Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2014 Mar 25;9(3):e92606.
doi: 10.1371/journal.pone.0092606. eCollection 2014.

The VACS index accurately predicts mortality and treatment response among multi-drug resistant HIV infected patients participating in the options in management with antiretrovirals (OPTIMA) study

Sheldon T Brown  1 , Janet P Tate  2 , Tassos C Kyriakides  3 , Katherine A Kirkwood  3 , Mark Holodniy  4 , Joseph L Goulet  2 , Brian J Angus  5 , D William Cameron  6 , Amy C Justice  2 ; OPTIMA Team
Collaborators, Affiliations
Randomized Controlled Trial

The VACS index accurately predicts mortality and treatment response among multi-drug resistant HIV infected patients participating in the options in management with antiretrovirals (OPTIMA) study

Sheldon T Brown et al. PLoS One. .

Abstract

Objectives: The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study.

Methods: Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel's C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality.

Results: Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14-0.49) and 0.39(95% CI 0.22-0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27-3.38) and 1.51 (95%CI 0.90-2.53) for the 25% least improved scores.

Conclusions: The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Mortality from Randomization Date by Risk Score.
Left: Restricted Index; Right: VACS Index. Upper panels: Kaplan-Meier plots by quartile of score. Plot ends at last death. Lower panels: Mortality at 216 weeks vs. score, Lines: Predicted mortality, Points (95% Confidence Intervals) from Kaplan-Meier estimates using five-point intervals of score (collapsed if necessary to maintain at least 5 deaths and 10 survivors in each interval).
Figure 2
Figure 2. Net Reclassification Improvement (NRI) for Mortality at 216 weeks VACS Index versus Restricted Index.
Groups of predicted risk were made with approximately equal numbers of death using Restricted Index compared to same cut-points using VACS Index. NRI is positive when more deaths have higher predicted risk and more survivors have lower predicted risk. A net 15.5% of those who died were reclassified to a higher risk using the VACS Index and 7.7% of those who lived were reclassified to a lower risk using the VACS Index.
Figure 3
Figure 3. Risk Score by Time on Study (Weeks since Randomization) by Treatment Arm.
See this image and copyright information in PMC

References

    1. Katlama C, Haubrich R, Lalezari J, Lazzarin A, Madruga JV, et al. (2009) Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS 23: 2289–2300 10.1097/QAD.0b013e3283316a5e [doi] - DOI - PubMed
    1. Steigbigel RT, Cooper DA, Teppler H, Eron JJ, Gatell JM, et al. (2010) Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin Infect Dis 50: 605–612 10.1086/650002 [doi] - DOI - PMC - PubMed
    1. Neuhaus J, Angus B, Kowalska JD, La RA, Sampson J, et al. (2010) Risk of all-cause mortality associated with nonfatal AIDS and serious non-AIDS events among adults infected with HIV. AIDS 24: 697–706 10.1097/QAD.0b013e3283365356 [doi] - DOI - PMC - PubMed
    1. El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, et al. (2006) CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 355: 2283–2296 355/22/2283 [pii];10.1056/NEJMoa062360 [doi] - DOI - PubMed
    1. Achhra AC, Amin J, Law MG, Emery S, Gerstoft J, et al. (2010) Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS 24: 1877–1886 10.1097/QAD.0b013e32833b1b26 [doi] - DOI - PMC - PubMed

Publication types