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1.  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.
PMCID: PMC4357817  PMID: 25409471
end-stage renal disease (ESRD); chronic kidney disease (CKD); HIV infection/AIDS; HIV/AIDS; glomerular filtration rate (GFR)
2.  Enhanced Personal Contact With HIV Patients Improves Retention in Primary Care: A Randomized Trial in 6 US HIV Clinics 
Gardner, Lytt I. | Giordano, Thomas P. | Marks, Gary | Wilson, Tracey E. | Craw, Jason A. | Drainoni, Mari-Lynn | Keruly, Jeanne C. | Rodriguez, Allan E. | Malitz, Faye | Moore, Richard D. | Bradley-Springer, Lucy A. | Holman, Susan | Rose, Charles E. | Girde, Sonali | Sullivan, Meg | Metsch, Lisa R. | Saag, Michael | Mugavero, Michael J. | Drainoni, Mari-Lynn | Ferreira, Cintia | Koppelman, Lisa | McDoom, Maya | Naisteter, Michal | Osella, Karina | Ruiz, Glory | Skolnik, Paul | Sullivan, Meg | Gibbs-Cohen, Sophia | Desrivieres, Elana | Frederick, Mayange | Gravesande, Kevin | Holman, Susan | Johnson, Harry | Taylor, Tonya | Wilson, Tracey | Cheever, Laura | Malitz, Faye | Mills, Robert | Craw, Jason | Gardner, Lytt | Girde, Sonali | Marks, Gary | Batey, Scott | Gaskin, Stephanie | Mugavero, Michael | Murphree, Jill | Raper, Jim | Saag, Michael | Thogaripally, Suneetha | Willig, James | Zinski, Anne | Arya, Monisha | Bartholomew, David | Biggs, Tawanna | Budhwani, Hina | Davila, Jessica | Giordano, Tom | Miertschin, Nancy | Payne, Shapelle | Slaughter, William | Jenckes, Mollie | Keruly, Jeanne | McCray, Angie | McGann, Mary | Moore, Richard | Otterbein, Melissa | Zhou, Liming | Garzon, Carolyn | Jean-Simon, Jesline | Mercogliano, Kathy | Metsch, Lisa | Rodriguez, Allan | Saint-Jean, Gilbert | Shika, Marvin | Bradley-Springer, Lucy | Corwin, Marla
The intervention tested in the Retention in Care Study demonstrated improvement in retention in human immunodeficiency virus care. Enhanced personal contact with or without additional behavioral skills training significantly improved visit constancy and visit adherence over 12 months.
Background. The aim of the study was to determine whether enhanced personal contact with human immunodeficiency virus (HIV)–infected patients across time improves retention in care compared with existing standard of care (SOC) practices, and whether brief skills training improves retention beyond enhanced contact.
Methods. The study, conducted at 6 HIV clinics in the United States, included 1838 patients with a recent history of inconsistent clinic attendance, and new patients. Each clinic randomized participants to 1 of 3 arms and continued to provide SOC practices to all enrollees: enhanced contact with interventionist (EC) (brief face-to-face meeting upon returning for care visit, interim visit call, appointment reminder calls, missed visit call); EC + skills (organization, problem solving, and communication skills); or SOC only. The intervention was delivered by project staff for 12 months following randomization. The outcomes during that 12-month period were (1) percentage of participants attending at least 1 primary care visit in 3 consecutive 4-month intervals (visit constancy), and (2) proportion of kept/scheduled primary care visits (visit adherence).
Results. Log-binomial risk ratios comparing intervention arms against the SOC arm demonstrated better outcomes in both the EC and EC + skills arms (visit constancy: risk ratio [RR], 1.22 [95% confidence interval {CI}, 1.09–1.36] and 1.22 [95% CI, 1.09–1.36], respectively; visit adherence: RR, 1.08 [95% CI, 1.05–1.11] and 1.06 [95% CI, 1.02–1.09], respectively; all Ps < .01). Intervention effects were observed in numerous patient subgroups, although they were lower in patients reporting unmet needs or illicit drug use.
Conclusions. Enhanced contact with patients improved retention in HIV primary care compared with existing SOC practices. A brief patient skill-building component did not improve retention further. Additional intervention elements may be needed for patients reporting illicit drug use or who have unmet needs.
