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1.  Estimation of the Standardized Risk Difference and Ratio in a Competing Risks Framework: Application to Injection Drug Use and Progression to AIDS After Initiation of Antiretroviral Therapy 
American Journal of Epidemiology  2014;181(4):238-245.
There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS.
doi:10.1093/aje/kwu122
PMCID: PMC4325676  PMID: 24966220
AIDS; cohort study; competing risks; HIV; survival function
2.  Trends and Disparities in Antiretroviral Therapy Initiation and Virologic Suppression Among Newly Treatment-Eligible HIV-Infected Individuals in North America, 2001–2009 
Hanna, David B. | Buchacz, Kate | Gebo, Kelly A. | Hessol, Nancy A. | Horberg, Michael A. | Jacobson, Lisa P. | Kirk, Gregory D. | Kitahata, Mari M. | Korthuis, P. Todd | Moore, Richard D. | Napravnik, Sonia | Patel, Pragna | Silverberg, Michael J. | Sterling, Timothy R. | Willig, James H. | Lau, Bryan | Althoff, Keri N. | Crane, Heidi M. | Collier, Ann C. | Samji, Hasina | Thorne, Jennifer E. | Gill, M. John | Klein, Marina B. | Martin, Jeffrey N. | Rodriguez, Benigno | Rourke, Sean B. | Gange, Stephen J. | Benson, A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Ken | Hogg, Robert S. | Harrigan, Richard | Montaner, Julio | Cescon, Angela | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | Rachlis, Anita R. | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M. John | Deeks, Steven G. | Martin, Jeffrey N. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Kitahata, Mari M. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Platt, Aaron | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Webster, Eric | Morton, Liz | Simon, Brenda | Gange, Stephen J. | Abraham, Alison G. | Lau, Bryan | Althoff, Keri N. | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
In the last decade, timely initiation of antiretroviral therapy and resulting virologic suppression have greatly improved in North America concurrent with the development of better tolerated and more potent regimens, but significant barriers to treatment uptake remain.
Background. Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes.
Methods. We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count <350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non–injection drug abuse, alcohol abuse, and mental illness.
Results. Among 10 692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend < .001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend < .001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P < .001).
Conclusions. In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide.
doi:10.1093/cid/cit003
PMCID: PMC3657490  PMID: 23315317
antiretroviral therapy; healthcare disparities; HIV; time factors; viral load
3.  Laboratory Measures as Proxies for Primary Care Encounters: Implications for Quantifying Clinical Retention Among HIV-Infected Adults in North America 
American Journal of Epidemiology  2015;182(11):952-960.
Because of limitations in the availability of data on primary care encounters, patient retention in human immunodeficiency virus (HIV) care is often estimated using laboratory measurement dates as proxies for clinical encounters, leading to possible outcome misclassification. This study included 83,041 HIV-infected adults from 14 clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) who had ≥1 HIV primary care encounters during 2000–2010, contributing 468,816 person-years of follow-up. Encounter-based retention (REB) was defined as ≥2 encounters in a calendar year, ≥90 days apart. Laboratory-based retention (RLB) was defined similarly, using the dates of CD4-positive cell counts or HIV-1 RNA measurements. Percentage of agreement and the κ statistic were used to characterize agreement between RLB and REB. Logistic regression with generalized estimating equations and stabilized inverse-probability-of-selection weights was used to elucidate temporal trends and the discriminatory power of RLB as a predictor of REB, accounting for age, sex, race/ethnicity, primary HIV risk factor, and cohort site as potential confounders. Both REB and RLB increased from 2000 to 2010 (from 67% to 78% and from 65% to 77%, respectively), though REB was higher than RLB throughout (P < 0.01). RLB agreed well with REB (80%–86% agreement; κ = 0.55–0.62, P < 0.01) and had a strong, imperfect ability to discriminate between persons retained and not retained in care by REB (C statistic: C = 0.81, P < 0.05). As a proxy for REB, RLB had a sensitivity and specificity of 84% and 77%, respectively, with misclassification error of 18%.
doi:10.1093/aje/kwv181
PMCID: PMC4655744  PMID: 26578717
clinical encounters; clinical retention; HIV; laboratory measurements; measurement error; misclassification; proxies
4.  Antiretroviral Therapy Use, Medication Adherence, and Viral Suppression among PLWHA with Panic Symptoms 
AIDS and behavior  2015;19(11):2049-2056.
