The Veterans Aging Cohort Study (VACS) Index Predicts Mortality in a Community-recruited Cohort of People With Human Immunodeficiency Virus (HIV) Who Use Illicit Drugs.
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SUBMITTER: Reddon H
PROVIDER: S-EPMC8496478 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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The Veterans Aging Cohort Study (VACS) Index Predicts Mortality in a Community-recruited Cohort of People With Human Immunodeficiency Virus (HIV) Who Use Illicit Drugs.
Reddon Hudson H Grant Cameron C Nosova Ekaterina E Fairbairn Nadia N Barrios Rolando R Justice Amy C AC Nolan Seonaid S Socias M Eugenia ME Milloy M-J MJ
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20210801 3
The Veterans Aging Cohort Study (VACS) index combines commonly collected clinical biomarkers to estimate human immunodeficiency virus (HIV) disease severity. Among a prospective cohort of people living with HIV who use illicit drugs (PWUD) (n = 948), we found that the VACS index was significantly associated with mortality over a 20-year study period. ...[more]
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Project description:BackgroundHIV is an infectious disease affecting 36.7 million people worldwide. In recent times, Antiretroviral Therapy (ART) has become accessible to the majority of People Living with HIV (PLHIV) and this has transformed the course of infection to one that is chronic, characterized by fewer diseases pathognomonic of AIDS. In view of this, there is a pressing need for better markers, apart from the routine HIV indicators, to detect comorbidities such as Neurocognitive Impairment (NCI). The aim of this study was to find out the association between Veterans Aging Cohort Study (VACS) index and Neurocognitive function in HIV positive patients.MethodsIn our study, we included 97 HIV positive patients and their Neurocognitive function was assessed using a combination of Montreal Cognitive Assessment and Grooved Pegboard Test, while VACS index was calculated using the most recent laboratory values. Binomial Logistics Regression analyses, adjusting for potential confounding variables, was performed to determine the association between VACS score and Neurocognitive Impairment.ResultsWe found that a higher VACS Index was associated with global and domain-wise Neurocognitive impairment (p < 0.01), specifically in the domains of attention (p < 0.01) and fine motor skills (p = 0.01). Our study also showed that among all the VACS components, older age (p = 0.02) and lower hemoglobin (p < 0.01) values were associated with global NCI. After plotting an ROC curve, a VACS cut-off score of 11.00 was identified as it had good sensitivity (87.0%) and specificity (71.4%) in identifying Global NCI.ConclusionOur findings extend prior research on the use of VACS Index to predict global and domain-wise NCI in HIV-positive patients. However, further research with more comprehensive neurocognitive testing is required in our setting before VACS Index can be used as a tool to screen for neurocognitive dysfunction among PLHIV.
| S-EPMC8336242 | biostudies-literature
Project description:BackgroundThe updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)-specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality.MethodsBecause complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age <50 or ≥50 years, race/ethnicity, HIV-1 RNA ≤500 or >500 copies/mL, CD4 count <350 or ≥350 cells/µL, and years 1999-2009 or 2010-2018. Because mortality rates have decreased over time, the final model was limited to 2010-2018.ResultsAmong 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830-.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809-.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups.ConclusionsBased on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.
| S-EPMC9410720 | biostudies-literature
Project description:BackgroundBoth HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF.Methods and resultsVeterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99).ConclusionsOur study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.
