Veterans Aging Cohort Study Index Research Articles

Veterans Aging Cohort Study Index as a Marker of Bone Disease in HIV-Infected Patients.

People living with human immunodeficiency virus (HIV) infection have higher risk of low bone mineral density (BMD) and fragility fracture than general population. The aim of our retrospective study was to explore if HIV-specific Veterans Aging Cohort Study (VACS) Index and its specific components could help identify patients at risk for low BMD. A total of 195 HIV-infected patients with dual-energy X-ray absorptiometry (DXA) scan between 2007 and 2014 were included and DXA scan results were used to classify patients with osteopenia. VACS Index was calculated for all patients using laboratory values closest to the date of DXA scan. Logistic regression was used to assess the association between VACS Index score or individual components of VACS Index with the presence of low BMD after adjusting for confounding variables. A total of 109 (56%) patients were diagnosed with low BMD. VACS Index score was significantly associated with low BMD, with the odds of low BMD increasing 1.21 times for each 10 unit increase in VACS Index score [confidence interval (95% CI) 1.03-1.42; p = .02]. The two groups differed significantly on patient weights, proportion of white patients, and hepatitis C-coinfected patients. After adjusting for white race and weight, hepatitis C coinfection was significantly associated with increased risk of low BMD (odds ratio 24.4; 95% CI 7.45-80.16). VACS Index score, previously demonstrated to be a marker of frailty in HIV-infected patients, is significantly associated with risk of low BMD and could be used to develop a prediction tool to screen for low BMD in resource-limited setting where DXA scans are not easily available.

Screening tools for targeted comprehensive geriatric assessment in HIV-infected patients 50 years and older.

Many people living with HIV (PLWH) are aging with geriatric syndromes, but few undergo comprehensive geriatric assessment (CGA) due to limited resources. Our study evaluates tools to identify aging PLWH who may forego CGA. We conducted a cross-sectional study on 357 PLWH ≥50 years old at the Red Cross, Thailand. Tools evaluated were the Veterans Aging Cohort Study Index (VACSI) and G-8, which is predictive among older cancer patients. CGA consists of eight tests: history of fall within 12 months, timed-up-and-go test (TUG), activities of daily living (ADL), instrumental ADL (IADL), Montreal cognitive assessment (MoCA), Thai depression scale (TDS), mini nutritional assessment (MNA), and HIV symptom index (HSI). We considered ≥2 impaired domains on CGA to be abnormal results. Forty-nine percent (n = 175) had ≥2 impaired domains on CGA. Few participants had experienced a fall (11%) or abnormal TUG/ADL/IADL (<2%), and only MoCA/TDS/MNA/HSI were analyzed. A VACSI < 17 produces 85% sensitivity (Se) and 30% specificity (Sp) (area under the ROC curve [AUC] = 63, 95%CI 58–69) and G-8 > 15.5 produces 90%Se and 33%Sp (AUC = 74, 95%CI 69–79) in identifying patients with <2 impaired domains. A G-8 > 13.5 produces 91%Se and 77%Sp (AUC = 89, 95%CI 86–92) in ruling out abnormal nutrition. Patients with VACSI < 17 and G-8 > 15.5 may forego CGA due to low likelihood of abnormal cognition, mood, nutrition, or symptom burden.

HIV Disease Severity Is Sensitive to Temporal Changes in Alcohol Use: A National Study of VA Patients With HIV.

Alcohol use influences HIV disease severity through multiple mechanisms. Whether HIV disease severity is sensitive to changes in alcohol use among people with HIV (PWH) is understudied. National Veterans Health Administration. Pairs of AUDIT-C screens within 9-15 months (February 1, 2008-September 30, 2014) were identified among PWH from the Veterans Aging Cohort Study (VACS). Initial and follow-up VACS Index 2.0 pairs obtained 0-270 days after initial and follow-up AUDIT-Cs, respectively, determined change in VACS Index 2.0, a composite HIV severity measure. Change in VACS Index 2.0 was regressed on AUDIT-C change scores (-12 to +12) adjusted for demographics, initial VACS Index 2.0, and days between VACS Index measures. Among 23,297 PWH (76,202 observations), most had no (51%) or low-level (38%) alcohol use initially. Most (54%) had no subsequent change; 21% increased and 24% decreased drinking. Initial VACS Index 2.0 scores ranged from 0 to 134, change scores ranged from -65 to +73, with average improvement of 0.76 points (SD 9.48). AUDIT-C change was associated with VACS Index 2.0 change (P < 0.001). Among those with stable alcohol use (AUDIT-C change ≤ │1│ point), VACS Index 2.0 improvements ranged 0.36-0.60 points. For those with maximum AUDIT-C increase (change from 0 to 12), VACS Index 2.0 worsened 3.74 points (95% CI: -4.71 to -2.78); for those with maximum AUDIT-C decrease (change from 12 to 0), VACS Index 2.0 changed minimally [-0.60 (95% CI: -1.43 to 0.23)]. In this national sample, improvement in HIV severity was generally greatest among those with stable alcohol use (primarily those with no use).