Clinical Trials Registration. CDCHRSA9272007.
PMCID: PMC4366591  PMID: 24837481
behavioral intervention trial; HIV infection; HIV specialty clinics; randomized controlled trial; retention in care
3.  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.
PMCID: PMC3967825  PMID: 24463281
HIV; quality of care; retention in care; antiretroviral therapy; HIV RNA suppression
4.  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.
PMCID: PMC3778973  PMID: 23904290
HIV; hepatitis C virus; chronic kidney disease; hepatitis C RNA; cohort study; glomerular filtration rate; injection drug use
5.  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.
PMCID: PMC3657490  PMID: 23315317
antiretroviral therapy; healthcare disparities; HIV; time factors; viral load
6.  A Randomized Controlled Trial Protocol to Evaluate the Effectiveness of an Integrated Care Management Approach to Improve Adherence Among HIV-Infected Patients in Routine Clinical Care: Rationale and Design 
JMIR Research Protocols  2016;5(4):e156.
Adherence to antiretroviral medications is a key determinant of clinical outcomes. Many adherence intervention trials investigated the effects of time-intensive or costly interventions that are not feasible in most clinical care settings.
We set out to evaluate a collaborative care approach as a feasible intervention applicable to patients in clinical care including those with mental illness and/or substance use issues.
We developed a randomized controlled trial (RCT) investigating an integrated, clinic-based care management approach to improve clinical outcomes that could be integrated into the clinical care setting. This is based on the routine integration and systematic follow-up of a clinical assessment of patient-reported outcomes targeting adherence, depression, and substance use, and adapts previously developed and tested care management approaches. The primary health coach or care management role is provided by clinic case managers allowing the intervention to be generalized to other human immunodeficiency virus (HIV) clinics that have case managers. We used a stepped-care approach to target interventions to those at greatest need who are most likely to benefit rather than to everyone to maintain feasibility in a busy clinical care setting.
The National Institutes of Health funded this study and had no role in study design, data collection, or decisions regarding whether or not to submit manuscripts for publication. This trial is currently underway, enrollment was completed in 2015, and follow-up time still accruing. First results are expected to be ready for publication in early 2017.
This paper describes the protocol for an ongoing clinical trial including the design and the rationale for key methodological decisions. There is a need to identify best practices for implementing evidence-based collaborative care models that are effective and feasible in clinical care. Adherence efficacy trials have not led to sufficient improvements, and there remains little guidance regarding how adherence interventions should be implemented into clinical care. By focusing on improving adherence within care settings using existing staff, routine assessment of key domains, such as depression, adherence, and substance use, and feasible interventions, we propose to evaluate this innovative way to improve clinical outcomes.
Trial Registration NCT01505660; (Archived by WebCite at http://www.webcitation/ 6ktOq6Xj7)
PMCID: PMC5071617  PMID: 27707688
adherence; randomized controlled trial; depression; substance use; alcohol use; intervention; HIV; care management
7.  Characterizing Failure to Establish Hepatitis C Care of Baby Boomers Diagnosed in the Emergency Department 
Open Forum Infectious Diseases  2016;3(4):ofw211.
Emergency departments (EDs) are high-yield sites for hepatitis C virus (HCV) screening, but data regarding linkage to care (LTC) determinants are limited.
Between September 2013 and June 2014, 4371 baby boomers unaware of their HCV status presented to the University of Alabama at Birmingham ED and underwent opt-out screening. A linkage coordinator facilitated referrals for positive cases. Demographic data, International Classification of Diseases, Ninth Revision codes, and clinic visits were collected, and patients were (retrospectively) followed up until February 2015. Linkage to care was defined as an HCV clinic visit within the hospital system.
Overall, 332 baby boomers had reactive HCV antibody and detectable plasma ribonucleic acid. The mean age was 57.3 years (standard deviation = 4.8); 70% were male and 61% were African Americans. Substance abuse (37%) and psychiatric diagnoses (30%) were prevalent; 9% were identified with cirrhosis. During a median follow-up of 433 days (interquartile range, 354–500), 117 (35%) linked to care and 48% needed inpatient care. In multivariable analysis, the odds of LTC failure were significantly higher for white males (adjusted odds ratio [aOR], 2.57; 95% confidence interval [CI], 1.03–6.38) and uninsured individuals (aOR, 5.16; 95% CI, 1.43–18.63) and lower for patients with cirrhosis (aOR, 0.36; 95% CI, 0.14–0.92) and access to primary care (aOR, 0.20; 95% CI, 0.10–0.41).
