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1.  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
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.  Hepatic Safety and Tolerability of Raltegravir among HIV Patients Coinfected with Hepatitis B and/or C 
Antiviral therapy  2014;19(4):415-422.
Background
Potential liver toxicity is an important consideration for antiretroviral selection among patients coinfected with HIV and viral hepatitis (B and/or C). We sought to describe the hepatic safety profile of raltegravir in this population.
Methods
Using data from HIV clinical cohorts at Johns Hopkins University and the University of North Carolina at Chapel Hill, we evaluated factors associated with liver enzyme elevations (LEEs) and calculated adverse event incidence rates for patients initiated on raltegravir-containing regimens prior to January 1, 2010. LEEs were graded according to Division of AIDS definitions.
Results
During the study period, 456 patients received raltegravir – of whom 36% were hepatitis-coinfected (138 HCV, 17 HBV, 11 HBV+HCV). Coinfected patients were more likely to have baseline abnormal LEEs, and developed severe (grade 3–4) LEEs at a rate 3.4 times that of HIV-monoinfected patients (95% confidence interval (CI), 1.28, 9.61). Among all participants, the incidence rate for first occurrence of severe LEEs was 5 per 100 person-years (95% CI, 3, 7). In adjusted analyses, coinfected patients had a 2.7-fold increased hazard of severe LEEs (95% CI, 1.03, 7.04). Sixty percent of severe abnormalities occurred within 6 months after starting raltegravir; the drug was discontinued in 3 coinfected patients (1.3%) and 18 monoinfected patients (6.2%).
Conclusions
Compared to HIV-monoinfected patients, those with HIV-hepatitis coinfection are at increased hazard of developing LEEs on raltegravir, at a level similar to other antiretrovirals. Severe events were uncommon, rarely leading to raltegravir discontinuation. With appropriate monitoring, raltegravir-based therapy is safe in hepatitis-coinfected patients.
doi:10.3851/IMP2738
PMCID: PMC4108567  PMID: 24458137
integrase strand transfer inhibitors; hepatotoxicity; clinical cohort; United States
4.  Outcomes of second-line combination antiretroviral therapy for HIV-infected patients: a cohort study from Rio de Janeiro, Brazil 
BMC Infectious Diseases  2014;14(1):699.
Background
World-wide, the notable expansion of HIV/AIDS treatment programs in resource-limited settings has lead to an increasing number of patients in need of second-line cART. To adequately address and prepare for this scenario, critical assessments of the outcomes of second-line cART are particularly relevant in settings where monitoring strategies may be inadequate. We evaluated virologic outcomes of second-line combination antiretroviral therapy (cART) among HIV-infected individuals from Brazil.
Methods
This study was conducted at the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, at Rio de Janeiro, Brazio. For this study we included all patients who started first-line and second-line cART between 2000 and 2013. Second-line cART required a switch in the anchor drug of first-line cART. We evaluated time from second-line start to virologic failure and factors associated with increased risk of failure using multivariable Cox proportional hazards regression models.
Results
Among the 1,311 patients who started first-line cART a total of 386 patients (29.5%) initiated second-line cART, out of which 35.0% and 60.6% switched from their first-line to their second-line cART when their HIV RNA was undetectable and after documented virologic failure, respectively. At second line cART initiation, median age was 38 years [interquartile range (IQR): 31-45years]. Median CD4 count was significantly different for patients starting second-line cART undetectable [412 cells/mm3 (IQR: 240-617)] compared to those starting second-line cART after documented virologic failure [230 cells/mm3 (IQR: 118-322.5)] (p < 0.01). Median time from second-line cART initiation to failure was also significantly different for patients starting second-line cART undetectable compared to those who with documented virologic failure (log-rank test p < 0.01). Multivariable Cox models showed that younger age, lower education, and HIV RNA level were independently associated with an increased hazard of second-line failure among those with documented virologic failure at start of second-line cART.
Conclusions
We have shown that in a middle-income country with universal access to cART, having a detectable HIV RNA at the start of second-line cART as well as younger age and lower education negatively impact second-line outcomes. Our findings could guide HIV treatment efforts as to which strategies would help maximize the durability of these regimens.
doi:10.1186/s12879-014-0699-5
PMCID: PMC4297410  PMID: 25523385
cART; Second-line; Cox proportional hazards regression; HIV/AIDS; Cohort study; Brazil
5.  Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration 
Introduction
HIV care and treatment programmes worldwide are transforming as they push to deliver universal access to essential prevention, care and treatment services to persons living with HIV and their communities. The characteristics and capacity of these HIV programmes affect patient outcomes and quality of care. Despite the importance of ensuring optimal outcomes, few studies have addressed the capacity of HIV programmes to deliver comprehensive care. We sought to describe such capacity in HIV programmes in seven regions worldwide.