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Inflammatory Biomarkers in Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and HIV/HCV Coinfection.

Inflammation in human immunodeficiency virus (HIV)-infected patients is associated with poorer health outcomes. Whether inflammation as measured by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) adds information to existing prognostic indices is not known. We analyzed data from 2000 to 2012 in the Veterans Aging Cohort Study (VACS), overall and stratified by HIV/hepatitis C virus status (n = 89 786). We randomly selected a visit date at which all laboratory values of interest were available within 180 days; participants with HIV received at least 1 year of antiretroviral therapy. We followed patients for (1) mortality and (2) hepatic decompensation (HD) and analyzed associations using Cox regression, adjusted for a validated mortality risk index (VACS Index 2.0). In VACS Biomarker Cohort, we considered correlation with biomarkers of inflammation: interleukin-6, D-dimer, and soluble CD-14. Neutrophil-to-lymphocyte ratio and PLR demonstrated strong unadjusted associations with mortality (P < .0001) and HD (P < .0001) and were weakly correlated with other inflammatory biomarkers. Although NLR remained statistically independent for mortality, as did PLR for HD, the addition of NLR and PLR to the VACS Index 2.0 did not result in significant improvement in discrimination compared with VACS Index 2.0 alone for mortality (C-statistic 0.767 vs 0.758) or for HD (C-statistic 0.805 vs 0.801). Neutrophil-to-lymphocyte ratio and PLR were strongly associated with mortality and HD and weakly correlated with inflammatory biomarkers. However, most of their association was explained by VACS Index 2.0. Addition of NLR and PLR to VACS 2.0 did not substantially improve discrimination for either outcome.

Geriatric Syndromes in Older Adults Living with HIV and Cognitive Impairment.

Nearly half of the population living with human immunodeficiency virus (HIV) in the United States is now older than 50 years with at least 6% over age 65. Between 35% and 50% live with mild to moderate cognitive impairment. Older persons living with HIV (PLWH) also have a substantial burden of HIV-associated non-acquired immunodeficiency syndrome medical conditions and are at risk for frailty, geriatric syndromes, and early mortality compared with HIV-uninfected peers. We sought to define the magnitude of geriatric conditions and multimorbidity in PLWH older than 60 years who are living with symptomatic cognitive impairment. In a subset of participants, we examined associations between these geriatric conditions. Retrospective cohort study. HIV Elders Study at the University of California, San Francisco, Memory and Aging Center. Participants were HIV infected, virally suppressed, 60 years or older, and clinically diagnosed with mild neurocognitive disorder (MND). We conducted standardized assessment of geriatric conditions and everyday function and investigated multimorbidity burden using the Veterans Aging Cohort Study (VACS) index. Among 141 older PLWH with MND, 58% report incontinence, 55% meet criteria for pre-frailty, and a substantial proportion report dependence with instrumental activities of daily living (52%) or activities of daily living (41%). The mean VACS index score is 33 (standard deviation = 14), suggesting a 13.8% 5-year all-cause mortality risk. Older PLWH with symptomatic cognitive impairment carry a substantial burden of other geriatric conditions. Our work supports the need for comprehensive geriatric systems of care for cognitively impaired individuals aging with HIV. J Am Geriatr Soc 67:1913-1916, 2019.

Albumin, white blood cell count, and body mass index improve discrimination of mortality in HIV-positive individuals.