Panic symptoms are prevalent among PLWHAs, yet few studies have examined their relationship with HIV outcomes. Using data from an observational cohort study in Baltimore, MD, we examined the association between panic symptoms and ART use, medication adherence, and viral suppression. Data were analyzed using GEE and adjusted for age, sex, race/ethnicity, cocaine and/or heroin use, clinic enrollment time, alcohol use, and depressive symptoms. Between June 2010 and September 2012, 1195 individuals participated in 2080 audio computer assisted interviews; 9.9% (n=118) of individuals endorsed current panic symptoms. In multivariate analysis, panic symptoms were associated with decreased ART use (IRR 0.94; p = 0.05). Panic symptoms were neither associated with medication adherence nor viral suppression. These findings were independent of depressive symptoms and substance use. Panic symptoms are under-recognized in primary care settings and present an important barrier to ART use. Further studies investigating the reasons for this association are needed.
doi:10.1007/s10461-015-1064-4
PMCID: PMC4712641  PMID: 25903506
5.  Brief Intervention Decreases Drinking Frequency in HIV-Infected, Heavy Drinking Women: Results of a Randomized Controlled Trial 
Objective
Hazardous alcohol use by HIV-infected women is associated with poor HIV outcomes and HIV transmission risk behaviors. We examined the effectiveness of brief alcohol intervention (BI) among hazardous drinking women receiving care in an urban, HIV clinic.
Methods
Women were randomized to a 2-session BI or usual care. Outcomes assessed at baseline, 3, 6 and 12 months included 90-day frequency of any alcohol use and heavy/binge drinking (≥4 drinks per occasion), and average drinks per drinking episode. Secondary outcomes included HIV medication and appointment adherence, HIV1-RNA suppression, and days of unprotected vaginal sex. We examined intervention effectiveness using generalized mixed effect models and quantile regression.
Results
Of 148 eligible women, 74 were randomized to each arm. In mixed effects models, 90-day drinking frequency decreased among intervention group compared to control, with women in the intervention condition less likely to have a drinking day (OR: 0.42 (95% CI: 0.23–0.75). Heavy/binge drinking days and drinks per drinking day did not differ significantly between groups. Quantile regression demonstrated a decrease in drinking frequency in the middle to upper ranges of the distribution of drinking days and heavy/binge drinking days that differed significantly between intervention and control conditions. At follow-up, the intervention group had significantly fewer episodes of unprotected vaginal sex. No intervention effects were observed for other outcomes.
Conclusions
Brief alcohol intervention reduces frequency of alcohol use and unprotected vaginal sex among HIV-infected women. More intensive services may be needed to lower drinks per drinking day and enhance care for more severely affected drinkers.
doi:10.1097/QAI.0000000000000679
PMCID: PMC4634011  PMID: 25967270
Brief Alcohol Intervention; Women; HIV; Alcohol; Randomized Controlled Trial
6.  The Effect of a Multi-Level Intervention on the Initiation of Antiretroviral Therapy (ART) among HIV-Infected Men Who Inject Drugs and Were Diagnosed Late in Thai Nguyen, Vietnam 
PLoS ONE  2016;11(8):e0161718.
Background
In Vietnam, an estimated 256,000 people are living with HIV, and 58% of HIV-infections reported are among people who inject drugs (PWID). While antiretroviral therapy (ART) is widely available in Vietnam, marginalized hard-to-reach male PWID, demonstrate significantly reduced and delayed access to ART.
Methods
We investigated the effect of a randomized four-arm multi-level intervention trial on ART initiation among male PWID. Our analysis was conducted among a subset of trial participants (n = 136), who were newly diagnosed as HIV-infected, treatment naïve, and eligible for ART (baseline late diagnosis). The trial arms included: 1, standard of care (HIV testing and counseling); 2, structural-level intervention (door-to-door communications and community video screenings); 3, individual-level intervention (counseling plus group support); and 4, individual-level plus structural-level intervention. In a time-to-event analysis, we used a non-parametric approach for competing risks to estimate cumulative incidence function (CIF) for ART initiation (event of interest) by arm and the difference in CIF for each trial arm as compared to Arm 1. Follow-up was conducted at 6, 12, 18 and 24 months. Data collection occurred from 2009 to 2013.
Findings
By 24-months, 61.0% initiated ART, and 30.9% had died prior to ART initiation. In the first 6 months, participants in arm 4 (individual plus community intervention) had a 28% (95% confidence interval (CI): 6–50%) increased probability of initiating ART. Despite increasing coverage of ART in all arms throughout follow-up, participants in arm 4 retained a 31% (95% CI: 5–56%) increased probability of initiating ART. The individual and community components of the intervention were only effective when delivered together.
Conclusions
Marginalized, hard-to-reach men, who do not routinely engage in HIV services, and therefore come into care late, may benefit significantly from both individual counseling and group support, in combination with community-focused stigma reduction, when being referred and attempting to initiate urgently needed ART.
doi:10.1371/journal.pone.0161718
PMCID: PMC5007027  PMID: 27579772
7.  Cumulative Incidence of Cancer among HIV-infected Individuals in North America 
Annals of internal medicine  2015;163(7):507-518.
Background
Cancer is increasingly common among HIV patients given improved survival.
Objective
To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status.
Design
Cohort study
Setting
North American AIDS Cohort Collaboration on Research and Design during 1996–2009
Patients
86,620 HIV-infected and 196,987 uninfected adults
Measurements
We estimated cancer-type-specific cumulative incidence by age 75 years by HIV status and calendar era, and examined calendar trends in cumulative incidence and hazard rates.
