Age at Entry Into Care, Timing of Antiretroviral Therapy Initiation, and 10-Year Mortality Among HIV-Seropositive Adults in the United States

Background. The goal of targeted antiretroviral therapy initiation is to minimize disease progression among patients with human immunodeficiency virus while minimizing the therapeutic burden on these patients. We examine whether the effect of delaying therapy initiation from 500 cells/mm(3) to 350 or 200 cells/mm(3) is modified by age at entry into care. Methods. We used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for therapy initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients 18 to 34, 35 to 44, and 45 to 65 years of age at study entry. Results. In the observed data, 10-year mortality was 13% (165 deaths). Mortality increased from 11% under therapy initiation at 500 cells/mm(3) to 12% at 350 cells/mm3 (risk difference [RD]: 0.87; 95% confidence interval [CI]:.56, 2.17) and to 14% at 200 cells/mm(3) (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying therapy became greater with age: RDs comparing the 350-cells/mm(3) threshold with the 500-cells/mm(3) threshold ranged from -0.03 (95% CI: -0.15, 1.76) for patients 18 to 34 years of age to 0.99 (95% CI: -.27, 1.98) for patients 35 to 44 and to 2.30 (95% CI: 1.29, 5.42) for patients 45 to 65. Conclusions. Delaying therapy increased 10-year mortality in the full cohort. Subgroup analysis highlights that patients entering care at older ages may be more vulnerable to the consequences of delayed ART initiation than younger patients.