Despite viral suppression and immune response on antiretroviral therapy, people with HIV infection experience excess mortality compared with uninfected individuals. The Veterans Aging Cohort Study (VACS) Index incorporates clinical biomarkers of general health with age, CD4 cell count, and HIV-1 RNA to discriminate mortality risk in a variety of HIV-positive populations. We asked whether additional biomarkers further enhance discrimination. Using patients from VACS for development and from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for validation, we obtained laboratory values from a randomly selected visit from 2000 to 2014, at least 1 year after antiretroviral therapy initiation. Patients were followed for 5-year, all-cause mortality through September 2016. We fitted Cox models with established predictors and added new predictors based on model fit and Harrell's c-statistic. We converted all variables to continuous functional forms and selected the best model (VACS Index 2.0) for validation in ART-CC patients. We compared discrimination using c-statistics and Kaplan-Meier plots. Among 28 390 VACS patients and 12 109 ART-CC patients, 7293 and 722 died, respectively. Nadir CD4, CD8, and CD4 : CD8 ratio did not improve discrimination. Addition of albumin, white blood count, and BMI, improved c-statistics in VACS from 0.776 to 0.805 and in ART-CC from 0.800 to 0.831. Results were robust in all nine ART-CC cohorts, all lengths of follow-up and all subgroups. VACS Index 2.0, adding albumin, white blood count, and BMI to version 1.0 and using continuous variables, provides improved discrimination and is highly transportable to external settings.

HIV-1 coreceptor tropism: A syllogistic connection with The Veterans Aging Cohort Study Index and the CD4/CD8 ratio.

BackgroundThe association between X4 virus and an increased risk of non-AIDS-events has been reported. Morbidity/mortality due to non-AIDS events, which are properly predicted by the CD4/CD8 ratio and VACS index, have become particularly remarkable in HIV-infected patients receiving effective combined antiretroviral therapy (cART).MethodsWe verified the validity of the syllogism: as HIV-tropism (CRT) contributes to the onset of non-AIDS events which are successfully predicted by the CD4/CD8 ratio and VACS index, then CRT correlates with these two variables. The CD4/CD8 ratio and VACS index at baseline and overtime were analyzed according to CRT tested before the first successful cART regimen in newly-diagnosed patients.ResultsPatients with R5 variants had a significantly lower baseline VACS percentage risk [mean (95%CI):18.2%(16.1–20.3) vs 24.3%(18.2–22.5), p = 0.002] and higher baseline CD4/CD8 ratio [mean (95%CI):0.43 (0.38–0.47) vs 0.28 (0.19–0.36), p = 0.002] than non-R5 patients. After an initial drop, VACS increased again in R5 and non-R5 patients and the two trend curves almost overlapped. The CD4/CD8 ratio had an increasing trend in both R5 and non-R5 patients; however, even though non-R5 patients had a greater gain of CD4+, they maintained a lower CD4/CD8 ratio at any time point.ConclusionOur study confirms an association between pre-therapy CRT, CD4/CD8 ratio and VACS. A successful cART regimen positively affects the CD4/CD8 ratio; however, the disadvantage conferred by a non-R5 CRT is maintained overtime. The restoration of VACS in all patients could be directly due to variables included in the VACS calculation and to factors that adversely influence these variables.

Middle-Aged Men With HIV Have Diminished Accelerometry-Based Activity Profiles Despite Similar Lab-Measured Gait Speed: Pilot Study.

BackgroundPeople aging with HIV are living with increased risk for functional decline compared with uninfected adults of the same age. Early preclinical changes in biomarkers in middle-aged individuals at risk for mobility and functional decline are needed.ObjectiveThis pilot study aims to compare measures of free-living activity with lab-based measures. In addition, we aim to examine differences in the activity level and patterns by HIV status.MethodsForty-six men (23 HIV+, 23 HIV−) currently in the MATCH (Muscle and Aging Treated Chronic HIV) cohort study wore a consumer-grade wristband accelerometer continuously for 3 weeks. We used free-living activity to calculate the gait speed and time spent at different activity intensities. Accelerometer data were compared with lab-based gait speed using the 6-minute walk test (6-MWT). Plasma biomarkers were measured and biobehavioral questionnaires were administered.ResultsHIV+ men more often lived alone (P=.02), reported more pain (P=.02), and fatigue (P=.048). In addition, HIV+ men had lower blood CD4/CD8 ratios (P<.001) and higher Veterans Aging Cohort Study Index scores (P=.04) and T-cell activation (P<.001) but did not differ in levels of inflammation (P=.30) or testosterone (P=.83). For all participants, accelerometer-based gait speed was significantly lower than the lab-based 6-MWT gait speed (P<.001). Moreover, accelerometer-based gait speed was significantly lower in HIV+ participants (P=.04) despite the absence of differences in the lab-based 6-MWT (P=.39). HIV+ participants spent more time in the lowest quartile of activity compared with uninfected (P=.01), who spent more time in the middle quartiles of activity (P=.02).ConclusionsAccelerometer-based assessment of gait speed and activity patterns are lower for asymptomatic men living with HIV compared with uninfected controls and may be useful as preclinical digital biomarkers that precede differences captured in lab-based measures.