In this cohort of baby boomers with newly diagnosed HCV in the ED, only 1 in 3 were linked to HCV care. Although awareness of HCV diagnosis remains important, intensive strategies to improve LTC and access to curative therapy for diagnosed individuals are needed.
PMCID: PMC5198583  PMID: 28066793
emergency department; hepatitis C screening; linkage to care.
8.  Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults 
JAMA  2016;316(2):191-210.
New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults.
To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis.
A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence.
Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure.
Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.
PMCID: PMC5012643  PMID: 27404187
9.  Obesity Is Associated with Race/Sex Disparities in Diabetes and Hypertension Prevalence, But Not Cardiovascular Disease, Among HIV-Infected Adults 
Race/sex differences are observed in cardiometabolic disease (CMD) risk and prevalence in the context of treated, chronic HIV infection, and these differences could be exacerbated by disparities in obesity prevalence. We sought to determine the effect of obesity on these disparities among people living with HIV. Prevalence of CMD (dyslipidemia, cardiovascular disorders, hypertension, diabetes, chronic kidney disease) was determined for patients seen at the University of Alabama at Birmingham HIV clinic between 7/2010 and 6/2011. Staged logistic regression was used to examine the impact of race/sex on comorbidities adjusting for key confounders including/excluding obesity (body mass index ≥30 kg/m2). Of 1,800 participants, 77% were male, 54% were black, and 25% were obese. Obesity prevalence differed by race/sex: black women 49%, black men 24%, white women 24%, white men 15% (p<0.01). Compared to white men, other groups had reduced odds for dyslipidemia and cardiovascular disorders (p<0.01). Black men had increased odds for hypertension and chronic kidney disease, while black women had a nearly 2-fold increased odds for diabetes and hypertension (all at p<0.01). The associations of black women with diabetes and hypertension were attenuated when obesity was included in the models. Other group differences remained significant. Disparities in obesity prevalence do not explain race/sex differences in all CMD among people with HIV. Obesity accounted for associations with diabetes/hypertension for black women, who may benefit from weight reduction to decrease disease risk. Further investigations into the etiology and treatment of CMD in people living with HIV should consider unique race/sex treatment issues.
PMCID: PMC4553382  PMID: 26114374
10.  Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy 
PLoS ONE  2016;11(8):e0160460.
To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years.
We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA.
During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years.
Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes.
PMCID: PMC4985160  PMID: 27525413
11.  Dynamic Visual Display of Treatment Response in HIV-Infected Adults 
A dynamic visual display highlights the dramatic changes in human immunodeficiency virus type 1 (HIV-1) plasma viral load and CD4 cell count after antiretroviral therapy initiation among adults with HIV, providing insight into the heterogeneous treatment outcomes observed among these patients.
Background. Using a dynamic visual display, we examine the changes in human immunodeficiency virus type 1 (HIV-1) plasma viral load and CD4 cell count for 5 years after antiretroviral therapy initiation in a large cohort of patients with HIV.
Methods. Patients at a Centers for AIDS Research Network of Integrated Clinical Systems site who initiated combination antiretroviral therapy between 1 January 2000 and 31 December 2012 were followed for 5 years for HIV-1 plasma viral load, CD4 cell count, and mortality. The joint distribution of CD4 cell count and viral load over time was depicted in an animated display using a bivariate kernel smoother.
Results. Within days of therapy initiation, many patients had a suppressed viral load and their median CD4 cell count had increased. However, the median CD4 cell count remained below normal levels throughout follow-up period and the proportion of patients with high viral load occasionally increased, even years after therapy initiation.
Conclusions. The dramatic changes in viral load and CD4 cell count after therapy initiation highlight the overwhelming effectiveness of antiretroviral therapy in the modern era. However, this work also emphasizes the need for pharmaceutical or behavioral interventions to prevent virologic failure and to stimulate complete recovery of normal CD4 cell count.