Results
Cumulative incidences (%) of cancer by age 75 (HIV+/HIV−) were: Kaposi sarcoma (KS), 4.4/0.01; non-Hodgkin’s lymphoma (NHL), 4.5/0.7; lung, 3.4/2.8; anal, 1.5/0.1; colorectal, 1.0/1.5; liver, 1.1/0.4; Hodgkin lymphoma (HL), 0.9/0.1; melanoma, 0.5/0.6; and oral cavity/pharyngeal, 0.8/0.8. Among HIV-infected subjects, we observed decreasing calendar trends in cumulative incidence and hazard rate for KS and NHL. For anal, colorectal and liver cancers, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (−9% per year), allowing greater opportunity to be diagnosed with these cancer types. Despite decreasing hazard rate trends for lung, HL, and melanoma, we did not observe cumulative incidence trends due to the compensating effect of the declining mortality rate on cumulative incidence.
Limitations
Secular trends in screening, smoking, and viral co-infections were not evaluated.
Conclusions
Our analytic approach helped disentangle the effects of improved survival and changing cancer-specific hazard rates on cumulative incidence trends among HIV patients. Cumulative cancer incidence by age 75, approximating lifetime risk in HIV patients, may have clinical utility in this population. The high cumulative incidences by age 75 for KS, NHL, and lung cancer supports early and sustained ART and smoking cessation.
Primary Funding Source
National Institutes of Health
doi:10.7326/M14-2768
PMCID: PMC4711936  PMID: 26436616
8.  End-Stage Renal Disease Among HIV-Infected Adults in North America 
Abraham, Alison G. | Althoff, Keri N. | Jing, Yuezhou | Estrella, Michelle M. | Kitahata, Mari M. | Wester, C. William | Bosch, Ronald J. | Crane, Heidi | Eron, Joseph | Gill, M. John | Horberg, Michael A. | Justice, Amy C. | Klein, Marina | Mayor, Angel M. | Moore, Richard D. | Palella, Frank J. | Parikh, Chirag R. | Silverberg, Michael J. | Golub, Elizabeth T. | Jacobson, Lisa P. | Napravnik, Sonia | Lucas, Gregory M. | Kirk, Gregory D. | Benson, Constance A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Ken | Hogg, Robert S. | Harrigan, Richard | Montaner, Julio | Cescon, Angela | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Moore, Richard D. | Carey, John T. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | Rachlis, Anita R. | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M. John | Deeks, Steven G. | Martin, Jeffrey N. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Althoff, Keri N. | Kitahata, Mari M. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Webster, Eric | Morton, Liz | Simon, Brenda | Gange, Stephen J. | Althoff, Keri N. | Abraham, Alison G. | Lau, Bryan | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
Human immunodeficiency virus-infected individuals have benefited from improved viral suppression, but a discrepancy in end-stage renal disease risk between black and nonblack HIV-infected persons remains, in part due to continued disparities in antiretroviral use and viral suppression, and higher rates of comorbidities.
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.
Methods. Using data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18–80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD.
Results. HIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8–3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9–5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection.
Conclusions. The risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility.
doi:10.1093/cid/ciu919
PMCID: PMC4357817  PMID: 25409471
end-stage renal disease (ESRD); chronic kidney disease (CKD); HIV infection/AIDS; HIV/AIDS; glomerular filtration rate (GFR)
9.  Worth the Weight: Using Inverse Probability Weighted Cox Models in AIDS Research 
AIDS Research and Human Retroviruses  2014;30(12):1170-1177.
Abstract
In an observational study with a time-to-event outcome, the standard analytical approach is the Cox proportional hazards regression model. As an alternative to the standard Cox model, in this article we present a method that uses inverse probability (IP) weights to estimate the effect of a baseline exposure on a time-to-event outcome. IP weighting can be used to adjust for multiple measured confounders of a baseline exposure in order to estimate marginal effects, which compare the distribution of outcomes when the entire population is exposed versus when the entire population is unexposed. For example, IP-weighted Cox models allow for estimation of the marginal hazard ratio and marginal survival curves. IP weights can also be employed to adjust for selection bias due to loss to follow-up. This approach is illustrated using an example that estimates the effect of injection drug use on time until AIDS or death among HIV-infected women.
doi:10.1089/aid.2014.0037
PMCID: PMC4250953  PMID: 25183195
10.  Random survival forests for competing risks 
Biostatistics (Oxford, England)  2014;15(4):757-773.
We introduce a new approach to competing risks using random forests. Our method is fully non-parametric and can be used for selecting event-specific variables and for estimating the cumulative incidence function. We show that the method is highly effective for both prediction and variable selection in high-dimensional problems and in settings such as HIV/AIDS that involve many competing risks.
doi:10.1093/biostatistics/kxu010
PMCID: PMC4173102  PMID: 24728979
AIDS; Brier score; Competing risks; C-index; Cumulative incidence function; Ensemble
11.  Allowing Physicians to Choose the Value of Compensation for Participation in a Web-Based Survey: Randomized Controlled Trial 
Background
Survey response rates among physicians are declining, and determining an appropriate level of compensation to motivate participation poses a major challenge.