Biomarkers of Inflammation Correlate With Clinical Scoring Indices in Human Immunodeficiency Virus-Infected Kenyans.

In high-income countries, inflammation has been associated with increased morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals despite treatment with antiretroviral therapy (ART). However, these findings may not be generalizable to low-income settings. In this cross-sectional study, multivariable linear regression was used to compare 28 inflammatory biomarker levels in HIV-infected and -uninfected participants. Correlations between biomarkers and Veterans Aging Cohort Study (VACS) index, Fibrosis-4 (FIB-4) score, and Framingham risk score were assessed. Plasma samples from 304 Kenyans were analyzed. Compared to HIV-uninfected controls, virologically suppressed HIV-infected participants had higher levels of CCL5, CXCL10, fatty acid binding protein (FABP) 2, fas ligand (FASLG), matrix metalloproteinase (MMP) 1, MMP7, soluble CD14 (sCD14), and soluble CD163 (sCD163) and lower MMP9 (P < .01). CD4+/HLA-DR+CD38+ (ρ = 0.32; P < .001), sCD14 (ρ = 0.25; P = .004), and sCD163 (ρ = 0.24; P = .006) were correlated with the VACS index. FABP2 was positively correlated (ρ = 0.29; P = .002), whereas MMP1 (ρ = -.32; P < .001) and MMP2 (ρ = -0.28; P = .002) were inversely correlated with the FIB-4 score. Differences in biomarker levels exist between well-controlled HIV-infected participants on ART and uninfected controls. Some biomarkers are correlated to scoring indices predictive of morbidity and mortality. These biomarkers could serve as prognostic indicators and inform therapeutic development.

A composite of multisystem injury and neurocognitive impairment in HIV infection: association with everyday functioning.

The Veterans Aging Cohort Study (VACS) Index is a composite marker of multisystem injury among HIV-infected persons. We aimed to examine its cross-sectional association with functional outcomes, after considering neurocognitive impairment (NCI) and other well-established correlates of everyday functioning among HIV-infected persons. Participants included 670 HIV-infected adults (ages 18-76; 88% male; 63% non-Hispanic White; median current CD4 = 404cells/mm3; 67% on antiretroviral therapy; AIDS = 63%) enrolled in observational studies at the University of California San Diego HIV Neurobehavioral Research Program. Functional outcomes were assessed via self-report measures of declines in activities of daily living, perceived cognitive symptoms in daily life, and employment status. NCI was assessed via a comprehensive neurocognitive test battery and defined based on established methods. Covariates examined included demographics, HIV disease characteristics not included in the VACS Index, and psychiatric comorbidities. The VACS Index was computed via standard methods and categorized based on its distribution. Results from multivariable regression models showed that both higher VACS Index scores (indicative of worse health) and the presence of NCI were independently associated with declines in activities of daily living, increased cognitive symptoms in daily life, and unemployment. These independent effects remained after adjusting for significant covariates. In conclusion, the VACS Index may be a useful tool for identifying HIV-infected patients at high risk for everyday functioning problems. Considering factors such as NCI, historical HIV disease characteristics, and current mood might be particularly important to enhance the predictive power of the VACS Index for functional status among HIV-infected persons.

Markers of chronic obstructive pulmonary disease are associated with mortality in people living with HIV.

Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected study participants. Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. EXHALE includes 196 PLWH and 165 uninfected smoking-matched study participants who underwent pulmonary function testing and computed tomography (CT) to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the Veterans Aging Cohort Study (VACS) Index, a validated predictor of mortality in HIV. Median follow-up time was 6.9 years; the mortality rate was 2.7/100 person-years among PLWH and 1.7/100 person-years among uninfected study participants (P = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected study participants. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (forced expiratory volume in 1 s/ forced vital capacity <0.7) had 3.1 times the risk of death [hazard ratio 3.1 (95% confidence interval 1.4-7.1)], compared with those without; those with emphysema (>10% burden) had 2.4 times the risk of death [hazard ratio 2.4 (95% confidence interval 1.1-5.5)] compared with those with ≤ 10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power. Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.

