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 U.S. DESIGN: Cross-sectional analyses of HIV Outpatient Study (HOPS) data METHODS:: Included in this analysis were participants aged 30-74 years, without prior CVD, >/= 2 HOPS clinic visits during 2010-2017, >/=1 year of follow-up, and available covariate data. We calculated age and race/ethnicity-adjusted heart age and excess heart age (chronological age minus heart age), using a Framingham risk score-based model. RESULTS: We analyzed data from 2467 men and 619 women (mean chronologic age 49.3 and 49.1 years, and 23.6% and 54.6% Non-Hispanic/Latino black, respectively). Adjusted excess heart age was 11.5 y (95% confidence interval, 11.1-12.0) among men and 13.1 y (12.0-14.1) among women. Excess heart age was seen among all age groups beginning with persons aged 30-39 y (men, 7.8 [6.9-8.8]; women, 7.7 [4.9-10.4]), with the highest excess heart age among participants aged 50-59 y (men, 13.7 y [13.0-14.4]; women, 16.4 y [14.8-18.0]). More than 50% of participants had an excess heart age of >/=10 years. CONCLUSIONS: Excess heart age is common among PLWH, begins in early adulthood, and impacts both women and men. Among PLWH, CVD risk factors should be addressed early and proactively. Routine use of the heart age calculator may help optimize CVD risk stratification and facilitate interventions for aging PLWH.

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 2,283 HIV-infected adults aged ≥18 years, who were active in the HIV Outpatient Study (HOPS), we assessed performance of three 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 (PCE), and Systematic COronary Risk Evaluation (SCORE) high-risk equation, and one 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 chi2 P-value assessed calibration. RESULTS: From January 2002 through September 2013, 195 (8.5%) HOPS participants experienced an incident CVD event in 15,056 person-years. The FRS demonstrated moderate discrimination and was well calibrated (C-statistic: 0.66, E/O: 1.01, P=0.89). The PCE and D:A:D risk equations demonstrated good discrimination but were less well calibrated (C-statistics: 0.71, 0.72 and E/O: 0.88, 0.80, respectively; P<0.001 for both), while SCORE performed poorly (C-statistic: 0.59, E/O: 1.72, P =0.48). CONCLUSION: Only the FRS accurately estimated risk of CVD events, while PCE and D:A:D underestimated risk. Although these models could potentially be used to rank U.S. HIV-infected individuals at higher or lower risk for CVD, the models may fail to identify substantial numbers of HIV-infected persons with elevated CVD risk who could potentially benefit from additional medical treatment.

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. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4+ cell count 464 cells/mm3, 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.

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. We also adjusted for propensity scores to account for residual confounding by indication. RESULTS: Of 4692 patients analyzed, 590 (12.6%) initiated statin therapy and 355 (7.2%) developed DM. Incident DM was independently associated with statin therapy (adjusted hazard ratio, 1.14 per year of statin use), as well as older age, Hispanic/Latino ethnicity, non-Hispanic/Latino black race, antiretroviral-naive status, prevalent hepatitis C, and body mass index ≥30 kg/m (P < 0.05 for all). The association of statin use with incident DM was similar in the model adjusted for propensity score. CONCLUSIONS: Statin use was associated with a modestly increased risk of incident DM in an HIV-infected population, similar to existing data for the general population. HIV-infected patients should be monitored for glucose intolerance, but statins should not be withheld if clinically indicated for cardiovascular disease risk reduction.

BACKGROUND: Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioral 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 analyzed the prevalence of selected key chronic conditions, and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity. RESULTS: Of the 3,166 HIV-infected patients (median age, 47 years; CD4+ cell count, 496 cells/mm(3); duration of cART use, 6.8 years), 21% were female, 57% were non-Hispanic white, and over half were current or former tobacco smokers. The five most frequent conditions among women (median age, 45 years) were dyslipidemia (67.3%), hypertension (57.4%), obesity (31.7%), viral hepatitis B or C coinfection (29.0%), and low HDLc (27.3%). The five most frequent conditions in men (median age, 47 years) were dyslipidemia (81.2%), hypertension (54.4%), low HDLc (41.1%), elevated triglycerides (32.3%), and elevated non-HDLc (26.8%). In multivariable analyses, Hispanic patients had higher prevalence of obesity and diabetes than white patients; black patients had higher prevalence of obesity and hypertension but lower rates of lipid abnormalities. Of all patients, 73.7% of women and 66.8% of men had polymorbidity, with no evidence of disparities by race/ethnicity. CONCLUSIONS: Among contemporary cART-treated HIV-infected adults, chronic conditions and polymorbidity were common, underscoring the importance of chronic disease prevention and management among aging HIV-infected patients.

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. We calculated rates of incident CVD events and identified associated baseline risk factors using Cox proportional hazard models. We also performed a nested case-control study to examine the association of latest CD4(+) cell count with CVD events. RESULTS: Among 2005 patients, 148 experienced incident CVD events. CVD incidence increased steadily from 0.4 to 3.0 events per 100 person-years from lowest to highest 10-y CVR group (P < .001). In multivariable Cox analyses adjusted for 10-y CVR, CD4(+) cell count <350 cells/mm(3) was associated with incident CVD events (hazard ratio, 1.58 [95% confidence interval, 1.09-2.30], compared with >500 cells/mm(3)), suggesting an attributable risk of approximately 20%. In the multivariable case-control analyses, traditional CVD risk factors and latest CD4(+) cell count <500 cells/mm(3), but not cumulative use of ARV class or individual drugs, were associated with higher odds of experiencing CVD events. CONCLUSION: CD4(+) count <500 cells/mm(3) is an independent risk factor for incident CVD, comparable in attributable risk to several traditional CVD risk factors in the HIV Outpatient Study cohort.

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. HIV clinics. METHODS: We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994-2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period. RESULTS: Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/mul) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994-1997, 1998-2002, and 2003-2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003-2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% opportunistic illness events occurred at CD4 cell counts at least 200 cells/mul. CONCLUSIONS: Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003-2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/mul.