Objective
To estimate the effect of permitting intensive care physicians to select their preferred level of compensation for completing a short Web-based survey on physician (1) response rate, (2) survey completion rate, (3) time to response, and (4) time spent completing the survey.
Methods
A total of 1850 US intensivists from an existing database were randomized to receive a survey invitation email with or without an Amazon.com incentive available to the first 100 respondents. The incentive could be instantly redeemed for an amount chosen by the respondent, up to a maximum of US $50.
Results
The overall response rate was 35.90% (630/1755). Among the 35.4% (111/314) of eligible participants choosing the incentive, 80.2% (89/111) selected the maximum value. Among intensivists offered an incentive, the response was 6.0% higher (95% CI 1.5-10.5, P=.01), survey completion was marginally greater (807/859, 94.0% vs 892/991, 90.0%; P=.06), and the median number of days to survey response was shorter (0.8, interquartile range [IQR] 0.2-14.4 vs 6.6, IQR 0.3-22.3; P=.001), with no difference in time spent completing the survey.
Conclusions
Permitting intensive care physicians to determine compensation level for completing a short Web-based survey modestly increased response rate and substantially decreased response time without decreasing the time spent on survey completion.
doi:10.2196/jmir.3898
PMCID: PMC4705363  PMID: 26223821
data collection; monetary incentives; cash; physicians; electronic questionnaire; survey design; response rate
12.  A scenario-based, randomized trial of patient values and functional prognosis on intensivist intent to discuss withdrawing life support 
Critical care medicine  2014;42(6):1455-1462.
Objective
To evaluate the effect of (1) patient values as expressed by family members, and (2) a requirement to document patients’ functional prognosis on intensivists’ intention to discuss withdrawal of life support in a hypothetical family meeting.
Design
A 3-armed, randomized trial
Setting
179 U.S. hospitals with training programs in critical care accredited by the Accreditation Council for Graduate Medical Education
Subjects
630 intensivists recruited via e-mail invitation from a database of 1,850 eligible academic intensivists
Interventions
Each intensivist was randomized to review ten, on-line, clinical scenarios with a range of illness severities involving a hypothetical patient (Mrs. X). In control-group scenarios, the patient did not want continued life support without a reasonable chance of independent living. In the first experimental arm, the patient wanted life support regardless of functional outcome. In the second experimental arm, patient values were identical to the control group, but intensivists were required to record the patient’s estimated three-month functional prognosis
Measurements and Main Results
Response to the question: “Would you bring up the possibility of withdrawing life support with Mrs. X’s family?” answered using a five-point Likert scale. There was no effect of patient values on whether intensivists intended to discuss withdrawal of life support (P = 0.81), but intensivists randomized to record functional prognosis were 49% more likely (95% confidence interval: 20%–85%) to discuss withdrawal.
Conclusions
In this national, scenario-based, randomized trial, patient values had no effect on intensivists’ decisions to discuss withdrawal of life support with family. However, requiring intensivists to record patients’ estimated 3-month functional outcome substantially increased their intention to discuss withdrawal.
doi:10.1097/CCM.0000000000000227
PMCID: PMC4128685  PMID: 24584065
Decision Making; Intensive Care; Resuscitation Orders; Prognosis; Withholding Treatment; Life Support Care
13.  Disparities in the Quality of HIV Care When Using US Department of Health and Human Services Indicators 
Althoff, Keri N. | Rebeiro, Peter | Brooks, John T. | Buchacz, Kate | Gebo, Kelly | Martin, Jeffrey | Hogg, Robert | Thorne, Jennifer E. | Klein, Marina | Gill, M. John | Sterling, Timothy R. | Yehia, Baligh | Silverberg, Michael J. | Crane, Heidi | Justice, Amy C. | Gange, Stephen J. | Moore, Richard | Kitahata, Mari M. | Horberg, Michael A. | Kirk, Gregory D. | Benson, Constance A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Kenneth H. | Hogg, Robert S. | Richard Harrigan, P. | Montaner, Julio SG | Cescon, Angela | Samji, Hasina | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Moore, Richard D. | Carey, John T. | Horberg, Michael A. | Silverberg, Michael J. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann N. | Rachlis, Anita R. | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M.John | Deeks, Steven G. | Martin, Jeffrey N. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Kitahata, Mari M. | Althoff, Keri N. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Morton, Liz | McReynolds, Justin | Lober, William B. | Gange, Stephen J. | Althoff, Keri N. | Abraham, Alison G. | Lau, Bryan | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
We estimated US Department of Health and Human Services (DHHS)–approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ≤200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention- and treatment-related disparities.
doi:10.1093/cid/ciu044
PMCID: PMC3967825  PMID: 24463281
HIV; quality of care; retention in care; antiretroviral therapy; HIV RNA suppression
14.  Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high-risk for HCV and HIV infections 
Journal of acquired immune deficiency syndromes (1999)  2013;64(5):10.1097/QAI.0b013e3182a7ee2e.