Methods
Staff from 128 sites in 41 countries participating in the International epidemiologic Databases to Evaluate AIDS completed a site survey from 2009 to 2010, including sites in the Asia-Pacific region (n=20), Latin America and the Caribbean (n=7), North America (n=7), Central Africa (n=12), East Africa (n=51), Southern Africa (n=16) and West Africa (n=15). We computed a measure of the comprehensiveness of care based on seven World Health Organization-recommended essential HIV services.
Results
Most sites reported serving urban (61%; region range (rr): 33–100%) and both adult and paediatric populations (77%; rr: 29–96%). Only 45% of HIV clinics that reported treating children had paediatricians on staff. As for the seven essential services, survey respondents reported that CD4+ cell count testing was available to all but one site, while tuberculosis (TB) screening and community outreach services were available in 80 and 72%, respectively. The remaining four essential services – nutritional support (82%), combination antiretroviral therapy adherence support (88%), prevention of mother-to-child transmission (PMTCT) (94%) and other prevention and clinical management services (97%) – were uniformly available. Approximately half (46%) of sites reported offering all seven services. Newer sites and sites in settings with low rankings on the UN Human Development Index (HDI), especially those in the President's Emergency Plan for AIDS Relief focus countries, tended to offer a more comprehensive array of essential services. HIV care programme characteristics and comprehensiveness varied according to the number of years the site had been in operation and the HDI of the site setting, with more recently established clinics in low-HDI settings reporting a more comprehensive array of available services. Survey respondents frequently identified contact tracing of patients, patient outreach, nutritional counselling, onsite viral load testing, universal TB screening and the provision of isoniazid preventive therapy as unavailable services.
Conclusions
This study serves as a baseline for on-going monitoring of the evolution of care delivery over time and lays the groundwork for evaluating HIV treatment outcomes in relation to site capacity for comprehensive care.
doi:10.7448/IAS.17.1.19045
PMCID: PMC4268491  PMID: 25516092
HIV/AIDS; HIV care capacity; clinic characteristics; comprehensive care; resource-limited settings
6.  Strong Agreement of Nationally Recommended Retention Measures from the Institute of Medicine and Department of Health and Human Services 
PLoS ONE  2014;9(11):e111772.
Objective
We sought to quantify agreement between Institute of Medicine (IOM) and Department of Health and Human Services (DHHS) retention indicators, which have not been compared in the same population, and assess clinical retention within the largest HIV cohort collaboration in the U.S.
Design
Observational study from 2008–2010, using clinical cohort data in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
Methods
Retention definitions used HIV primary care visits. The IOM retention indicator was: ≥2 visits, ≥90 days apart, each calendar year. This was extended to a 2-year period; retention required meeting the definition in both years. The DHHS retention indicator was: ≥1 visit each semester over 2 years, each ≥60 days apart. Kappa statistics detected agreement between indicators and C statistics (areas under Receiver-Operating Characteristic curves) from logistic regression analyses summarized discrimination of the IOM indicator by the DHHS indicator.
Results
Among 36,769 patients in 2008–2009 and 34,017 in 2009–2010, there were higher percentages of participants retained in care under the IOM indicator than the DHHS indicator (80% vs. 75% in 2008–2009; 78% vs. 72% in 2009–2010, respectively) (p<0.01), persisting across all demographic and clinical characteristics (p<0.01). There was high agreement between indicators overall (κ = 0.83 in 2008–2009; κ = 0.79 in 2009–2010, p<0.001), and C statistics revealed a very strong ability to predict retention according to the IOM indicator based on DHHS indicator status, even within characteristic strata.
Conclusions
Although the IOM indicator consistently reported higher retention in care compared with the DHHS indicator, there was strong agreement between IOM and DHHS retention indicators in a cohort demographically similar to persons living with HIV/AIDS in the U.S. Persons with poorer retention represent subgroups of interest for retention improvement programs nationally, particularly in light of the White House Executive Order on the HIV Care Continuum.
doi:10.1371/journal.pone.0111772
PMCID: PMC4222946  PMID: 25375099
7.  HIV Diversity as a Biomarker for HIV Incidence Estimation: Including a High-Resolution Melting Diversity Assay in a Multiassay Algorithm 
Journal of Clinical Microbiology  2014;52(1):115-121.
Multiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.
doi:10.1128/JCM.02040-13
PMCID: PMC3911463  PMID: 24153134
8.  Motivational interviewing by HIV care providers is associated with patient intentions to reduce unsafe sexual behavior 
Patient education and counseling  2013;93(1):122-129.
Objective
Motivational Interviewing (MI) can promote behavior change, but HIV care providers rarely have training in MI. Little is known about the use of MI-consistent behavior among untrained providers. This study examines the prevalence of such behaviors and their association with patient intentions to reduce high-risk sexual behavior.
Methods
Audio-recorded visits between HIV-infected patients and their healthcare providers were searched for counseling dialogue regarding sexual behavior. The association of providers’ MI-consistence with patients’ statements about behavior change was assessed.
Results
Of 417 total encounters, 27 met inclusion criteria. The odds of patient commitment to change were higher when providers used more reflections (p=0.017), used more MI consistent utterances (p=0.044), demonstrated more empathy (p=0.049), and spent more time discussing sexual behavior (p=0.023). Patients gave more statements in favor of change (change talk) when providers used more reflections (p<0.001) and more empathy (p<0.001), even after adjusting for length of relevant dialogue.
Conclusion
Untrained HIV providers do not consistently use MI techniques when counseling patients about sexual risk reduction. However, when they do, their patients are more likely to express intentions to reduce sexual risk behavior.
Practice Implications
MI holds promise as one strategy to reduce transmission of HIV and other sexually-transmitted infections.
doi:10.1016/j.pec.2013.04.001
PMCID: PMC3759567  PMID: 23647982
Motivational Interviewing; Physicians; HIV/AIDS; Sexual risk reduction; Counseling
9.  Herpes Zoster among Persons Living with HIV in the Current ART Era 
Background
Previously, herpes zoster (HZ) was found to occur at a higher rate in the HIV population than the general population. There are, however, limited data about the incidence, risk factors, and clinical outcomes of HZ in the current antiretroviral therapy (ART) era.
Methods
We identified HZ episodes in an urban HIV clinic cohort between 2002-2009. Three controls were matched to each case and conditional logistic regression was used to assess for risk factors associated with incident HZ cases. Logistic regression to assess for factors associated with complicated HZ.
Results
183 new HZ cases were identified in 4,353 patients with 19,752 person-years (PY) of follow-up—an incidence rate 9.3/1000 PY. Cases were majority male (62%), and African-American (75%), with a mean age of 39 (IQR 32-44). 50 patients (28%) had complicated HZ with 12% developing post-herpetic neuralgia. In multivariate regression, having started ART within 90 days of the episode (Adjusted OR 4.02, 95% CI:[1.31,12.41]), having a viral load of > 400 copies/mL (1.49, [1.00,2.24]), and having a CD4 <350 cells/mm3 (2.46, [1.42,4.23]) or 350-500 (2.02, [1.14,3.57]) as compared to CD4 > 500 were associated with increased risk of HZ.
Conclusions
The incidence of HZ is lower than previously reported in HIV cohorts, but remains higher than the general population. Over one-fourth of patients developed complicated HZ, which is remarkable given the young age of our population. Risk factors for HZ include markers of poor immune function, suggesting that appropriate ART may reduce the burden of HZ in this population.
doi:10.1097/QAI.0b013e318266cd3c
PMCID: PMC4154488  PMID: 22766968
11.  Incidence and Timing of Cancer in HIV-Infected Individuals Following Initiation of Combination Antiretroviral Therapy 
Kaposi sarcoma and lymphoma rates were highest immediately after antiretroviral therapy (ART) initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART. Calendar year of ART initiation was not associated with subsequent cancer incidence.
Background
Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized.
Methods
We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation.
Results
At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000–2007) and median CD4 count was 202 cells/mm3 (IQR, 61–338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%–13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus–related cancer. Calendar year of ART initiation was not associated with cancer incidence.
Conclusions
KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.
doi:10.1093/cid/cit369
PMCID: PMC3739467  PMID: 23735330
HIV-associated malignancies; AIDS-defining cancer; non-AIDS-defining cancer; combination antiretroviral therapy
12.  THIRTY-DAY HOSPITAL READMISSION RATE AMONG ADULTS LIVING WITH HIV 
AIDS (London, England)  2013;27(13):10.1097/QAD.0b013e3283623d5f.
