Survival Benefit of Initiating Antiretroviral Therapy in HIV-Infected Persons in Different CD4⁺ Cell Strata

Background: Optimal timing of antiretroviral therapy (ART) initiation for HIV-infected persons remains unclear. Objective: To assess survival benefit of initiating ART at different CD4⁺ cell counts. Design: Prospective observational study. Setting: U.S. clinics in the HIV Outpatient Study (HOPS). Patients: HIV-infected patients with CD4+ cell counts, plasma HIV RNA viral load, and ART use recorded from January 1994 through March 2002. Measurements: Before initiation of ART, patients were grouped by their CD4+ cell counts into three subgroups: 0.201 to 0.350 × 10⁹ cells/L (n = 399), 0.351 to 0.500 × 10⁹ cells/L (n = 327), and 0.501 to 0.750 × 10⁹ cells/L (n = 122). We compared mortality rates for each CD4 ⁺ subgroup among patients who initiated ART and patients who delayed ART until reaching a lower CD4⁺ subgroup. Results: Mortality rates for 340 patients who initiated ART and 59 who delayed ART in the CD4+ subgroup of 0.201 to 0.350 × 10⁹ cells/L were 15.4 and 56.4 deaths per 1000 person-years, respectively (rate ratio, 0.27 [95% CI, 0.14 to 0.55]; P < 0.001). For the CD4⁺ subgroup of 0.351 to 0.500 × 10 ⁹ cells/L, mortality rates for 240 patients who initiated ART and 887 who delayed ART were 10.0 and 16.6 deaths per 1000 person-years, respectively (rate ratio, 0.61 [CI, 0.22 to 1.67]; P = 0.17). For the CD4 ⁺ subgroup of 0.501 to 0.750 × 10⁹ cells/L, mortality rates in 55 patients who initiated ART and 67 who delayed ART were 7. 5 and 3.1 deaths per 1000 person-years, respectively (rate ratio, 1.20 [CI, 0. 17 to 8.53]; P > 0.2). Patients in the 0.201 to 0.350 x 109 cells/L and 0. 351 to 0.500 × 10⁹ cells/L CD4⁺ sub-groups who initiated ART were more likely than those who delayed ART to achieve an undetectable HIV viral load (P = 0.03 and 0.04, respectively). Conclusions: Among HIV-infected persons with CD4⁺ cell counts of 0.201 to 0.350 × 10⁹ cells/L, initiating ART is associated with reduced mortality compared with delaying such therapy. Survival benefits of earlier ART initiation (at CD4⁺ cell counts of 0.351 to 0.500 × 10 ⁹ cells/L) are possible.