Background
HIV and HCV infections may increase interleukin-6 (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory biomarkers, chronic viral infections, clinical factors, and behavioral factors remain poorly understood.
Methods
Using linear regression, we modeled cross-sectional associations between loge IL-6 or loge CRP levels and HCV, HIV, injection drug use, and comorbidity among 1191 injection drug users.
Results
Mean age was 47 years, 46.0% reported currently injecting drugs, 59.0% were HCV-monoinfected, and 27% were HCV/HIV-coinfected. In multivariable models, higher loge IL-6 was associated with HCV monoinfection (β=0.191, 95%CI: 0.043 to 0.339) and HCV/HIV coinfection (β=0.394, 95% CI: 0.214 to 0.574). In contrast, HCV monoinfection (β=−0.523, 95%CI: −0.275 to −0.789) and HCV/HIV coinfection (β=−0.554 95%CI: −0.260 to −0.847) were associated with lower CRP. Lower CRP with HCV infection was independent of liver fibrosis severity, synthetic function, or liver injury markers; CRP decreased with higher HCV RNA. Increased injection intensity was associated with higher IL-6 (p=0.003) and CRP (p<0.001); increasing comorbidity (p<0.001) and older age (p=0.028) were associated with higher IL-6; older age was associated with higher CRP among HCV-uninfected participants (p=0.021).
Conclusion
HIV and HCV infections contribute to chronic inflammation; however, reduced CRP possibly occurs through HCV-virally-mediated mechanisms. Findings highlight potentially modifiable contributors to inflammation.
doi:10.1097/QAI.0b013e3182a7ee2e
PMCID: PMC3848037  PMID: 23978997
inflammation; interleukin-6; C reactive protein; HCV; HIV; injection drug use; comorbidities
15.  Hepatitis C Viremia and the Risk of Chronic Kidney Disease in HIV-Infected Individuals 
Lucas, Gregory M. | Jing, Yuezhou | Sulkowski, Mark | Abraham, Alison G. | Estrella, Michelle M. | Atta, Mohamed G. | Fine, Derek M. | Klein, Marina B. | Silverberg, Michael J. | Gill, M. John | Moore, Richard D. | Gebo, Kelly A. | Sterling, Timothy R. | Butt, Adeel A. | Kirk, Gregory D. | Benson, Constance A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Ken | Hogg, Robert S. | Harrigan, Richard | Montaner, Julio | Cescon, Angela | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Carey, John T. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Horberg, Michael A. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | Rachlis, Anita R. | Rico, Puerto | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M. John | Deeks, Steven G. | Martin, Jeffrey N. | Patel, Pragna | Brooks, John T. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Kitahata, Mari M. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Webster, Eric | Morton, Liz | Simon, Brenda | Gange, Stephen J. | Althoff, Keri N. | Abraham, Alison G. | Lau, Bryan | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
The Journal of Infectious Diseases  2013;208(8):1240-1249.
Background. The role of active hepatitis C virus (HCV) replication in chronic kidney disease (CKD) risk has not been clarified.
Methods. We compared CKD incidence in a large cohort of HIV-infected subjects who were HCV seronegative, HCV viremic (detectable HCV RNA), or HCV aviremic (HCV seropositive, undetectable HCV RNA). Stages 3 and 5 CKD were defined according to standard criteria. Progressive CKD was defined as a sustained 25% glomerular filtration rate (GFR) decrease from baseline to a GFR < 60 mL/min/1.73 m2. We used Cox models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
Results. A total of 52 602 HCV seronegative, 9508 HCV viremic, and 913 HCV aviremic subjects were included. Compared with HCV seronegative subjects, HCV viremic subjects were at increased risk for stage 3 CKD (adjusted HR 1.36 [95% CI, 1.26, 1.46]), stage 5 CKD (1.95 [1.64, 2.31]), and progressive CKD (1.31 [1.19, 1.44]), while HCV aviremic subjects were also at increased risk for stage 3 CKD (1.19 [0.98, 1.45]), stage 5 CKD (1.69 [1.07, 2.65]), and progressive CKD (1.31 [1.02, 1.68]).
Conclusions. Compared with HIV-infected subjects who were HCV seronegative, both HCV viremic and HCV aviremic individuals were at increased risk for moderate and advanced CKD.
doi:10.1093/infdis/jit373
PMCID: PMC3778973  PMID: 23904290
HIV; hepatitis C virus; chronic kidney disease; hepatitis C RNA; cohort study; glomerular filtration rate; injection drug use
16.  Age and decisions to limit life support for patients with acute lung injury: a prospective cohort study 
Critical Care  2014;18(3):R107.
Introduction
The proportion of elderly Americans admitted to the intensive care unit (ICU) in the last month of life is rising. Hence, challenging decisions regarding the appropriate use of life support are increasingly common. The objective of this study was to estimate the association between patient age and the rate of new limitations in the use of life support, independent of daily organ dysfunction status, following acute lung injury (ALI) onset.