Objective
Thirty-day hospital readmission rate is receiving increasing attention as a quality of care indicator. The objective of this study was to determine readmission rates and to identify factors associated with readmission among persons living with HIV.
Design
Prospective multicenter observational cohort.
Setting
Nine U.S. HIV clinics affiliated through the HIV Research Network.
Subjects
Patients engaged in HIV care during 2005–2010.
Main outcome measure(s)
Readmission rate was defined as the proportion of hospitalizations followed by a readmission within 30 days. Factors in multivariate analyses included diagnostic categories, patient demographic and clinical characteristics, and having an outpatient follow-up visit.
Results
Among 11,651 total index hospitalizations, the 30-day readmission rate was 19.3%. AIDS defining illnesses (ADI, 9.6% of index hospitalizations) and non-AIDS defining infections (26.4% of index hospitalizations) had readmission rates of 26.2% and 16.6%, respectively. Factors independently associated with readmission included lower CD4 count (AOR 1.80 [1.53, 2.11] for CD4 <50 vs. ≥351 cells/μl), longer length of stay (1.77 [1.53, 2.04] for ≥9 days vs. 1–3 days), and several diagnostic categories including ADI. Having an outpatient follow-up clinic visit was not associated with lower readmission risk (AHR 0.98 [0.88, 1.08]).
Conclusions
The 19.3% readmission rate exceeds the 13.2% rate reported for the general population of 18–64 year-olds. HIV providers may use the 19.3% rate as a basis of comparison. Policymakers may consider the impact of HIV when estimating expected readmissions for a hospital or region. Preventing or recovering from severe immune dysfunction may be the most important factor to reducing readmissions.
doi:10.1097/QAD.0b013e3283623d5f
PMCID: PMC3796165  PMID: 23612008
Readmission; HIV; AIDS defining illness; Outpatient hospital follow-up; Healthcare utilization
13.  Temporal Trends in Presentation and Survival for HIV-Associated Lymphoma in the Antiretroviral Therapy Era 
Background
Lymphoma is the leading cause of cancer-related death among HIV-infected patients in the antiretroviral therapy (ART) era.
Methods
We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems from 1996 until 2010. We examined differences stratified by histology and diagnosis year. Mortality and predictors of death were analyzed using Kaplan–Meier curves and Cox proportional hazards.
Results
Of 23 050 HIV-infected individuals, 476 (2.1%) developed lymphoma (79 [16.6%] Hodgkin lymphoma [HL]; 201 [42.2%] diffuse large B-cell lymphoma [DLBCL]; 56 [11.8%] Burkitt lymphoma [BL]; 54 [11.3%] primary central nervous system lymphoma [PCNSL]; and 86 [18.1%] other non-Hodgkin lymphoma [NHL]). At diagnosis, HL patients had higher CD4 counts and lower HIV RNA than NHL patients. PCNSL patients had the lowest and BL patients had the highest CD4 counts among NHL categories. During the study period, CD4 count at lymphoma diagnosis progressively increased and HIV RNA decreased. Five-year survival was 61.6% for HL, 50.0% for BL, 44.1% for DLBCL, 43.3% for other NHL, and 22.8% for PCNSL. Mortality was associated with age (adjusted hazard ratio [AHR] = 1.28 per decade increase, 95% confidence interval [CI] = 1.06 to 1.54), lymphoma occurrence on ART (AHR = 2.21, 95% CI = 1.53 to 3.20), CD4 count (AHR = 0.81 per 100 cell/µL increase, 95% CI = 0.72 to 0.90), HIV RNA (AHR = 1.13 per log10copies/mL, 95% CI = 1.00 to 1.27), and histology but not earlier diagnosis year.
Conclusions
HIV-associated lymphoma is heterogeneous and changing, with less immunosuppression and greater HIV control at diagnosis. Stable survival and increased mortality for lymphoma occurring on ART call for greater biologic insights to improve outcomes.
doi:10.1093/jnci/djt158
PMCID: PMC3748003  PMID: 23892362
14.  Hepatitis C Virus Testing in Adults Living with HIV: A Need for Improved Screening Efforts 
PLoS ONE  2014;9(7):e102766.
Objectives
Guidelines recommend hepatitis C virus (HCV) screening for all people living with HIV (PLWH). Understanding HCV testing practices may improve compliance with guidelines and can help identify areas for future intervention.
