Predictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: a North American cross cohort analysis

Abstract

Background: By 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.

Methods: We 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.

Results: Mean 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.

Conclusions: VACS 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.

Figure 1

Observed (Kaplan-Meier estimates) five-year mortality according to index score in 10,835 HIV infected patients after one year of antiretroviral therapy. The I bars denote 95% confidence intervals. Bubble size is proportional to the number of subjects at each data point. (NA-ACCORD Subjects Only)

Figure 2

Predicted mortality by VACS Index score based on 15,901 HIV infected patients with one year of antiretroviral therapy (ART). (NA-ACCORD and VACS Subjects)

Figure 3

Kaplan-Meier estimates of five-year mortality according to VACS Index score after one year of antiretroviral therapy, by subgroup. (NA-ACCORD and VACS Subjects) A. NA-ACCORD (N = 10835), B. VACS (N=5066) C. Men (N = 12785), D. Women (N = 3116), E. Age < 50 years (N = 11191), F. Age >50 years (N = 4710), G. Black (N= 5878), H. White (N = 6079), I. HIV RNA <500 copies/ml (N=8715), J. HIV RNA > 500 copies/ml (N= 7186). The I bars denote the 95% confidence intervals. Solid line is fitted curve for the overall study sample (N = 15901).