PMCID: PMC4481601  PMID: 25838289
HIV/AIDS; antiretroviral therapy
12.  An Algorithm Approach to Determining Smoking Cessation Treatment for Persons Living with HIV/AIDS: Results of a Pilot Trial 
Smoking now represents one of the biggest modifiable risk factors for disease and mortality in PLHIV. To produce significant changes in smoking rates among this population, treatments will need to be both acceptable to the larger segment of PLHIV smokers as well as feasible to implement in busy HIV clinics. The purpose of this study was to evaluate the feasibility and effects of a novel proactive algorithm-based intervention in an HIV/AIDS clinic.
PLHIV smokers (N =100) were proactively identified via their electronic medical records and were subsequently randomized at baseline to receive a 12-week pharmacotherapy-based algorithm treatment or treatment as usual. Participants were tracked in-person for 12-weeks. Participants provided information on smoking behaviors and associated constructs of cessation at each follow-up session.
The findings revealed that many smokers reported utilizing prescribed medications when provided with a supply of cessation medication as determined by an algorithm. Compared to smokers receiving treatment as usual, PLHIV smokers prescribed these medications reported more quit attempts and greater reduction in smoking. Proxy measures of cessation readiness (e.g., motivation, self-efficacy) also favored participants receiving algorithm treatment.
This algorithm-derived treatment produced positive changes across a number of important clinical markers associated with smoking cessation. Given these promising findings coupled with the brief nature of this treatment, the overall pattern of results suggests strong potential for dissemination into clinical settings as well as significant promise for further advancing clinical health outcomes in this population.
PMCID: PMC4505746  PMID: 26181705
HIV; AIDS; Smoking Cessation; Algorithm; Proactive
13.  Unanticipated Effects of New Drug Availability on Antiretroviral Durability: Implications for Comparative Effectiveness Research 
Open Forum Infectious Diseases  2016;3(2):ofw109.
Background. Durability of antiretroviral (ARV) therapy is associated with improved human immunodeficiency virus (HIV) outcomes. Data on ARV regimen durability in recent years and clinical settings are lacking.
Methods. This retrospective follow-up study included treatment-naive HIV-infected patients initiating ARV therapy between January 2007 and December 2012 in a university-affiliated HIV clinic in the Southeastern United States. Outcome of interest was durability (time to discontinuation) of the initial regimen. Durability was evaluated using Kaplan-Meier survival analyses. Cox proportional hazard analyses was used to evaluate the association among durability and sociodemographic, clinical, and regimen-level factors.
Results. Overall, 546 patients were analyzed. Median durability of all regimens was 39.5 months (95% confidence interval, 34.1–44.4). Commonly prescribed regimens were emtricitabine and tenofovir with efavirenz (51%; median duration = 40.1 months) and with raltegravir (14%; 47.8 months). Overall, 67% of patients had an undetectable viral load at the time of regimen cessation. Discontinuation was less likely with an integrase strand transfer inhibitor (adjusted hazards ratio [aHR] = 0.35, P = .001) or protease inhibitor-based regimen (aHR = 0.45, P = .006) and more likely with a higher pill burden (aHR = 2.25, P = .003) and a later treatment era (aHR = 1.64, P < .001).
Conclusions. Initial ARV regimen longevity declined in recent years contemporaneous with the availability of several new ARV drugs and combinations. Reduced durability mostly results from a preference for newly approved regimens rather than indicating failing therapy, as indicated by viral suppression observed in a majority of patients (67%) prior to regimen cessation. Durability is influenced by extrinsic factors including new drug availability and provider preference. Medication durability must be interpreted carefully in the context of a dynamic treatment landscape.
PMCID: PMC4943538  PMID: 27419181
antiretroviral; durability; persistence; prescribing patterns
14.  Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1 
The New England journal of medicine  2015;373(8):705-713.
Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need.
We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 viro-logic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events.
Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 number, NCT02073656.)