Association of Cannabis, Stimulant, and Alcohol use with Mortality Prognosis Among HIV-Infected Men.

Questionnaires over a 9-year study period (2002-2010) were used to characterize cannabis, stimulant, and alcohol use among 3099 HIV-infected men participating in the Veterans Aging Cohort Study (VACS) to determine whether use of these substances is associated with changes in the VACS Index, a validated prognostic indicator for all-cause mortality. At baseline, 18% of participants reported no substance use in the past year, 24% lower risk alcohol use only, 18% unhealthy alcohol use only, 15% cannabis use (with or without alcohol), and 24% stimulant use (with or without alcohol or cannabis). In adjusted longitudinal analyses, cannabis use [β=-0.97 (95% CI -1.93, 0.00), p=0.048] was not associated with mortality risk, while stimulant use [1.08 (0.16, 2.00), p=0.021] was associated with an increased mortality risk, compared to lower risk alcohol use. Our findings show no evidence of a negative effect of cannabis use on mortality risk, while stimulant use was associated with increased mortality risk among HIV-infected men. Interventions to reduce stimulant use in this patient population may reduce mortality.

Long-term alcohol use patterns and HIV disease severity.

We examined the relationship between alcohol use trajectories and HIV disease severity among men and women participating in the Veterans Aging Cohort Study (VACS). Prospective cohort of HIV-infected persons in care at eight US Veterans Health Administration sites. Between 2002 and 2010, we assessed alcohol consumption annually using the alcohol use disorders identification test-consumption (AUDIT-C). HIV disease severity was ascertained using the VACS index, a validated measure of morbidity and all-cause mortality. We examined the relationship between alcohol use and HIV disease severity patterns using joint trajectory modeling. Alcohol use trajectories were validated using phosphatidylethanol - a biomarker of alcohol consumption - measured between 2005 and 2006 among a subset of participants. We examined associations between membership in alcohol use and VACS index trajectories using multinomial regression. Among eligible participants, we identified four alcohol consumption trajectories: abstainers (24% of the sample), lower risk (44%), moderate risk (24%), and higher risk drinkers (8%). Alcohol use trajectories were highly correlated with phosphatidylethanol (Cramér's V = 0.465, P < 0.001): mean concentrations were 4.4, 17.8, 57.7, and 167.6 ng/ml in the abstainer, lower risk, moderate risk, and higher risk groups, respectively. Four VACS index trajectories were identified: low (2%), moderate (46%), high (36%), and extreme (16%). Higher risk drinkers were most common in the extreme VACS index group, and were absent in the low index group. In multivariable analysis, the association between alcohol use and VACS index trajectory membership remained significant (P = 0.002). Alcohol use trajectories characterized by persistent unhealthy drinking are associated with more advanced HIV disease severity among HIV-infected veterans in the United States.

Prevalence and Predictors of Hospitalizations Among HIV-Infected and At-Risk HIV-Uninfected Women.

We evaluated the Veterans Aging Cohort Study (VACS) Index score, an index composed of age, CD4 count, viral load, hemoglobin, Hepatitis C coinfection, Fibrosis Index-4, and estimated glomerular filtration rate, and psychosocial and clinical risk factors for all-cause hospitalization among HIV-infected women on highly active antiretroviral therapy and HIV-uninfected women. Data were collected from 2008 to 2014 from 1585 highly active antiretroviral therapy-experienced HIV infected and 692 uninfected women. Cox proportional hazards regression evaluated predictors of first hospitalization over 2 years. Among HIV-infected women, VACS Index score (per 5 points) [adjusted hazard ratio (aHR) 1.08; 95% confidence interval (CI): 1.06 to 1.11], Centers for Epidemiologic Studies-Depression (CESD) scores ≥16 (aHR 1.61; 95% CI: 1.30 to 1.99), smoking (aHR 1.26; 95% CI: 1.02 to 1.55), abuse history (aHR 1.52; 95% CI: 1.20 to 1.93), diabetes (aHR 1.63; 95% CI: 1.31 to 2.04), and black race (aHR 1.28; 95% CI: 1.03 to 1.59) increased risk of hospitalization. Among HIV-uninfected women, VACS Index score (aHR 1.08; 95% CI: 1.03 to 1.13), CESD scores ≥16 (aHR 1.38; 95% CI: 1.02 to 1.86), diabetes (aHR 2.15; 95% CI: 1.57 to 2.95), and black race (aHR 1.61; 95% CI: 1.15 to 2.24) predicted subsequent hospitalization. Psychosocial and clinical factors were associated with risk of hospitalization independently of the VACS Index score. Additional research on contextual and psychosocial influences on health outcomes among women is needed.