Methods
We evaluated HCV screening and unnecessary repeat HCV testing in 8,590 PLWH initiating care at 12 U.S. HIV clinics between 2006 and 2010, with follow-up through 2011. Multivariable logistic regression examined the association between patient factors and the outcomes: HCV screening (≥1 HCV antibody tests during the study period) and unnecessary repeat HCV testing (≥1 HCV antibody tests in patients with a prior positive test result).
Results
Overall, 82% of patients were screened for HCV, 18% of those screened were HCV antibody-positive, and 40% of HCV antibody-positive patients had unnecessary repeat HCV testing. The likelihood of being screened for HCV increased as the number of outpatient visits rose (adjusted odds ratio 1.02, 95% confidence interval 1.01–1.03). Compared to men who have sex with men (MSM), patients with injection drug use (IDU) were less likely to be screened for HCV (0.63, 0.52–0.78); while individuals with Medicaid were more likely to be screened than those with private insurance (1.30, 1.04–1.62). Patients with heterosexual (1.78, 1.20–2.65) and IDU (1.58, 1.06–2.34) risk compared to MSM, and those with higher numbers of outpatient (1.03, 1.01–1.04) and inpatient (1.09, 1.01–1.19) visits were at greatest risk of unnecessary HCV testing.
Conclusions
Additional efforts to improve compliance with HCV testing guidelines are needed. Leveraging health information technology may increase HCV screening and reduce unnecessary testing.
doi:10.1371/journal.pone.0102766
PMCID: PMC4102540  PMID: 25032989
15.  Improvement in the Health of HIV-Infected Persons in Care: Reducing Disparities 
Over the past 15 years in our clinic, there have been significant improvements in the use of antiretroviral therapy and in the laboratory and clinical responses to therapy. These benefits have similarly affected our patients regardless of sex, race, and human immunodeficiency virus transmission risk group.
Background. Despite advances in human immunodeficiency virus (HIV) treatment, major challenges remain in achieving access, retention, and adherence. Our inner-city HIV clinical practice in Baltimore has a diverse patient population with high rates of poverty, black race, and injection drug use (IDU), providing us the opportunity to compare health process and outcomes.
Methods. Using data collected in a clinical HIV cohort in Baltimore, we compared receipt of combination antiretroviral therapy (ART), HIV type 1 (HIV-1) RNA, CD4, incidence of opportunistic illness, and mortality from 1995 to 2010. Comparisons were made of these outcomes by HIV risk group, sex, and race (black, white).
Results. From 1995 to 2010, we followed 6366 patients comprising 27 941 person-years (PY) of follow-up. By 2010, 87% of patients were receiving ART; median HIV-1 RNA was <200 copies/mL, median CD4 was 475 cells/mm3, opportunistic illness rates were 2.4 per 100 PY, and mortality rates were 2.1 per 100 PY, with no differences by demographic or HIV risk group. The only differences were that the IDU risk group had a median CD4 that was 79 cells/mm3 lower and HIV-1 RNA 0.16 log10 copies/mL higher compared with other risk groups (P < .01). In 2009 a 28-year-old HIV-infected person was estimated to have 45.4 years of life remaining, which did not differ by demographic or behavioral risk group.
Discussion. Our results emphasize that advances in HIV treatment have had a positive impact on all affected demographic and behavioral risk groups in an HIV clinical setting, with an expected longevity for HIV-infected patients that is now 73 years.
doi:10.1093/cid/cis654
PMCID: PMC3466093  PMID: 23019271
16.  Survival during Renal Replacement Therapy among African Americans Infected with HIV Type 1 in Urban Baltimore, Maryland 
Background
African Americans with human immunodeficiency virus type 1 (HIV-1) infection and kidney disease are at increased risk of end-stage renal disease requiring renal replacement therapy (RRT), particularly in urban areas with high rates of poverty and injection drug use. It is unknown how the widespread use of highly active antiretroviral therapy (HAART) has affected survival during RRT in this vulnerable population.
Methods
African American patients infected with HIV-1 who required RRT were identified from 2 cohorts that included 4509 Africans Americans infected with HIV-1 who were recruited during the period 1988–2004 in Baltimore, Maryland. Survival after initiation of RRT was compared for those who initiated treatment in the pre-HAART and the HAART eras using Kaplan-Meier curves. Cox proportional hazards regression analysis was used to adjust for potential confounders.
