Excess heart age in adult outpatients in routine HIV care.

Objective: Cardiovascular disease (CVD) is a common cause of morbidity and mortality among persons living with HIV (PLWH). We used individual cardiovascular risk factor profiles to estimate heart age for PLWH in medical care in the United States.

Design: Cross-sectional analyses of HIV Outpatient Study (HOPS) data METHODS:: Included in this analysis were participants aged 30-74 years, without prior CVD, with at least two HOPS clinic visits during 2010-2017, at least 1-year of follow-up, and available covariate data.

Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies.

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes.

Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes.

Cardiovascular Disease Risk Prediction in the HIV Outpatient Study.

Background:  Cardiovascular disease (CVD) risk prediction tools are often applied to populations beyond those in which they were designed when validated tools for specific subpopulations are unavailable.

Methods:  Using data from 2283 human immunodeficiency virus (HIV)-infected adults aged ≥18 years, who were active in the HIV Outpatient Study (HOPS), we assessed performance of 3 commonly used CVD prediction models developed for general populations: Framingham general cardiovascular Risk Score (FRS), American College of Cardiology/American Heart Association Pooled Cohort equations (PCEs), and Systematic COronary Risk Evaluation (SCORE) high-risk equation, and 1 model developed in HIV-infected persons: the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation. C-statistics assessed model discrimination and the ratio of expected to observed events (E/O) and Hosmer-Lemeshow χ P value assessed calibration.

Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study.

Background: Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved renal and bone safety compared with TDF-containing regimens. We report the 48 week safety and efficacy of a once-daily single tablet regimen of elvitegravir 150 mg (E), cobicistat 150 mg (C), emtricitabine 200 mg (F), and TAF 10 mg (E/C/F/TAF) in HIV-1-infected patients with mild to moderate renal impairment.

Methods: We enrolled virologically suppressed HIV-1-infected subjects with estimated creatinine clearance (CrCl) 30-69 mL/min in a single-arm, open-label study to switch regimens to E/C/F/TAF.

High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART.

Statin Use Is Associated With Incident Diabetes Mellitus Among Patients in the HIV Outpatient Study.

Introduction: Statin therapy is effective in the prevention of cardiovascular disease in the general population but has been shown to modestly increase the risk for incident diabetes mellitus (DM).

Methods: We analyzed incident DM in HIV Outpatient Study (HOPS) participants followed at 8 HIV clinic sites during 2002-2011, comparing rates among those who initiated statin therapy during that period with those who did not. Using Cox proportional hazards models, we examined the association between cumulative years of statin exposure and the risk of developing DM, after controlling for age, sex, race/ethnicity, antiretroviral history, prevalent hepatitis C, body mass index, and cumulative exposure to protease inhibitor therapy.

Provider compliance with guidelines for management of cardiovascular risk in HIV-infected patients.

Introduction: Compliance with National Cholesterol Education Program Adult Treatment Panel III (NCEP) guidelines has been shown to significantly reduce incident cardiovascular events. We investigated physicians' compliance with NCEP guidelines to reduce cardiovascular disease (CVD) risk in a population infected with HIV.

Methods: We analyzed HIV Outpatient Study (HOPS) data, following eligible patients from January 1, 2002, or first HOPS visit thereafter to calculate 10-year cardiovascular risk (10yCVR), until September 30, 2009, death, or last office visit.

Disparities in prevalence of key chronic diseases by gender and race/ethnicity among antiretroviral-treated HIV-infected adults in the US.

Background: Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioural risk factors, advanced HIV disease or complications from extended use of combination antiretroviral therapy (cART), but recent comparative data are limited.

Methods: We studied HIV-infected adult patients in care during 2006-2010 who had been prescribed ≥ 6 months of cART. We analysed the prevalence of selected key chronic conditions and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity.

A pilot study to assess inflammatory biomarker changes when raltegravir is added to a virologically suppressive HAART regimen in HIV-1-infected patients with limited immunological responses.

Background: Despite successful suppression of HIV-1 with HAART, some patients do not have robust immunological recovery. Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities.