PMCID: PMC4892372  PMID: 26196665
15.  Uncompensated Medical Provider Costs Associated with Prior Authorization for Prescription Medications in an HIV Clinic 
Although prior authorization (PA) for prescription medications is widely employed for cost-containment for third-party insurers, it is a frustrating aspect of outpatient clinical care that imposes uncompensated costs to medical providers. To characterize these costs, we monitored the PA-associated administrative and operational process at the University of Alabama at Birmingham 1917 HIV Clinic over a 2-year period. A total of 288 PAs were processed with a mean (± standard deviation [SD]) of days 3.1 ± 5.8 delay in the patient’s access to medication. A mean (± SD) of 26.8 ± 18.4 min was spent by the nurse practitioner and 6.5 ± 2.9 min was spent by a clerk per PA. Nearly three-quarters (73%) of PAs were approved, 18% were denied, and 10% were voided. The mean (± SD) pages of paperwork was 5.8 ± 6.5. The overall cost was $41.60 per PA. Although evidence supports that PA reduces third-party expenditures, it significantly delays medication accessibility for patients and imposes high costs that negatively impact operating margins for health care providers.
PMCID: PMC4892366  PMID: 20695800
16.  Implementation of Computer-delivered Brief Alcohol Intervention in HIV Clinical Settings: Who Agrees to Participate? 
Addressing alcohol use in primary HIV settings can improve medical outcomes and overall quality of life of persons living with HIV (PLWH). In order to assess the feasibility of computer-delivered brief alcohol intervention (CBI) and to inform future efforts to improve access to CBI, we examined patient-level socio-demographic, clinical and behavioral characteristics associated with agreement to participate in CBI among non-treatment seeking PLWH with alcohol misuse.
Participants were recruited from two Centres for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) HIV clinics. PLWH completed a clinical assessment of patient-reported measures and outcomes using tablet-based assessments, including socio-demographic and behavioural characteristics. HIV biological indicators, i.e., CD4 count and viral load, were also available from the electronic medical record. Participants were approached for CBI participation based on scores on the Alcohol Use Disorders Identification Test (AUDIT); no incentives were offered for CBI participation. We performed chi-square tests, analysis of variance and multivariate logistic regression to compare socio-demographic, behavioural and clinical factors among participants who agreed to participate compared with those who refused/postponed participation.
We observed that 42% of non-treatment seeking, non-incentivized PLWH with alcohol misuse provided written agreement to participate in on-site CBI delivered in their HIV primary care clinic. A larger proportion of PLWH who agreed to enrol in CBI had detectable viral loads, heavier weekly alcohol use, and higher DSM-5 alcohol use disorder symptom counts and mental health symptoms. Neither socio-demographic background nor drug use status was associated with CBI enrolment.
CBI implementation reached those patients most in need of care. The findings of this study may assist HIV-care providers to better identify appropriate patients and initiate discussions to facilitate the participation of PLWH in alcohol intervention services.
PMCID: PMC4890715  PMID: 27274904
Alcohol misuse; Brief intervention; HIV; Mental health; Implementation
17.  Quantitative Evaluation of an Instrument to Identify Chronic Pain in HIV-Infected Individuals 
A method to rapidly identify the presence of chronic pain would enhance the care of HIV-infected individuals, but such an instrument has not been assessed in this population to date. We assessed the construct validity of the two-question Brief Chronic Pain Questionnaire (BCPQ) in HIV-infected patients by assessing the association between BCPQ responses and known correlates of chronic pain. Participants in the University of Alabama Center for AIDS Research Network of Integrated Clinical Systems cohort completed the BCPQ, along with the EuroQOL to assess physical function, the PHQ-9 to assess depression, and the PHQ-anxiety module to assess anxiety. Among 100 participants, 25% were female, the mean age was 45 (SD 12), 63% were African American, 27% were publicly insured, the median CD4+ T cell count was 572 cells/mm3 (IQR 307–788), and 82% had an undetectable viral load. Participants with chronic pain were more likely to have impaired mobility (43% vs. 12%, p=0.001), difficulty with usual activities (47% vs. 12%, p<0.001), lower overall health state (70 vs. 84, p=0.002), pain today (80% vs. 27%, p<0.001), depression (30% vs. 15%, p=0.10), and anxiety (43% vs. 10%, p<0.001) than those without chronic pain. This study provides preliminary evidence for the BCPQ as a brief questionnaire to identify the presence of chronic pain in HIV care settings.
PMCID: PMC4458733  PMID: 25693683
18.  When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study 
Supplemental Digital Content is Available in the Text.
To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART).
Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems.
Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9–12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes.
In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9–12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies.
Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.