| S-EPMC4624488 | biostudies-literature
Project description:BACKGROUND:The Veterans Aging Cohort Study (VACS) index is a weighted combination of age and 8 clinical variables. It has been well correlated with all-cause mortality among HIV-infected patients. The US Military HIV Natural History Study (NHS) cohort provides a different validation population profile, being younger and healthier. A significant portion of the US HIV population is similarly composed; so, evaluation of the VACS index in this population is of great interest. METHODS:NHS subjects have medical history and laboratory data collected at 6-month visits. We performed an external validation of the VACS index in the NHS evaluating correlation, discrimination, and calibration for all-cause mortality after highly active antiretroviral therapy initiation (HI). We then tested whether combining longitudinal VACS index values at different time points improves prediction of mortality. RESULTS:The VACS index at 1 year after HI was well correlated with all-cause mortality (Harrell c statistic 0.78), provided good discrimination (log-rank P < 0.05), and was marginally well calibrated using Brier score. Accounting for VACS index at HI and 6 months after HI significantly improved a standard model, including only the VACS index at 1 year after HI (net reclassification improvement = 25.2%, 95% CI: 10.9% to 48.9%). CONCLUSIONS:The VACS index was well correlated and provided good discrimination with respect to all-cause mortality among highly active antiretroviral therapy initiating subjects in the NHS. Moderate overprediction of mortality in this young, healthy population suggests minor recalibration that could improve fit among similar patients. Considering VACS index at HI and 6 months improved outcome prediction and allowed earlier risk assessment.
| S-EPMC4091811 | biostudies-literature
Project description:BackgroundReal-world data on treatment patterns and clinical outcomes for newer drugs, including integrase strand transfer inhibitors, among older people with human immunodeficiency virus (PWH) are limited.MethodsThis cohort study included PWH enrolled in the Veterans Aging Cohort Study (VACS) who were prescribed a standard 3-drug antiretroviral therapy (ART) regimen containing dolutegravir (DTG), bictegravir (BIC), cobicistat boosted elvitegravir (EVG), raltegravir (RAL), or darunavir/ritonavir (DRV) plus 2 nucleoside reverse transcriptase inhibitors between January 1, 2014, and March 31, 2020, and who were ≥50 years at regimen initiation. The association between regimen and virologic effectiveness or discontinuation was assessed using logistic regression models with inverse probability of treatment weights. Pairwise comparisons were made between DTG-based regimen and each of the other 3-drug regimens, stratified by ART experience.ResultsAmong 15,702 PWH (across treatment groups, median age 58-62 years; 94-98% male; 5-11% Hispanic; 44-60% Black; 29-42% White), 5,800 received DTG-based regimens, 2,081 BIC-based regimens, 4,159 EVG-based regimens, 1,607 RAL-based regimens, and 2,055 received DRV-based regimens. Among ART-naïve PWH, there were no statistical differences in the odds of virologic suppression, and 6- and 12-month discontinuations were higher in those on DRV. Among ART-experienced PWH, compared to DTG, those on RAL and DRV were less likely to be suppressed at 6 months (RAL vs DTG: aOR 0.64, 95% CI 0.51-0.81; DRV vs DTG: aOR 0.63, 95% CI 0.51-0.76) and those on EVG and DRV were less likely suppressed at 12 months (EVG vs DTG: aOR 0.82, 95% CI 0.68-0.99; DRV vs DTG: aOR 0.64, 95% CI 0.52-0.80). Those on DRV were more likely to have virologic failure within 12 months (aOR 1.96, 95% CI 1.30-2.97). Six- and 12-month discontinuations were higher in those on RAL and DRV, but less likely for BIC-based regimens.ConclusionsDTG-based regimens demonstrated higher levels of effectiveness and durability compared to DRV- or RAL-based regimens and had similar treatment responses as BIC- and EVG-based regimens among ART-experienced older PWH.
| S-EPMC11662819 | biostudies-literature
Project description:BackgroundBy supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1-5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups.MethodsWe used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level.ResultsMean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA <500 copies per milliliter (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups.ConclusionsVACS index scores discriminate risk and translate into accurate mortality estimates over 1-5 years of exposure to ART and for diverse patient subgroups from North American.