Methods: We conducted a pilot study of 30 HIV-1-infected patients with undetectable viral loads and poor CD4(+) T-cell responses on long-term stable HAART to assess whether the addition of raltegravir would have an effect on biomarkers of chronic inflammation.

Effect of HIV-1 infection and sex on the cellular pharmacology of the antiretroviral drugs zidovudine and lamivudine.

The cellular pharmacology of zidovudine (ZDV) and lamivudine (3TC) in vivo is not completely understood. This prospective longitudinal study investigated the relationship between HIV-1 serostatus, sex, race, and time on therapy with intracellular and plasma ZDV and 3TC concentrations. Of 20 HIV-seronegative and 23 HIV-seropositive volunteers enrolled, 16 (8 women) and 21 (5 women) completed all 12 study days, respectively.

The associations among coping, nadir CD4+ T-cell count, and non-HIV-related variables with health-related quality of life among an ambulatory HIV-positive patient population.

Purpose: We investigated HRQoL among HIV-positive outpatients from October, 2006-December, 2007, incorporating medical chart review, and a survey of coping styles.

Methods: Consented HIV-positive patients receiving medical care at University of Colorado Denver, with HAART as first antiretroviral regimen, completed the MOS-HIV and Brief COPE survey instruments. Linear regression identified a priori factors hypothesized to be associated with the MOS-HIV composite mental and physical health scores (MHS, PHS).

Factors associated with initiation of prolonged analgesic use among patients in the HIV Outpatient Study (HOPS).

Background: Analgesic use is common but remains poorly described among human immunodeficiency virus (HIV)-infected persons in the highly active antiretroviral therapy era.

Methods: We studied HIV Outpatient Study participants during 1996 to 2008. We used Cox proportional hazards regression to assess variables associated with initiation of prolonged analgesia (≥90 consecutive days of analgesics); logistic regression to explore variables associated with initiation of prolonged opioid analgesia among those taking any prolonged analgesia; and linear regression to determine temporal trends in prolonged analgesia.

Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study.

Background: Traditional cardiovascular disease (CVD) risk factors, human immunodeficiency virus (HIV) infection, and antiretroviral (ARV) agents have been associated with CVD events in HIV-infected patients. We investigated the association of low CD4(+) T lymphocyte cell count with incident CVD in a cohort of outpatients treated in 10 HIV specialty clinics in the United States.

Methods: We studied patients who were under observation from 1 January 2002 (baseline), categorized them according to National Cholesterol Education Program guidelines into 10-year cardiovascular risk score (10-y CVR) groups , and observed them until CVD event, death, last HIV Outpatient Study contact, or 30 September 2009.

AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study.

Objectives: To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era.

Design: A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S.

Antiretroviral treatment interruptions and risk of non-opportunistic diseases.

Structured treatment interruptions have been studied as a strategy to reduce antiretroviral toxicities and expenditures in the treatment of HIV-infected individuals. Paradoxically, in addition to the increased incidence of death and opportunistic infections, these interruptions in therapy have resulted in the development of a number of non-opportunistic diseases, including cardiovascular events, renal insufficiency, hepatic failure, and non-AIDS-defining malignancies. Hypotheses regarding these findings suggest that the augmented stimulation of the host response to unabated viral replication may contribute to these comorbidities.

Initiation of antiretroviral therapy at CD4 cell counts >/=350 cells/mm3 does not increase incidence or risk of peripheral neuropathy, anemia, or renal insufficiency.

Background: US guidelines recommend deferring initiation of highly active antiretroviral therapy (HAART) for most patients with CD4 counts >350 cells/mm in part because of concerns about antiretroviral toxicity.

Methods: Incidence rates of peripheral neuropathy, anemia, and renal insufficiency in a cohort of 2165 patients followed more than 3 years (mean) were analyzed in multivariate Cox proportional hazards models by CD4 cell counts at initiation of HAART. A nested cohort of 895 patients restricted to study participants who did or did not start HAART within a CD4 cell count stratum were also compared.

