Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

First occurrence of diabetes, chronic kidney disease, and hypertension among North American HIV-infected adults, 2000-2013

Background: There remains concern regarding the occurrence of noncommunicable diseases (NCDs) among individuals aging with human immunodeficiency virus (HIV), but few studies have described whether disparities between demographic subgroups are present among individuals on antiretroviral therapy (ART) with access to care. Methods: We assessed the first documented occurrence of type 2 diabetes mellitus (DM), chronic kidney disease (CKD), and treated hypertension (HTN) by age, sex, and race within the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). HIV-infected adults (≥18 years) who initiated ART were observed for first NCD occurrence between 1 January 2000 and 31 December 2013. Cumulative incidences as of age 70 were estimated accounting for the competing risk of death; Poisson regression was used to compare rates of NCD occurrence by demographic subgroup. Results: We included >50000 persons with >250000 person-years of follow-up. Median follow-up was 4.7 (interquartile range, 2.4–8.1) years. Rates of first occurrence (per 100 person-years) were 1.2 for DM, 0.6 for CKD, and 2.6 for HTN. Relative to non-black women, the cumulative incidences were increased in black women (68% vs 51% for HTN, 52% vs 41% for DM, and 38% vs 35% for CKD; all P < .001); this disparity was also found among men (73% vs 60% for HTN, 44% vs 34% for DM, and 30% vs 25% for CKD; all P < .001). Conclusions: Racial disparities in the occurrence of DM, CKD, and HTN emphasize the need for prevention and treatment options for these HIV populations receiving care in North America

End-Stage Renal Disease Among HIV-Infected Adults in North America

Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks

The Epidemiology of Age-Associated Conditions Among Individuals Living with HIV in North America

Background: Individuals receiving antiretroviral therapy (ART) for their HIV infection are getting older, but optimal management of care is complicated by the development of age-associated comorbidities. The goals of this dissertation are to examine the development of age-associated comorbidities as well as disparities in their occurrence, and assess the changing prevalence of their co-occurrence by demographics, route of HIV acquisition, and geographic residence, using data within 2000-2013. Methods: We analyzed data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We estimated rates of first occurrence for hypertension, diabetes, and chronic kidney disease by demographic subgroup using Poisson regression methods. Cumulative incidences by age 70 were estimated for each outcome, accounting for the competing risk of death using the Fine and Gray method. Trends and disparities in the prevalence of multimorbidity, defined as the co-occurrence of ≥2 age-associated conditions (inclusive of: hypertension, diabetes, chronic kidney disease, hypercholesterolemia, end-stage renal disease, and non-AIDS-related malignancies), were assessed by logistic and Poisson regression with robust variance, respectively, using generalized estimating equations to adjust for within person correlation over time. Results: We identified significant disparities in the occurrence of hypertension, diabetes, and chronic kidney disease between black and non-black men and women, even after adjusting for individual-level characteristics. Rates of first occurrence (per 100 person-years) were: 2.6 (hypertension), 1.2 (diabetes), and 0.6 (chronic kidney disease). Multimorbidity prevalence increased from 8.2% in 2000 to 22.4% in 2009 (ptrend<0.001) and the most commonly occurring conditions were hypertension and hypercholesterolemia. Adjusting for age, sex, race, HIV risk, year, other HIV-related variables, individuals residing in the South (aPR=1.55 [1.30,1.85]) and the West (aPR=1.33 [1.11,1.60]) relative to the Northeast were more likely to have multimorbidity. There was no difference by sex and blacks were less likely to have multimorbidity (compared to whites, aPR=0.86 [0.75,0.98]). Conclusions: In a population with equal access to clinical care and ART, disparities between sex and race persist, and the rise in the prevalence of multimorbidity is likely to continue. The increase in the number of patients who will require complicated care plans will require evidence-based strategies to improve their health outcomes

The Epidemiology of Age-Associated Conditions Among Individuals Living with HIV in North America

Background: Individuals receiving antiretroviral therapy (ART) for their HIV infection are getting older, but optimal management of care is complicated by the development of age-associated comorbidities. The goals of this dissertation are to examine the development of age-associated comorbidities as well as disparities in their occurrence, and assess the changing prevalence of their co-occurrence by demographics, route of HIV acquisition, and geographic residence, using data within 2000-2013. Methods: We analyzed data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We estimated rates of first occurrence for hypertension, diabetes, and chronic kidney disease by demographic subgroup using Poisson regression methods. Cumulative incidences by age 70 were estimated for each outcome, accounting for the competing risk of death using the Fine and Gray method. Trends and disparities in the prevalence of multimorbidity, defined as the co-occurrence of ≥2 age-associated conditions (inclusive of: hypertension, diabetes, chronic kidney disease, hypercholesterolemia, end-stage renal disease, and non-AIDS-related malignancies), were assessed by logistic and Poisson regression with robust variance, respectively, using generalized estimating equations to adjust for within person correlation over time. Results: We identified significant disparities in the occurrence of hypertension, diabetes, and chronic kidney disease between black and non-black men and women, even after adjusting for individual-level characteristics. Rates of first occurrence (per 100 person-years) were: 2.6 (hypertension), 1.2 (diabetes), and 0.6 (chronic kidney disease). Multimorbidity prevalence increased from 8.2% in 2000 to 22.4% in 2009 (ptrend<0.001) and the most commonly occurring conditions were hypertension and hypercholesterolemia. Adjusting for age, sex, race, HIV risk, year, other HIV-related variables, individuals residing in the South (aPR=1.55 [1.30,1.85]) and the West (aPR=1.33 [1.11,1.60]) relative to the Northeast were more likely to have multimorbidity. There was no difference by sex and blacks were less likely to have multimorbidity (compared to whites, aPR=0.86 [0.75,0.98]). Conclusions: In a population with equal access to clinical care and ART, disparities between sex and race persist, and the rise in the prevalence of multimorbidity is likely to continue. The increase in the number of patients who will require complicated care plans will require evidence-based strategies to improve their health outcomes

Mind the gap: observation windows to define periods of event ascertainment as a quality control method for longitudinal electronic health record data.