PMCID: PMC4866894  PMID: 26895294
HIV; CD4 cell count; HIV RNA; monitoring; observational studies; mortality
19.  Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment 
AIDS (London, England)  2016;30(8):1229-1238.
The aim of this study was to evaluate the efficacy of maraviroc along with darunavir/ritonavir, all once daily, for the treatment of antiretroviral-naive HIV-1 infected individuals.
MODERN was a multicentre, double-blind, noninferiority, phase III study in HIV-1 infected, antiretroviral-naive adults with plasma HIV-1 RNA at least 1000 copies/ml and no evidence of reduced susceptibility to study drugs.
At screening, participants were randomized 1 : 1 to undergo either genotypic or phenotypic tropism testing. Participants with CCR5-tropic HIV-1 were randomized 1 : 1 to receive maraviroc 150 mg once daily or tenofovir/emtricitabine once daily each with darunavir/ritonavir once daily for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies/ml (Food and Drug Administration snapshot algorithm) at Week 48. A substudy evaluated bone mineral density, body fat distribution and serum bone turnover markers.
Seven hundred and ninety-seven participants were dosed (maraviroc, n = 396; tenofovir/emtricitabine, n = 401). The Data Monitoring Committee recommended early study termination due to inferior efficacy in the maraviroc group. At Week 48, the proportion of participants with HIV-1 RNA less than 50 copies/ml was 77.3% for maraviroc and 86.8% for tenofovir/emtricitabine [difference of −9.54% (95% confidence interval: −14.83 to −4.24)]. More maraviroc participants discontinued for lack of efficacy, which was not associated with non-R5 tropism or resistance. Discontinuations for adverse events, Category C events, Grade 3/4 adverse events and laboratory abnormalities were similar between groups.
A once-daily nucleos(t)ide-sparing two-drug regimen of maraviroc and darunavir/ritonavir was inferior to a three-drug regimen of tenofovir/emtricitabine and darunavir/ritonavir in antiretroviral-naive adults.
PMCID: PMC4856180  PMID: 26854810
darunavir; emtricitabine; HIV-1; maraviroc; nucleos(t)ide-sparing regimen; tenofovir; treatment-naive
20.  Short Communication: Viral Suppression Is Associated with Increased Likelihood of Colorectal Cancer Screening Among Persons Living with HIV/AIDS 
With improved survival and aging, more persons living with HIV/AIDS (PLWHA) are at risk for colorectal cancer (CRC). This retrospective longitudinal study evaluated patient characteristics associated with CRC screening in our HIV cohort. Patients were followed beginning at age 50 years during a study period from January 1, 2003 to December 31, 2010 (n=265). During a median follow-up time of 1.7 years, only 30% of patients underwent CRC screening. The majority of screened patients received endoscopic screening (colonoscopy, 86%; sigmoidoscopy, 8%); among these patients, results were available for 68/75, and adenomatous polyps were found in 13%. No cases of CRC were reported. Among unscreened patients, only 23% had an external primary care provider, indicating an HIV provider was the expected source for CRC screening referral in the majority. Patients with time-varying suppressed HIV viral load were more likely to receive screening (HRadjusted=1.74; 95% CI: 1.05–2.87), independent of CD4 count. Our findings suggest HIV providers are more likely to address non-HIV-related healthcare maintenance when HIV is controlled. In addition, a significant number of neoplastic lesions are likely being missed in PLWHA who have not been screened for CRC. Provision of evidence-based preventive care in addition to HIV care is required for the aging population of PLWHA.
PMCID: PMC4426328  PMID: 25435340
21.  A 48-week randomized phase 2b study evaluating cenicriviroc versus efavirenz in treatment-naive HIV-infected adults with C-C chemokine receptor type 5-tropic virus 
AIDS (London, England)  2016;30(6):869-878.
To compare the efficacy, safety, and anti-inflammatory effects of cenicriviroc (CVC), an oral, once-daily C-C chemokine receptor types 5 and 2 antagonist, with those of efavirenz (EFV) in treatment-naive, HIV-1-infected adults.
A 48-week, randomized, double-blind, double-dummy phase 2b trial at 43 institutions (USA and Puerto Rico).