HIV-associated adipose redistribution syndrome (HARS): definition, epidemiology and clinical impact.

A segment of the HIV infected population develops abnormal and excessive accumulation of adipose tissue in the trunk, including accumulation of visceral (deep abdominal) adipose tissue. This condition, known as HIV-related adipose redistribution syndrome (HARS), may also be accompanied by fat accumulation in the upper back/neck (dorsocervical region) and/or depletion of subcutaneous adipose tissue from the abdomen, face, limbs, or buttocks. HARS is estimated to occur in up to 32% of patients and is associated with health risks similar to those of metabolic syndrome.

HIV-associated adipose redistribution syndrome (HARS): etiology and pathophysiological mechanisms.

Human immunodeficiency virus (HIV)-associated adipose redistribution syndrome (HARS) is a fat accumulation disorder characterized by increases in visceral adipose tissue. Patients with HARS may also present with excess truncal fat and accumulation of dorsocervical fat ("buffalo hump"). The pathophysiology of HARS appears multifactorial and is not fully understood at present.

Effects of esomeprazole on the pharmacokinetics of atazanavir and fosamprenavir in a patient with human immunodeficiency virus infection.

The effects of proton pump inhibitors on the pharmacokinetics of atazanavir and amprenavir (administered as fosamprenavir) were rigorously evaluated in healthy volunteers in two studies, but formal studies in persons infected with human immunodeficiency virus (HIV) are lacking. We describe a 65-year-old man with HIV who underwent a 12-hour intensive pharmacokinetic study while receiving esomeprazole with atazanavir-ritonavir and subsequently, an 8-hour study while receiving esomeprazole with fosamprenavir-ritonavir. Consistent with the data in healthy volunteers, a major interaction between esomeprazole and atazanavir-ritonavir was observed in this patient-marked reductions in atazanavir trough plasma concentration and in the area under the concentration-time curve from 0-24 hours-whereas an interaction between esomeprazole and fosamprenavir-ritonavir was not apparent in this patient.

96-week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures.

Background: In BMS Study 045, once-daily (QD) atazanavir/ritonavir (ATV/RTV) demonstrated comparable efficacy and safety to twice-daily (BID) lopinavir/ritonavir (LPV/RTV) over 48 weeks in treatment-experienced patients. Results of extended follow-up to 96 weeks are presented.

Methods: BMS Study 045 was an open-label, randomized, multi-national trial of HIV-infected patients with virologic failure on two or more prior HAART regimens designed to evaluate the efficacy and safety of ATV/RTV (300/100 mg) QD and LPV/RTV (400/100 mg) BID, each with tenofovir (300 mg) QD and one nucleoside reverse transcriptase inhibitor.

Redefining lipodystrophy syndrome: risks and impact on clinical decision making.

Lipodystrophy syndrome comprises several conditions (lipoatrophy; lipohypertrophy; mixed syndrome, often associated with dyslipidemia; and insulin resistance). These conditions, though sometimes occurring together, may occur independently, suggesting a complex, multifactorial cause. To elucidate the relative contribution of risk factors of drug, disease, and host to fat redistribution, large epidemiologic studies using multivariate analysis were reviewed.

Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures.

Objective: To evaluate atazanavir/ritonavir (ATV/RTV) (300/100 mg) once daily, atazanavir/saquinavir (ATV/SQV) (400/1200 mg) once daily, and lopinavir/ritonavir (LPV/RTV) (400/100 mg) twice daily, each with tenofovir (300 mg) once daily and a nucleoside reverse transcriptase inhibitor in treatment-experienced HIV-infected patients.

Methods: Randomized, open-label, 48-week multicenter trial of 358 randomized adult patients who had failed two or more prior HAART regimens with baseline HIV RNA > or = 1000 copies/ml and CD4 cell count > or = 50 x 10(6) cells/l.

Results: The primary efficacy endpoint [plasma HIV RNA reduction assessed by time-averaged difference (TAD)] was similar for ATV/RTV and LPV/RTV [TAD 0.