Results
RRT was initiated in 162 patients (3.6%) during 10.6 years of follow-up (119 during the HAART era). Compared with patients who started RRT in the pre-HAART era, those in the HAART era were older (P< .001) and more likely to have CD4 cell counts of ≥200 cells/mm3 (P = .01). A total of 126 patients (78%) died during follow-up; among those who initiated RRT during the HAART era, 87 deaths occurred (73%). Median survival time in the pre-HAART era was 22.4 months (95% confidence interval [CI], 9.3–30.7); during the HAART era, it was 19.9 months (95% CI, 14.7–26.5; P = .94). In the multiple Cox regression model, factors independently associated with increased mortality included age (hazard ratio [HR], 1.30; 95% CI, 1.06–1.60; P = .01), lower serum albumin level (HR, 0.72; 95% CI, 0.57–0.91; P< .007), lower CD4 cell count (HR, 0.90; 95% CI, 0.82–0.99; P< .03), and the lack of HAART (HR, 0.52; 95% CI, 0.33–0.82; P = .005).
Conclusions
Older age, lower serum albumin level, lower CD4 cell count, and the lack of HAART are independent predictors of poor survival among African Americans infected with HIV-1 undergoing RRT in a resource-limited urban area. RRT survival was similar in the pre-HAART and HAART eras, likely reflecting inadequate HIV treatment in this population.
doi:10.1086/523728
PMCID: PMC4096866  PMID: 18190325
17.  The impact of depressive symptoms on patient–provider communication in HIV care 
AIDS care  2013;25(9):1185-1192.
Persons with HIV who develop depression have worse medical adherence and outcomes. Poor patient–provider communication may play a role in these outcomes. This cross-sectional study evaluated the influence of patient depression on the quality of patient–provider communication. Patient–provider visits (n = 406) at four HIV care sites were audio-recorded and coded with the Roter Interaction Analysis System (RIAS). Negative binomial and linear regressions using generalized estimating equations tested the association of depressive symptoms, as measured by the Center for Epidemiology Studies Depression scale (CES-D), with RIAS measures and postvisit patient-rated quality of care and provider-reported regard for his or her patient. The patients, averaged 45 years of age (range = 20–77), were predominately male (n = 286, 68.5%), of black race (n = 250, 60%), and on antiretroviral medications (n = 334, 80%). Women had greater mean CES-D depression scores (12.0) than men (10.6; p = 0.03). There were no age, race, or education differences in depression scores. Visits with patients reporting severe depressive symptoms compared to those reporting none/mild depressive symptoms were longer and speech speed was slower. Patients with severe depressive symptoms did more emotional rapport building but less social rapport building, and their providers did more data gathering/counseling (ps < 0.05). In postvisit questionnaires, providers reported lower levels of positive regard for, and rated more negatively patients reporting more depressive symptoms (p < 0.01). In turn, patients reporting more depressive symptoms felt less respected and were less likely to report that their provider knows them as a person than none/mild depressive symptoms patients (ps < 0.05). Greater psychosocial needs of patients presenting with depressive symptoms and limited time/resources to address these needs may partially contribute to providers’ negative attitudes regarding their patients with depressive symptoms. These negative attitudes may ultimately serve to adversely impact patient–provider communication and quality of HIV care.
doi:10.1080/09540121.2012.752788
PMCID: PMC4090599  PMID: 23320529
depression; communication; quality of health care; patient satisfaction; HIV
18.  High Levels of Antiretroviral Use and Viral Suppression among Persons in HIV Care in the United States, 2010 
Background
Contemporary data on patterns of antiretroviral therapy (ART) use in the U.S. 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/mm3), 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 (VL) in 2010, 94% had ever initiated ART, 89% were on ART, and 70% had an undetectable VL at the end of 2010. Fifty percent of ART-naïve patients had nadir CD4 counts >500 cells/mm3, but this group composed just 3% of the total population. Among patients who were ART-naïve 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/mm3 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 prior studies and increased from 2009 to 2010.
doi:10.1097/QAI.0b013e3182945bc7
PMCID: PMC3691075  PMID: 23572013
Antiretroviral Therapy, Highly Active; HIV Infections/drug therapy; HIV Infections/prevention & control; Patient Acceptance of Health Care/statistics & numerical data; United States
19.  Counseling to Reduce High-Risk Sexual Behavior in HIV Care: A Multi-Center, Direct Observation Study 
AIDS Patient Care and STDs  2013;27(7):416-424.