Methods
This was a prospective cohort study of 490 consecutive patients without any limitations in life support at the onset of ALI. Patients were recruited from 11 ICUs at three teaching hospitals in Baltimore, Maryland, USA, and monitored for the incidence of six pre-defined limitations in life support, with adjustment for baseline comorbidity and functional status, duration of hospitalization before ALI onset, ICU severity of illness, and daily ICU organ dysfunction score.
Results
The median patient age was 52 (range: 18 to 96), with 192 (39%) having a new limitation in life support in the ICU. Of patients with a new limitation, 113 (59%) had life support withdrawn and died, 53 (28%) died without resuscitation, and 26 (14%) survived to ICU discharge. Each ten-year increase in patient age was independently associated with a 24% increase in the rate of limitations in life support (Relative Hazard 1.24; 95% CI 1.11 to 1.40) after adjusting for daily ICU organ dysfunction score and all other covariates.
Conclusions
Older critically ill patients are more likely to have new limitations in life support independent of their baseline status, ICU-related severity of illness, and daily organ dysfunction status. Future studies are required to determine whether this association is a result of differences in patient preferences by age, or differences in the treatment options discussed with the families of older versus younger patients.
doi:10.1186/cc13890
PMCID: PMC4075260  PMID: 24886945
17.  HIV Viremia and T-Cell Activation Differentially Affect the Performance of Glomerular Filtration Rate Equations Based on Creatinine and Cystatin C 
PLoS ONE  2013;8(12):e82028.
Background
Serum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established.
Methods
We assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFRcr), cystatin C (eGFRcys) and both biomarkers combined (eGFRcr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry.
Results
The median mGFR was >100 ml/min/1.73 m2 in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFRcr-cys being the most accurate overall. In the HIV-positive group, eGFRcys was significantly less accurate and more biased than eGFRcr and eGFRcr_cys. Additionally eGFRcys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFRcys bias in both HIV-positive and HIV-negative groups. In contrast, eGFRcr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C.
Conclusions
The performance of eGFRcys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population.
doi:10.1371/journal.pone.0082028
PMCID: PMC3871673  PMID: 24376511
18.  Alcohol Consumption and CD4 T-cell count response among persons initiating antiretroviral therapy 
Background
We evaluated the longitudinal association of alcohol use with immunological response to combination antiretroviral therapy (ART) among HIV infected individuals.
Methods
This was a prospective cohort study of individuals initiating ART. Participants underwent an Audio Computer-Assisted Self Interview querying drug and alcohol use within 6 months of treatment. Immunological response to ART was defined by CD4 T-cell count (CD4). Primary independent variables were self-reported number of drinks consumed per drinking day (quantity) and days of alcohol consumption in a typical week (frequency). We used linear mixed effects models to quantify the association between CD4 T-cell count and alcohol quantity and frequency and Cox proportional hazards models to estimate the relative hazard of an increase 100, 150 and 200 CD4 cells/mm3 per additional drink per drinking day. Analyses were stratified by gender. Viral suppression was examined as a time-varying covariate.
Results
Between 2000-2008, 1107 individuals were eligible for inclusion in this study. There was no statistically significant difference in CD4 T-cell count by average drinks per drinking day at any frequency of alcohol use irrespective of gender or viral suppression. Similarly, we found no difference in the hazard ratio for drinks per drinking day within the categories of drinking frequency for time to CD4 T-cell count increase of 100, 150 and 200 cells/mm3, respectively.
Conclusions
Among individuals initiating antiretroviral therapy (ART) the benefits of therapy and viral suppression on the immune system outweigh detrimental effects of alcohol, reinforcing the importance of initiating ART and ensuring adequate adherence to therapy.
doi:10.1097/QAI.0b013e3182712d39
PMCID: PMC3541505  PMID: 22955054
HIV; alcohol; Immune Response; CD4 T-CELL COUNT; antiretroviral therapy
20.  Insurance Status, not Race, is Associated with Mortality After an Acute Cardiovascular Event in Maryland 
Journal of General Internal Medicine  2012;27(10):1368-1376.
ABSTRACT
BACKGROUND
It is unclear how lack of health insurance or otherwise being underinsured contributes to observed racial disparities in health outcomes related to cardiovascular disease.
OBJECTIVE
To determine the relative risk of death associated with insurance and race after hospital admission for an acute cardiovascular event.
DESIGN
Prospective cohort study in three hospitals in Maryland representing different demographics between 1993 and 2007.
PATIENTS
Patients with an incident admission who were either white or black, and had either private insurance, state-based insurance or were uninsured. 4,908 patients were diagnosed with acute myocardial infarction, 6,759 with coronary atherosclerosis, and 1,293 with stroke.
MAIN MEASURES
Demographic and clinical patient-level data were collected from an administrative billing database and neighborhood household income was collected from the 2000 US Census. The outcome of all-cause mortality was collected from the Social Security Death Master File.