| S-EPMC3619393 | biostudies-literature
Project description:Human immunodeficiency virus (HIV) infection is associated with subclinical cardiomyopathy, diastolic dysfunction, and increased risk of cardiovascular death. However, the relationship between left atrial (LA) mechanics and left ventricular (LV) diastolic function has not been evaluated in people living with HIV (PLWH) relative to HIV-uninfected (HIV-) controls. This is a multicenter, cross-sectional cohort analysis using the HIV Cardiovascular Disease substudy of the Veterans Aging Cohort Study database, which aimed to examine a cohort of PLWH and HIV- veterans without known cardiovascular disease. A total of 277 subjects (180 PLWH, 97 HIV-) with echocardiograms were identified. LV and LA phasic strain were derived and diastolic function was evaluated. Relationship between LA strain, LV strain, and the degree of diastolic dysfunction were assessed using analysis of variance and ordinal logistic regression with propensity weighting. In the PLWH cohort, 91.7% were on antiretroviral therapy and 86.1% had HIV viral loads <500 copies/ml. The mean (± SD) duration of infection was 9.7 ± 4.9 years. Relative to HIV- veterans, PLWH did not differ in LA mechanics and proportion of diastolic dysfunction (p = 0.31). Using logistic regression with propensity weighting, we found no association between HIV status and degree of diastolic dysfunction. In both cohorts, LA reservoir strain and LA conduit strain were inversely and independently associated with the degree of diastolic dysfunction. Compared with HIV- veterans, PLWH who are primarily virally suppressed and antiretroviral-treated did not differ in LA strain or LV diastolic dysfunction. If confirmed in other cohorts, HIV viral suppression may curtail adverse alterations in cardiac structure and function.
| S-EPMC10193525 | biostudies-literature
Project description:ImportanceWith the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)-infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population.ObjectiveTo examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV.Design, setting, and participantsIncluded in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998-2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015.Main outcomes and measuresIncident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009.ResultsThe mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05-1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04-1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05-1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00-1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87-1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI.Conclusions and relevanceWe report novel evidence that HIV-infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population.
| S-EPMC5621480 | biostudies-literature
Project description:BACKGROUND:The 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). METHODS:We 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. RESULTS:Patients 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. CONCLUSION:Our 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.
| S-EPMC6394994 | biostudies-literature
Project description:BackgroundPredicting cause-specific mortality among people with HIV (PWH) could facilitate targeted care to improve survival. We assessed discrimination of the Veterans Aging Cohort Study (VACS) Index 2.0 in predicting cause-specific mortality among PWH on antiretroviral therapy (ART).MethodsUsing Antiretroviral Therapy Cohort Collaboration data for PWH who initiated ART between 2000 and 2018, VACS Index 2.0 scores (higher scores indicate worse prognosis) were calculated around a randomly selected visit date at least 1 year after ART initiation. Missingness in VACS Index 2.0 variables was addressed through multiple imputation. Cox models estimated associations between VACS Index 2.0 and causes of death, with discrimination evaluated using Harrell's C-statistic. Absolute mortality risk was modelled using flexible parametric survival models.ResultsOf 59 741 PWH (mean age: 43 years; 80% male), the mean VACS Index 2.0 at baseline was 41 (range: 0-129). For 2425 deaths over 168 162 person-years follow-up (median: 2.6 years/person), AIDS (n = 455) and non-AIDS-defining cancers (n = 452) were the most common causes. Predicted 5-year mortality for PWH with a mean VACS Index 2.0 score of 38 at baseline was 1% and approximately doubled for every 10-unit increase. The 5-year all-cause mortality C-statistic was .83. Discrimination with the VACS Index 2.0 was highest for deaths resulting from AIDS (0.91), liver-related (0.91), respiratory-related (0.89), non-AIDS infections (0.87), and non-AIDS-defining cancers (0.83), and lowest for suicides/accidental deaths (0.65).ConclusionsFor deaths among PWH, discrimination with the VACS Index 2.0 was highest for deaths with measurable physiological causes and was lowest for suicide/accidental deaths.
| S-EPMC11249920 | biostudies-literature