Abstract
A key opportunity to reduce HIV transmission lies with healthcare providers counseling HIV-infected patients about safer sex. We audio-recorded and transcribed clinical encounters between 45 healthcare providers and 417 of their HIV-infected patients at four outpatient sites in the United States. We used logistic regressions to evaluate associations between patient and provider characteristics, and the occurrence of discussion (any talk about sex) and counseling (advice about safer sex). Of the 417 encounters, discussion of sex occurred in 187 (45% of encounters, 95% CI: 40–50%). Counseling occurred for 49% (95% CI: 35–63%) of patients reporting unsafe sex. Discussion of sex was more likely with younger or less-educated patients and with less cultural difference between patient and provider, while counseling was associated with greater provider mindfulness and lower provider empathy. These findings suggest targets to improve communication regarding sexual risk reduction in HIV care.
doi:10.1089/apc.2012.0426
PMCID: PMC3704109  PMID: 23802144
20.  Higher Quality Communication and Relationships are Associated with Improved Patient Engagement in HIV Care 
Patient retention in HIV care may be influenced by patient-provider interactions. In an urban, academic HIV clinic, 1363 patients rated the quality of communication and relationships with their providers on five domains. We used linear regressions to investigate associations between these 5 domains and appointment adherence. In multivariate analysis, patients kept more appointments if providers treated them with dignity and respect, listened carefully to them, explained in ways they could understand, and knew them as persons. Being involved in decisions was not significantly associated with appointment adherence. Enhancing providers’ skills in effective communication and relationship-building may improve patient retention in HIV care.
doi:10.1097/QAI.0b013e318295b86a
PMCID: PMC3752691  PMID: 23591637
HIV/AIDS; retention; engagement; communication; patient-provider relationship
21.  A Comparison of Two Measures of HIV Diversity in Multi-Assay Algorithms for HIV Incidence Estimation 
PLoS ONE  2014;9(6):e101043.
Background
Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.
Methods
Both MAAs included two serologic assays (LAg-Avidity assay and BioRad-Avidity assay), HIV viral load, and an HIV diversity assay. HIV diversity was quantified using either a high resolution melting (HRM) diversity assay that does not require HIV sequencing (HRM score for a 239 base pair env region) or sequence ambiguity (the percentage of ambiguous bases in a 1,302 base pair pol region). Samples were classified as MAA positive (likely from individuals with recent HIV infection) if they met the criteria for all of the assays in the MAA. The following performance characteristics were assessed: (1) the proportion of samples classified as MAA positive as a function of duration of infection, (2) the mean window period, (3) the shadow (the time period before sample collection that is being assessed by the MAA), and (4) the accuracy of cross-sectional incidence estimates for three cohort studies.
Results
The proportion of samples classified as MAA positive as a function of duration of infection was nearly identical for the two MAAs. The mean window period was 141 days for the HRM-based MAA and 131 days for the sequence ambiguity-based MAA. The shadows for both MAAs were <1 year. Both MAAs provided cross-sectional HIV incidence estimates that were very similar to longitudinal incidence estimates based on HIV seroconversion.
Conclusions
MAAs that include the LAg-Avidity assay, the BioRad-Avidity assay, HIV viral load, and HIV diversity can provide accurate HIV incidence estimates. Sequence ambiguity measures obtained using a commercially-available HIV genotyping system can be used as an alternative to HRM scores in MAAs for cross-sectional HIV incidence estimation.
doi:10.1371/journal.pone.0101043
PMCID: PMC4072769  PMID: 24968135
22.  Hematologic, Hepatic, Renal and Lipid Laboratory Monitoring Following Initiation of Combination Antiretroviral Therapy in the United States, 2000–2010 
We assessed laboratory monitoring following combination antiretroviral therapy (cART) initiation among 3,678 patients in a large US multi-site clinical cohort, censoring participants at last clinic visit, cART change, or three years. Median days (interquartile range) to first hematologic, hepatic, renal and lipid tests were 30 (18–53), 31 (19–56), 33 (20–59) and 350 (96–1106), respectively. At one year, approximately 80% received more than two hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received one or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities.
doi:10.1097/QAI.0b013e31828d69f1
PMCID: PMC3654034  PMID: 23446495
Laboratory Monitoring; Antiretroviral Therapy; Antiretroviral Toxicity
23.  Changing predictors of mortality over time from cART start: implications for care 
Objective
To determine predictors of mortality and changes in those predictors over time on combination antiretroviral therapy (cART) in South Africa.
Design
A cohort study.