Study participants (HIV-1 RNA ≥1000 copies/ml, CD4+ cell count ≥200 cells/μl, C-C chemokine receptor type 5-tropic virus) were randomized 2 : 2 : 1 to CVC 100 mg (CVC100), CVC 200 mg (CVC200), or EFV 600 mg, each administered with emtricitabine/tenofovir disoproxil fumarate. Key end points were virologic success (HIV-1 RNA <50 copies/ml) at week 24 (primary) and week 48 (secondary), safety/tolerability at weeks 24 and 48. Study sites and patients remained blinded until week 48.
A total of 143 patients were randomized (CVC100, n = 59; CVC200, n = 56; EFV, n = 28). Virologic success was obtained at week 24 in 76, 73, and 71% of study participants for CVC100, CVC200, and EFV, respectively (all P > 0.05 versus EFV), and at week 48 in 68, 64, and 50%, respectively (all P > 0.05 versus EFV). Resistance mutations emerged in five and zero CVC and EFV-treated study participants, respectively. Virologic nonresponse and nucleoside reverse transcriptase inhibitor resistance decreased when CVC minimum plasma concentration was at least 47.8 ng/ml. Treatment-related adverse events of at least grade 2 and discontinuations because of adverse events were less frequent in CVC-treated study participants. Total and low-density lipoprotein cholesterol decreased with CVC, but increased with EFV. C-C chemokine ligand type 2 (CCL2) (aka monocyte chemotactic protein-1) increased in a dose-dependent manner, whereas soluble CD14 levels decreased with CVC.
CVC showed efficacy and favorable safety in treatment-naive HIV-1-infected study participants, supporting selection of CVC200 for phase 3 studies.
Trial registration:
PMCID: PMC4794136  PMID: 26636929
antiretroviral; C-C chemokine receptor type 2 antagonist; C-C chemokine receptor type 5 antagonist; cenicriviroc; HIV-1; randomized controlled trial
22.  Injection drug use and Hepatitis C as risk factors for mortality in HIV-infected individuals: the Antiretroviral Therapy Cohort Collaboration 
HIV-infected individuals with a history of transmission via injection drug use (IDU) have poorer survival than other risk groups. The extent to which higher rates of hepatitis C (HCV) infection in IDU explain survival differences is unclear.
Adults who started antiretroviral therapy (ART) between 2000-2009 in 16 European and North American cohorts with >70% complete data on HCV status were followed for 3 years. We estimated unadjusted and adjusted [for age, sex, baseline CD4 count and HIV-1 RNA, AIDS diagnosis prior to ART, and stratified by cohort] mortality hazard ratios (HR) for IDU (versus non-IDU) and for HCV-infected (versus HCV-uninfected).
Of 32,703 patients 3,374 (10%) were IDU; 4,630 (14%) HCV+; 1,116 (3.4%) died. Mortality was higher in IDU compared with non-IDU (adjusted HR 2.71; 95% CI 2.32,3.16) and in HCV+ compared with HCV− (2.65; 2.31,3.04). The effect of IDU was substantially attenuated (1.57; 1.27,1.94) after adjustment for HCV, while attenuation of the effect of HCV was less substantial (2.04; 1.68,2.47) after adjustment for IDU. Both IDU and HCV were strongly associated with liver-related mortality (10.89; 6.47,18.3 for IDU and 14.0; 8.05,24.5 for HCV) with greater attenuation of the effect of IDU (2.43; 1.24,4.78) than for HCV (7.97; 3.83,16.6). Rates of CNS, respiratory and violent deaths remained elevated in IDU after adjustment for HCV.
A substantial proportion of the excess mortality in HIV-infected IDU is explained by HCV co-infection. These findings underscore the potential impact on mortality of new treatments for HCV in HIV-infected people.
PMCID: PMC4506784  PMID: 25848927
HIV-1; Hepatitis C virus; injection drug use; antiretroviral therapy; cohort study; mortality
23.  Stable Phenotypic Changes of the Host T Cells Are Essential to the Long-Term Stability of Latent HIV-1 Infection 
Journal of Virology  2015;89(13):6656-6672.
