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The VACS index predicts mortality in a young, healthy HIV population starting highly active antiretroviral therapy.

ABSTRACT: 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.

SUBMITTER: Bebu I

PROVIDER: S-EPMC4091811 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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The VACS index predicts mortality in a young, healthy HIV population starting highly active antiretroviral therapy.

Bebu Ionut I Tate Janet J Rimland David D Mesner Octavio O Macalino Grace E GE Ganesan Anuradha A Okulicz Jason F JF Bavaro Mary M Weintrob Amy C AC Justice Amy C AC Agan Brian K BK

Journal of acquired immune deficiency syndromes (1999) 20140201 2

<h4>Background</h4>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.<h4>Methods</h4> ...[more]

PMID: 24226058

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Project description:The prevalence of age-related comorbidities is increased in people living with HIV, even in those well-controlled on combination antiretroviral therapy (ART). Persistent immune activation and inflammation may play pivotal roles in the pathogenesis; however, the burden of morbidities in the older HIV infected population may be exacerbated and driven by distinct mechanisms. In a cross sectional study of 45 HIV-infected participants 60 years or older, we examined the relationships between 14 immunomodulatory and inflammatory factors and the Veterans Aging Cohort Study (VACS) Index, a metric of multimorbidity and mortality comprised of age, CD4 count, hemoglobin, Fibrosis-4 [FIB-4], and estimated glomerular filtration rate [eGFR], by linear regression analysis. All participants were virally suppressed (<50 HIV RNA copies/mL), on ART, and primarily Caucasian (86.7%), and male (91.1%). Plasma levels of monocyte/macrophage-associated (neopterin, IP-10, sCD163, sCD14, and MCP-1) and glycan-binding immunomodulatory factors (galectin (Gal)-1, Gal-3, and Gal-9) were assessed, as well as inflammatory biomarkers previously linked to the VACS Index (i.e., CRP, cystatin C, TNF-?, TNFRI, IL-6, and D-dimer) for comparison. In regression analysis, higher VACS index scores were associated with higher levels of neopterin, cystatin C, TNFRI, and Gal-9 (all p < 0.05), potentially driven by correlations found with individual VACS components, including age, CD4 count, FIB-4, and eGFR. Gal-9, cystatin C, and TNFRI directly correlated with the extent of multimorbidity. Multiple correlations among markers were observed, suggesting an interplay of overlapping, but distinct, pathways. Collectively, in addition to cystatin C and TNFRI, both galectin-9 and neopterin, independently emerged as novel fluid markers of the VACS Index and burden of comorbidity and may further guide in understanding pathogenic mechanisms of age-related disorders in older HIV-infected individuals on suppressive ART.

Project description:BackgroundMortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa.Methods and findingsPatients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77).ConclusionsMortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

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The VACS index predicts mortality in a young, healthy HIV population starting highly active antiretroviral therapy.

Publications

The VACS index predicts mortality in a young, healthy HIV population starting highly active antiretroviral therapy.

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