Methods
Using routine clinic data with up to 4 years follow-up after ART initiation and with death ascertainment from a national vital statistics register, we used proportional hazards modeling to assess baseline and time-updated predictors of mortality, and changes in strength of those predictors over time on cART. Furthermore, we compared CD4 count among individuals who died by duration on cART.
Results
15,060 subjects (64% men, median CD4 count 127 cells/mm3) started antiretroviral therapy between January 2003 and January 2008. Over a median follow-up of 1.8 years, 2,658 subjects died. The baseline characteristics of WHO stage, haemoglobin, CD4 count, HIV RNA level, and symptoms were all associated with mortality during the first 12 months of cART but lost association thereafter. However time updated factors of CD4 count, body mass index, symptoms, anemia, and HIV RNA suppression remained strong predictors of death. Most recent CD4 count prior to death rose from 71 during the first 3 months of cART to 175 cells/mm3 after >3 years of cART.
Conclusion
Over 4 years of cART, risk of death declined and associations with mortality changed. An increase in CD4 count at death and changing associations with mortality may suggest a shift in causes of death, possibly from opportunistic infections to other infections and chronic illnesses.
doi:10.1097/QAI.0b013e31823219d1
PMCID: PMC4009722  PMID: 21876447
mortality; HIV; resource limited setting; Africa; antiretroviral therapy; proportional hazards
24.  Primary Care Provider Cultural Competence and Racial Disparities in HIV Care and Outcomes 
ABSTRACT
BACKGROUND
Health professional organizations have advocated for increasing the “cultural competence” (CC) of healthcare providers, to reduce racial and ethnic disparities in patient care. It is unclear whether provider CC is associated with more equitable care.
OBJECTIVE
To evaluate whether provider CC is associated with quality of care and outcomes for patients with HIV/AIDS.
DESIGN AND PARTICIPANTS
Survey of 45 providers and 437 patients at four urban HIV clinics in the U.S.
MAIN MEASURES
Providers’ self-rated CC was measured using a novel, 20-item instrument. Outcome measures included patients’ receipt of antiretroviral (ARV) therapy, self-efficacy in managing medication regimens, complete 3-day ARV adherence, and viral suppression.
KEY RESULTS
Providers’ mean age was 44 years; 56 % were women, and 64 % were white. Patients’ mean age was 45; 67 % were men, and 77 % were nonwhite. Minority patients whose providers scored in the middle or highest third on self-rated CC were more likely than those with providers in the lowest third to be on ARVs, have high self-efficacy, and report complete ARV adherence. Racial disparities were observed in receipt of ARVs (adjusted OR, 95 % CI for white vs. nonwhite: 6.21, 1.50–25.7), self-efficacy (3.77, 1.24–11.4), and viral suppression (13.0, 3.43–49.0) among patients of low CC providers, but not among patients of moderate and high CC providers (receipt of ARVs: 0.71, 0.32–1.61; self-efficacy: 1.14, 0.59–2.22; viral suppression: 1.20, 0.60–2.42).
CONCLUSIONS
Provider CC was associated with the quality and equity of HIV care. These findings suggest that enhancing provider CC may reduce racial disparities in healthcare quality and outcomes.
doi:10.1007/s11606-012-2298-8
PMCID: PMC3631054  PMID: 23307396
culture; ethnic groups; HIV
25.  Race, Relationships and Trust in Providers among Black Patients with HIV/AIDS 
Social work research  2013;37(3):219-226.
A trustful patient-provider relationship is a strong predictor of positive outcomes, including treatment adherence and viral suppression, among patients with HIV/AIDS. Understanding factors that inform this relationship is especially relevant for Black patients, who bear a disproportionate burden of HIV morbidity and mortality, and may face challenges associated with seeing providers of a racial/ethnic background that is different from their own. Using data collected through the Enhancing Communication and HIV Outcomes (ECHO) study, we build upon extant research by examining patient and provider characteristics that may influence Black patients’ trust in their provider. ECHO data were collected from four ambulatory care sites in Baltimore, Detroit, New York and Portland, Oregon (N=435). Regression analysis results indicate that trust in health care institutions and cultural similarity between patient and provider are strongly associated with patients’ trust in their provider. Lower perceived social status, being currently employed, and having an older provider were also related to greater patient-provide trust. These findings can inform interventions to improve trust and reduce disparities in HIV care and outcomes that stem from mistrust among Black patients.
doi:10.1093/swr/svt017
PMCID: PMC3994892  PMID: 24764690
Blacks; trust; physician-patient relations; culture; HIV/AIDS

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