KEY RESULTS
In an analysis adjusted for race, disease severity, location, neighborhood household income among other confounders, being underinsured was associated with an increased risk of death after myocardial infarction (relative hazard, 1.31 [95 % CI: 1.09, 1.59]), coronary atherosclerosis (relative hazard, 1.50 [95 % CI: 1.26, 1.80]) or stroke (relative hazard, 1.25 [95 % CI: 0.91, 1.72]). Black race was not associated with an increased risk of death after myocardial infarction (relative hazard, 1.03 [95 % CI: 0.85, 1.24]), or after stroke (relative hazard, 1.18 [95 % CI: 0.86, 1.61]) and was associated with a decreased risk of death after coronary atherosclerosis (relative hazard, 0.82 [95 % CI: 0.69, 0.98]).
CONCLUSIONS
Race was not associated with an increased risk of death, before or after adjustment. Being underinsured was strongly associated with death among those admitted with myocardial infarction, or a coronary atherosclerosis event. Our results support growing evidence implicating insurance status and socioeconomic factors as important drivers of health disparities, and potentially racial disparities.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2147-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s11606-012-2147-9
PMCID: PMC3445670  PMID: 22821570
health disparities; insurance coverage; socioeconomic status; race; cardiovascular disease
21.  Changes in sexual and drug-related risk behavior following antiretroviral therapy initiation among HIV-infected injection drug users 
AIDS (London, England)  2012;26(18):2383-2391.
Objective
To evaluate whether HAART is associated with subsequent sexual and drug-related risk behavior compensation among injection drug users (IDUs).
Design
A community-based cohort study of 362 HIV-infected IDUs initiating HAART in Baltimore, Maryland.
Methods
HAART use and risk behavior was assessed at 8316 biannual study visits (median 23). Using logistic regression with generalized estimating equations (GEE), we examined the effect of HAART initiation on changes in risk behavior while adjusting for sociodemographics, alcohol use, CD4+ cell count, year of initiation and consistency of HAART use.
Results
At HAART initiation, participants were a median of 44.4 years old, 71.3% men and 95.3% African–American. In multivariable analysis, HAART initiation was associated with a 75% reduction in the likelihood of unprotected sex [adjusted odds ratio (aOR) 0.25; 95% confidence interval (CI), 0.19–0.32] despite no change in overall sexual activity (aOR 0.95; 0.80–1.12). Odds of any injecting decreased by 38% (aOR 0.62; 0.51–0.75) after HAART initiation. Among the subset of persistent injectors, needle-sharing increased nearly two-fold (aOR 1.99; 1.57–2.52). Behavioral changes were sustained for more than 5 years after HAART initiation and did not differ by consistency of HAART use. Reporting specific high-risk behaviors in the year prior to initiation was a robust predictor of engaging in those behaviors subsequent to HAART.
Conclusion
Overall, substantial declines in sexual risk-taking and active injecting argue against significant behavioral compensation among IDUs following HAART initiation. These data also provide evidence to support identifying persons with risky pre-HAART behavior for targeted behavioral intervention.
doi:10.1097/QAD.0b013e32835ad438
PMCID: PMC3678983  PMID: 23079804
antiretroviral therapy; HIV prevention; injecting; injection drug users; risk compensation; sexual behavior
22.  Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America 
In a large North American cohort study, anal cancer incidence rates were substantially higher for HIV-infected men who have sex with men, other men, and women compared with HIV-uninfected individuals. Rates increased from 1996–1999 to 2000–2003 but plateaued by 2004–2007.
Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends.
Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men).
Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7–151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5–61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8–6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5–2.2). In comparison with the period 2000–2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3–.9) in 1996–1999 and 0.9 (95% CI, .6–1.2) in 2004–2007.
Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
doi:10.1093/cid/cir1012
PMCID: PMC3297645  PMID: 22291097
23.  Impact of Bariatric Surgery on Healthcare Utilization and Costs among Patients with Diabetes 
Medical care  2012;50(1):58-65.
Background
The effect of bariatric surgery on health care utilization and costs among individuals with type 2 diabetes remains unclear.
Objective
To examine healthcare utilization and costs in an insured cohort of individuals with type 2 diabetes after bariatric surgery.
Research Design
Cohort study derived from administrative data from 2002–2008 from 7 Blue Cross Blue Shield Plans.
Subjects
7,806 individuals with type 2 diabetes who had bariatric surgery
Measures
Cost (inpatient, outpatient, pharmacy, other) and utilization (number of inpatient days, outpatient visits, specialist visits).
