez B, Mathews WC, Martin JN, Moore RD, and Golden MR
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- Adolescent, Adult, CD4 Lymphocyte Count, Cross-Sectional Studies, Drug Administration Schedule, Female, HIV drug effects, HIV Infections immunology, Humans, Male, Middle Aged, RNA, Viral blood, United States, Viral Load, Young Adult, Anti-HIV Agents therapeutic use, HIV physiology, HIV Infections drug therapy, HIV Infections virology
- Abstract
Background: Contemporary data on patterns of antiretroviral therapy (ART) use in the United States are needed to inform efforts to improve the HIV care cascade., Methods: We conducted a cross-sectional study of patients in the Centers for AIDS Research Network of Integrated Clinical Systems cohort who were in HIV care in 2010 to assess ART use and outcomes, stratified by nadir CD4 count (≤350, 351-500, or >500 cells/mm), demographics, psychiatric diagnoses, substance use, and engagement in continuous care (≥2 visits ≥3 months apart in 2010)., Results: Of 8633 patients at 7 sites who had ≥1 medical visit and ≥1 viral load in 2010, 94% had ever initiated ART, 89% were on ART, and 70% had an undetectable viral load at the end of 2010. Fifty percent of ART-naive patients had nadir CD4 counts >500 cells per cubic millimeter, but this group comprised just 3% of the total population. Among patients who were ART naive at the time of cohort entry (N = 4637), both ART initiation and viral suppression were strongly associated with nadir CD4 count. Comparing 2009 and 2010, the percentages of patients with viral suppression among those with nadir CD4 counts 351-500 and >500 cells per cubic millimeter were 44% vs. 57% and 25% vs. 33%, respectively. Engagement in care was the only factor consistently associated with ART use and viral suppression across nadir CD4 count strata., Conclusions: Our findings suggest that ART use and viral suppression among persons in HIV care may be more common than estimated in some previous studies and increased from 2009 to 2010.
- Published
- 2013
- Full Text
- View/download PDF
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