PurposeUse of electronic health records (EHRs) in health research may lead to the false assumption of complete event ascertainment. We estimated "observation windows" (OWs), defined as periods within which the assumption of complete ascertainment of events is more likely to hold, as a quality control approach to reducing the likelihood of this false assumption. We demonstrated the impact of OWs on estimating the rates of type II diabetes mellitus (diabetes) from HIV clinical cohorts.MethodsData contributed by 16 HIV clinical cohorts to the NA-ACCORD were used to identify and evaluate OWs for an operationalized definition of diabetes occurrence as a case study. Procedures included (1) gathering cohort-level data; (2) visualizing and summarizing gaps in observations; (3) systematically establishing start and stop dates during which the assumption of complete ascertainment of diabetes events was reasonable; and (4) visualizing the diabetes OWs relative to the cohort open and close dates to&nbsp;identify immortal person-time. We estimated diabetes occurrence event rates and 95% confidence intervals in the most recent decade that data were available (January 1, 2007, to December 31, 2016).ResultsThe number of diabetes events decreased by 17% with the use of the diabetes OWs; immortal person-time was removed decreasing total person-years by 23%. Consequently, the diabetes rate increased from 1.23 (95% confidence interval [1.20, 1.25]) per 100 person-years to 1.32 [1.29, 1.35] per 100 person-years with the use of diabetes OWs.ConclusionsAs the use of EHR-curated data for event-driven health research continues to expand, OWs have utility as a quality control approach to complete event ascertainment, helping to improve accuracy of estimates by removing immortal person-time when ascertainment is incomplete

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with &gt;10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of &gt;10% body weight increase at two years (adjusted odds ratio&nbsp;=&nbsp;1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

Increased Risk of Myocardial Infarction in HIV-Infected Individuals in North America Compared With the General Population.

BackgroundPrevious studies of cardiovascular disease (CVD) among HIV-infected individuals have been limited by the inability to validate and differentiate atherosclerotic type 1 myocardial infarctions (T1MIs) from other events. We sought to define the incidence of T1MIs and risk attributable to traditional and HIV-specific factors among participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and compare adjusted incidence rates (IRs) to the general population Atherosclerosis Risk in Communities (ARIC) cohort.MethodsWe ascertained and adjudicated incident MIs among individuals enrolled in 7 NA-ACCORD cohorts between 1995 and 2014. We calculated IRs, adjusted incidence rate ratios (aIRRs), and 95% confidence intervals of risk factors for T1MI using Poisson regression. We compared aIRRs of T1MIs in NA-ACCORD with those from ARIC.ResultsAmong 29,169 HIV-infected individuals, the IR for T1MIs was 2.57 (2.30 to 2.86) per 1000 person-years, and the aIRR was significantly higher compared with participants in ARIC [1.30 (1.09 to 1.56)]. In multivariable analysis restricted to HIV-infected individuals and including traditional CVD risk factors, the rate of T1MI increased with decreasing CD4 count [≥500 cells/μL: ref; 350-499 cells/μL: aIRR = 1.32 (0.98 to 1.77); 200-349 cells/μL: aIRR = 1.37 (1.01 to 1.86); 100-199 cells/μL: aIRR = 1.60 (1.09 to 2.34); &lt;100 cells/μL: aIRR = 2.19 (1.44 to 3.33)]. Risk associated with detectable HIV RNA [&lt;400 copies/mL: ref; ≥400 copies/mL: aIRR = 1.36 (1.06 to 1.75)] was significantly increased only when CD4 was excluded.ConclusionsThe higher incidence of T1MI in HIV-infected individuals and increased risk associated with lower CD4 count and detectable HIV RNA suggest that early suppressive antiretroviral treatment and aggressive management of traditional CVD risk factors are necessary to maximally reduce MI risk

On the kinetic barriers of graphene homo-epitaxy

© 2014 AIP Publishing LLC. The diffusion processes and kinetic barriers of individual carbon adatoms and clusters on graphene surfaces are investigated to provide fundamental understanding of the physics governing epitaxial growth of multilayer graphene. It is found that individual carbon adatoms form bonds with the underlying graphene whereas the interaction between graphene and carbon clusters, consisting of 6 atoms or more, is very weak being van der Waals in nature. Therefore, small carbon clusters are quite mobile on the graphene surfaces and the diffusion barrier is negligibly small (∼6 meV). This suggests the feasibility of high-quality graphene epitaxial growth at very low growth temperatures with small carbon clusters (e.g., hexagons) as carbon source. We propose that the growth mode is totally different from 3-dimensional bulk materials with the surface mobility of carbon hexagons being the highest over graphene surfaces that gradually decreases with further increase in cluster size