Results
Compared to pre-surgical costs, the ratio of hospital costs (excluding the initial surgery), among beneficiaries who had any hospital costs, was higher in years 2 through 6 of the post-surgery period and increased over time [post 1: OR = 0.58 (95% CI: 0.50, 0.67); post 6: OR = 3.43 (95% CI: 2.60, 4.53)]. In comparison to the pre-surgical period, the odds of having any healthcare costs was lower in the post-surgery period and remained relatively flat over time. Among those with hospitalizations, the adjusted ratio of inpatient days was higher after surgery [post 1: OR = 1.05 (95% CI: 0.94, 1.16); post 6: OR = 2.77 (95% CI: 1.57, 4.90)]. Among those with primary care visits, the adjusted odds ratio was lower after surgery [post 1: OR = 0.80 (95% CI: 0.78, 0.82); post 6: OR = 0.66 (95% CI: 0.57, 0.76)].
Conclusion
In the six years following surgery, individuals with type 2 diabetes did not have lower healthcare costs than before surgery.
doi:10.1097/MLR.0b013e3182290349
PMCID: PMC3241012  PMID: 22167064
24.  Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care 
AIDS (London, England)  2012;26(15):1907-1915.
Objective
To examine long-term effects of antiretroviral therapy (ART) on kidney function, we evaluated the incidence and risk factors for chronic kidney disease (CKD) among ART-naive, HIV-infected adults and compared changes in estimated glomerular filtration rates (eGFR) before and after starting ART.
Methods
Multicenter observational cohort study of patients with at least one serum creatinine measurement before and after initiating ART. Cox proportional hazard models, and marginal structure models examined CKD risk factors; mixed-effects linear models examined eGFR slopes.
Results
Three thousand, three hundred and twenty-nine patients met entry criteria, contributing 10 099 person-years of observation on ART. ART was associated with a significantly slower rate of eGFR decline (from −2.18 to −1.37 ml/min per 1.73 m2 per year; P = 0.02). The incidence of CKD defined by eGFR thresholds of 60, 45 and 30 ml/min per 1.73 m2 was 10.5, 3.4 and 1.6 per 1000 person-years, respectively. In adjusted analyses black race, hepatitis C coinfection, lower time-varying CD4 cell count and higher time-varying viral load on ART were associated with higher CKD risk, and the magnitude of these risks increased with more severe CKD. Tenofovir and a ritonavir-boosted protease inhibitor (rPI) was also associated with higher CKD risk [hazard odds ratio for an eGFR threshold <60 ml/min per 1.73 m2: 3.35 (95% confidence interval (CI) = 1.40–8.02)], which developed in 5.7% of patients after 4 years of exposure to this regimen-type.
Conclusion
ART was associated with reduced CKD risk in association with CD4 cell restoration and plasma viral load suppression, despite an increased CKD risk that was associated with initial regimens that included tenofovir and rPI.
doi:10.1097/QAD.0b013e328357f5ed
PMCID: PMC3531628  PMID: 22824630
antiretroviral therapy; chronic kidney disease; tenofovir
25.  HIV Infection, Immune Suppression, and Uncontrolled Viremia Are Associated With Increased Multimorbidity Among Aging Injection Drug Users 
Human immunodeficiency virus (HIV)-infected persons, especially those with advanced immune suppression or uncontrolled viremia, experienced increased numbers of multimorbid non-AIDS-defining conditions compared with epidemiologically comparable HIV-uninfected persons. Many of these clinically identified chronic diseases were unrecognized and untreated.
Background. Despite an increasing burden of age-associated non-AIDS outcomes, few studies have investigated the prevalence or correlates of multimorbidity among aging human immunodeficiency virus (HIV)–infected and epidemiologically comparable at-risk populations.
Methods. Among 1262 AIDS Linked to the IntraVenous Experience (ALIVE) study participants followed in a community-based observational cohort, we defined the prevalence of 7 non-AIDS-defining chronic conditions (diabetes, obstructive lung disease, liver disease, anemia, obesity, kidney dysfunction, and hypertension) using clinical and laboratory criteria. Ordinal logistic regression was used to model the odds of increased multimorbidity associated with demographic, behavioral, and clinical factors. Self-reported prevalence was compared with clinically defined prevalence.
Results. Participants were a median of 48.9 years of age; 65.1% were male, 87.5% were African-American, and 28.7% were HIV infected. In multivariable analysis, HIV infection (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.13–1.99) was positively associated with increased multimorbidity. Among HIV-infected participants, multimorbidity was increased with lower nadir CD4 T-cell count (OR, 1.14 per 100-cell decrease; 95% CI, 1.00–1.29) and higher current HIV RNA (OR, 1.32 per log10 increase; 95% CI, 1.08–1.60). Older age, being female, not using cigarettes or drugs, and having depressive symptoms were also associated with increased multimorbidity. A substantial proportion of multimorbid conditions in HIV-infected and HIV-uninfected participants were unrecognized and untreated.
Conclusions. HIV-infected participants experienced increased numbers of multimorbid conditions; risk increased with advanced immunosuppression and higher viremia. These results underscore the heavy burden of multimorbidity associated with HIV and highlight the need for incorporating routine assessment and integrated management of chronic diseases as part of comprehensive healthcare for aging, HIV-infected persons.
doi:10.1093/cid/cir673
PMCID: PMC3214585  PMID: 21976463

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