Effects of Therapy with Maraviroc on the Carotid Intima Media Thickness in HIV-1/HCV Co-infected Patients

To evaluate, in human immunodeficiency virus-hepatitis C virus co-infected patients, the impact of C-C chemokine receptor type 5 (CCR5) antagonist maraviroc-based antiretroviral therapy on the carotid intima media thickness and on atheromasic plaques. In this pilot prospective study, 12 HIV-HCV co-infected patients underwent color-Doppler ultrasonography before and 48 weeks after switching to a dual therapy based on maraviroc plus protease inhibitors boosted with ritonavir. Changes of intima media thickness, inflammatory and endothelial adhesion biomarkers levels, Veterans Aging Cohort Study index and Framingham risk score were evaluated. At baseline 11 (91.6%) patients showed pathological ultrasonographic findings. After 48 weeks, two patients showed an amelioration of intima media thickness. Of the remaining patients with plaques, four showed a reduction of the previously diagnosed plaque; no patients worsened. Our data suggest that CCR5 inhibition could reduce the development of atherosclerosis especially in the non-calcific stage and could play an important role in the blockade of atheromasic plaque progression.

White Blood Count, Albumin, and BMI Enhance VACS Index Prognostic Model, but Nadir CD4 and CD8 Metrics Do Not

Background People living with HIV frequently achieve long-term viral suppression necessitating better metrics of disease burden for clinical management and research. The Veterans Aging Cohort Study (VACS) Index predicts hospitalization, mortality, and other outcomes, using routinely available clinical data. We sought to enhance the index by evaluating whether nadir CD4, CD8, CD4/CD8 ratio, white blood count (WBC) or absolute neutrophil count (ANC), albumin, and body mass index (BMI) enhanced prediction. The original index categorized predictors for ease of understanding and calculation of a risk score. We also sought to expand categories and develop a continuous variable model, suitable for use with automated calculation, to provide higher resolution.Methods VACS, includes all HIV infected patients in VA Care. Among those who initiated ART 1996–2013, (excluding any treated for HCV infection), we obtained laboratory values from a randomly selected visit 2000–2014, at least one year after ART initiation. Patients were followed for 5-year, all cause mortality until September 30, 2016. We fit Cox models starting with currently used predictors (age, CD4, HIV-1 RNA, hemoglobin, FIB4, eGFR and HCV status) and decided to include new variables based on model fit, chi-square, strength and significance of individual levels and c-statistic. Functional form for continuous variables was determined graphically. Adequacy of final models was assessed with Kaplan-Meier plots by deciles of risk.ResultsAmong 28,390 patients there were 7,293 deaths (7.2 per 100 person-years) in median 4.1 years of follow-up. Nadir CD4, CD8, CD4:CD8 did not improve prediction. WBC and ANC performed equally but WBC was more widely available. C-statistics improved from 0.776 for the original VACS Index (in this sample) to 0.805.Conclusion Addition of WBC, albumin, and BM enhances utility of the VACS Index as a measure of overall severity of disease both as an outcome for research and for patient monitoring in the clinical setting. Validation in external cohorts is in progress.Disclosures All authors: No reported disclosures.

Veterans Aging Cohort Study Index as a Marker of Bone Disease in HIV-Infected Patients

Veterans Aging Cohort Study Index as a Marker of Bone Disease in HIV-Infected Patients

The impact of prescribed opioids on CD4 cell count recovery among HIV-infected patients newly initiating antiretroviral therapy.

