An internationally generalizable risk index for mortality after one year of antiretroviral therapy

Abstract

Objective: Despite the success of antiretroviral therapy (ART), excess mortality continues for those with HIV infection. A comprehensive approach to risk assessment, addressing multiorgan system injury on ART, is needed. We sought to develop and validate a practical and generalizable mortality risk index for HIV-infected individuals on ART.

Design and methods: The Veterans Aging Cohort Study (VACS) was used to develop the VACS Index, based on age, CD4 cell count, HIV-1 RNA, hemoglobin, aspartate and alanine transaminase, platelets, creatinine and hepatitis C status, and a Restricted Index based on age, CD4 cell count and HIV-1 RNA with an outcome of death up to 6 years after ART initiation. Validation was in six independent cohorts participating in the ART Cohort Collaboration (ART-CC).

Results: In both the development (4932 patients, 656 deaths) and validation cohorts (3146 patients, 86 deaths) the VACS Index had better discrimination than the Restricted Index (c-statistics 0.78 and 0.72 in VACS, 0.82 and 0.78 in ART-CC). The VACS Index also demonstrated better discrimination than the Restricted Index for HIV deaths and non-HIV deaths, in men and women, those younger and older than 50 years, with and without detectable HIV-1 RNA, and with or without HCV coinfection.

Conclusions: Among HIV-infected patients treated with ART, the VACS Index more accurately discriminates mortality risk than traditional HIV markers and age alone. By accounting for multiorgan system injury, the VACS Index may prove a useful tool in clinical care and research.

Conflict of interest statement

Conflicts of interest: There are no conflicts of interest.

Figures

Fig. 1. All-cause, 5-year mortality rates by risk score

(a) VACS cohort, Restricted Index. (b) ART-CC cohorts, Restricted Index. (c) VACS cohort, VACS Index. (d) ART-CC cohorts, VACS Index. (e) VACS cohort, VACS Index, low risk. (f) ART-CC cohorts, VACS Index, low risk. Low risk: age less than 50, CD4 cell count more than 200 cells/μl, undetectable HIV-1 RNA. ART-CC, antiretroviral therapy cohort collaboration; VACS, Veterans Aging Cohort Study.