The extreme stability of the latent HIV-1 reservoir in the CD4+ memory T cell population prevents viral eradication with current antiretroviral therapy. It has been demonstrated that homeostatic T cell proliferation and clonal expansion of latently infected T cells due to viral integration into specific genes contribute to this extraordinary reservoir stability. Nevertheless, given the constant exposure of the memory T cell population to specific antigen or bystander activation, this reservoir stability seems remarkable, unless it is assumed that latent HIV-1 resides exclusively in memory T cells that recognize rare antigens. Another explanation for the stability of the reservoir could be that the latent HIV-1 reservoir is associated with an unresponsive T cell phenotype. We demonstrate here that host cells of latent HIV-1 infection events were functionally altered in ways that are consistent with the idea of an anergic, unresponsive T cell phenotype. Manipulations that induced or mimicked an anergic T cell state promoted latent HIV-1 infection. Kinome analysis data reflected this altered host cell phenotype at a system-wide level and revealed how the stable kinase activity changes networked to stabilize latent HIV-1 infection. Protein-protein interaction networks generated from kinome data could further be used to guide targeted genetic or pharmacological manipulations that alter the stability of latent HIV-1 infection. In summary, our data demonstrate that stable changes to the signal transduction and transcription factor network of latently HIV-1 infected host cells are essential to the ability of HIV-1 to establish and maintain latent HIV-1 infection status.
IMPORTANCE The extreme stability of the latent HIV-1 reservoir allows the infection to persist for the lifetime of a patient, despite completely suppressive antiretroviral therapy. This extreme reservoir stability is somewhat surprising, since the latently HIV-1 infected CD4+ memory T cells that form the structural basis of the viral reservoir should be exposed to cognate antigen over time. Antigen exposure would trigger a recall response and should deplete the reservoir, likely over a relatively short period. Our data demonstrate that stable and system-wide phenotypic changes to host cells are a prerequisite for the establishment and maintenance of latent HIV-1 infection events. The changes observed are consistent with an unresponsive, anergy-like T cell phenotype of latently HIV-1 infected host cells. An anergy-like, unresponsive state of the host cells of latent HIV-1 infection events would explain the stability of the HIV-1 reservoir in the face of continuous antigen exposure.
PMCID: PMC4468477  PMID: 25878110
24.  Aberrant Drug-Related Behaviors: A qualitative analysis of medical record documentation in patients referred to an HIV/Chronic pain clinic 
Pain medicine (Malden, Mass.)  2014;15(10):1724-1733.
Due to rising rates of opioid addiction and overdose among individuals on chronic opioid therapy, aberrant drug related behaviors (ADRBs) are an important and challenging issue. Our objective was to qualitatively investigate the documentation of ADRBs in the medical record.
Manually abstracted provider notes from an HIV primary care clinic were analyzed using content analysis methods..
Categories of ADRBs identified included patients requesting opioids, obtaining non-prescribed opioids, and becoming emotional about opioids. We also identified several types of provider language used when documenting ADRBs, including purely descriptive language, and emotional language such as labeling, frustration, and concern; and responses such as setting conditions for opioid prescription and action-oriented language.
The impact of including emotional language in the medical record is unknown. Development of instruments that can be used to facilitate ADRB documentation, as well as evidence-based approaches to addressing ADRBs, is needed.
PMCID: PMC4208944  PMID: 25138608
HIV; aberrant behavior; opioid; misuse
25.  Routine Depression Screening in an HIV Clinic Cohort Identifies Patients with Complex Psychiatric Co-morbidities Who Show Significant Response to Treatment 
AIDS and behavior  2013;17(8):2781-2791.
This study described characteristics, psychiatric diagnoses and response to treatment among patients in an outpatient HIV clinic who screened positive for depression. Depressed (25 %) were less likely to have private insurance, less likely to have suppressed HIV viral loads, had more anxiety symptoms, and were more likely to report current substance abuse than not depressed. Among depressed, 81.2 % met diagnostic criteria for a depressive disorder; 78 % for an anxiety disorder; 61 % for a substance use disorder; and 30 % for co-morbid anxiety, depression, and substance use disorders. Depressed received significantly more treatment for depression and less HIV primary care than not depressed patients. PHQ-9 total depression scores decreased by 0.63 from baseline to 6-month follow-up for every additional attended depression treatment visit. HIV clinics can routinely screen and treat depressive symptoms, but should consider accurate psychiatric diagnosis as well as co-occurring mental disorders.
PMCID: PMC4559144  PMID: 23086427
Depression; HIV; Clinic; Treatment; Cohort

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