Certain prescribed opioids have immunosuppressive properties, yet their impact on clinically relevant outcomes, including antiretroviral therapy (ART) response among HIV-infected patients, remains understudied. Using the Veterans Aging Cohort Study data, we conducted a longitudinal analysis of 4358 HIV-infected patients initiating ART between 2002 and 2010 and then followed them for 24 months. The primary independent variable was prescribed opioid duration, categorized using pharmacy data as none prescribed, short-term (< 90 days) and long-term (≥ 90 days). Outcomes included CD4 cell count over time. Analyses adjusted for demographics, comorbid conditions, ART type and year of initiation, and overall disease severity [ascertained with the Veterans Aging Cohort Study (VACS) Index]. Sensitivity analyses examined whether effects varied according to baseline CD4 cell count, achievement of viral load suppression, and opioid properties (i.e. dose and known immunosuppressive properties). Compared to those with none, patients with short-term opioids had a similar increase in CD4 cell count (mean rise per year: 74 vs. 68 cells/μL; P = 0.11), as did those with long-term prescribed opioids (mean rise per year: 74 vs. 75 cells/μL; P = 0.98). In sensitivity analysis, compared with no opioids, the effects of short-term prescribed opioids were statistically significant among those with a baseline CD4 cell count ≥ 500 cells/μL (mean rise per year: 52 cells/μL for no opioids vs. 20 cells/μL for short-term opioids; P = 0.04); findings were otherwise unchanged. Despite immunosuppressive properties intrinsic to opioids, prescribed opioids appeared to have no effect on CD4 cell counts over 24 months among HIV-infected patients initiating ART.

Baseline, Time-Updated, and Cumulative HIV Care Metrics for Predicting Acute Myocardial Infarction and All-Cause Mortality.

After adjustment for cardiovascular risk factors and despite higher mortality, those with human immunodeficiency virus (HIV+) have a greater risk of acute myocardial infarction (AMI) than uninfected individuals. We included HIV+ individuals who started combination antiretroviral therapy (cART) in the Veterans Aging Cohort Study (VACS) from 1996 to 2012. We fit multivariable proportional hazards models for baseline, time-updated and cumulative measures of HIV-1 RNA, CD4 counts, and the VACS Index. We used the trapezoidal rule to build the following cumulative measures: viremia copy-years, CD4-years, and VACS Index score-years, captured 180 days after cART initiation until AMI, death, last clinic visit, or 30 September 2012. The primary outcomes were incident AMI (Medicaid, Medicare, and Veterans Affairs International Classification of Diseases-9 codes) and death. A total of 8168 HIV+ individuals (53 861 person-years) were analyzed with 196 incident AMIs and 1710 deaths. Controlling for known cardiovascular risk factors, 6 of the 9 metrics predicted AMI and all metrics predicted mortality. Time-updated VACS Index had the lowest Akaike information criterion among all models for both outcomes. A time-updated VACS Index score of 55+ was associated with a hazard ratio (HR) of 3.31 (95% confidence interval [CI], 2.11-5.20) for AMI and a HR of 31.77 (95% CI, 26.17-38.57) for mortality. Time-updated VACS Index provided better AMI and mortality prediction than CD4 count and HIV-1 RNA, suggesting that current health determines risk more accurately than prior history and that risk assessment can be improved by biomarkers of organ injury.

Geriatric Assessments and Association With VACS Index Among HIV-Infected Older Adults in San Francisco.

To perform geriatric assessments in older HIV-infected adults in San Francisco and examine the association with age and the Veterans Aging Cohort Study (VACS) index scores. A cross-sectional study was conducted from 2012 to 2014 among HIV-infected patients ≥50 years at 2 San Francisco-based HIV clinics. We evaluated 4 health domains: (1) physical health and function (activities of daily living), instrumental activities of daily living (IADL), falls, gait speed, (2) social support (physical and perceived support, loneliness), (3) mental health (depression, anxiety, posttraumatic stress disorder) and cognition, and (4) behavioral and general health (antiretroviral adherence and quality of life). Contingency table and rank-sum analyses examined associations between these domains with age and VACS index scores. Three hundred fifty-nine patients completed assessments (median age 57; 85% male; 57% white; 72% >high school education). On functional assessment, 39% reported dependence with ≥1 IADL, and 40% reported falls in the previous year. Fifty-eight percent experienced loneliness, 60% the lowest levels of perceived social support, 55% depression, and 12% posttraumatic stress disorder. Forty percent had possible mild cognitive impairment. Thirty percent reported poor or fair quality of life. Older age was associated with lower CD4 counts, balance problems, slower gait, lower anxiety, poorer general health, and higher antiretroviral adherence. VACS Index score was associated with dependence in ≥1 IADL and antiretroviral adherence. In a large sample of older HIV-infected adults, multiple significant aging-related conditions were identified. Integrating geriatric assessment tools into HIV/AIDS clinical care may help target interventions to optimize clinical care and quality of life for older HIV-infected individuals.